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According to the results of our investigation, distinct bacterial isolates capable of breaking down agar were found in various nonmarine environments. The deficiency of reducing sugar in the control media demonstrates that the agar in the experiment is broken down by the bacteria to produce various oligosaccharides because the viscosity of the medium containing the agar was found to have been extremely high before inoculation, reducing with incubation duration and attaining a maximum after 48 hours. These isolates were subsequently used in tests along with additional investigation since they could create reducing sugar. Interestingly, the deterioration of agar appears to be mainly caused by Gram-negative bacteria. In order to study the agarase properties, the relative quantity of the enzyme secreted by the bacteria that hydrolyze the agar was used. The detection of extracellular agarase surrounding the colonies and the absence of stained halos on iodine-treated agar plates show that the agarase diffusing from the bacteria impacted the characteristics of the gel. Inconclusion, these agarsase-producing bacteria can be exploited for industrial applications. Waste agar from the plant tissue culture business can be utilized for a range of applications and this degraded agar can be explored for reliable and ecologically safe alternatives. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE), which entails the formation of a thrombus (blood clot) in a vein, has a significant disease burden worldwide. While VTE has traditionally been considered to predominantly affect Caucasian populations, recent studies have indicated a gradual shift in the disease burden towards Asian populations, with added significance of it being a key driver of post-operative mortality. It is imperative to develop a sound understanding of the various factors that affect VTE in stratified local populations. However, there is a glaring paucity of quality data on VTE and its ramifications among Indians - both in terms of quality of life and cost of healthcare. This review aims to throw light on the disease burden, epidemiology, risk factors, environmental factors, food and nutrition that plays a key role in VTE. We also explored the association of VTE with coronavirus disease 2019 to grasp the interplay between the two most significant public health crises of our time. It is vital to place a special emphasis on future research on VTE in India to plug the gaps, which exist in our current knowledge of the disease, particularly with respect to Indian population. [ABSTRACT FROM AUTHOR]

[Display omitted] Traumatic brain injury (TBI) triggers a bevy of changes including mitochondrial dysfunction, apoptosis, oxidative stress, neurobehavioural impairment, and neuroinflammation, among others. Dantrolene (DNT), a muscle relaxant which inhibits intracellular Ca2+ signaling from the ER, has been repurposed as a potential neuroprotective agent in various neurological diseases. However, there have been limited studies on whether it can mitigate TBI-induced deficits and restore impaired mitochondrial dynamics. This study sought to evaluate whether Dantrolene can potentially provide neuroprotection in an in vivo model of TBI. Male wistar rats subjected to TBI were treated with DNT (10 mg/kg) 1 h and 12 h post surgery. Animals were assessed 24 h post-TBI to evaluate neurobehavioural deficits and cerebral edema. We evaluated the protein expressions of apoptotic, autophagic, and neuroinflammatory markers by immunoblotting, as well as Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) via Flow Cytometry to ascertain the effects of DNT on TBI. We further analysed immunofluorescence staining with Glial Fibrillary Acidic Protein (GFAP) and immunohistochemistry with NF-κβ to investigate neuroinflammation. H&E staining was also performed post-TBI. Our findings revealed DNT administration inhibits mitochondria-mediated apoptotis and reduces heightened oxidative stress. DNT treatment was also found to reverse neurobehavioural impairments and offer neuroprotection by preserving neuronal architechture. We also demonstrated that DNT inhibits neuronal autophagy and alleviates neuroinflammation following TBI by modulating the NF-κβ/Akt signaling pathway. Thus, our results suggest a novel application of DNT in ameliorating the multitude of deficits induced by TBI, thereby conferring neuroprotection. [ABSTRACT FROM AUTHOR]

Background: Piperine (PIP) is a powerful anti-oxidant and anti-inflammatory alkaloid which has been widely used in the treatment of various pathological conditions. However, few studies have clearly discussed the protective effects and potential mechanism of PIP in different neurological diseases. The aim of this study was to investigate the neuroprotective effect of PIP against 3-nitropropioninc acid (3-NP) induced neurobehavioral, biochemical and histopathological alterations in animals. Methods: Adult male Wistar rats were randomly divided into three groups. Group 1, the vehicle administered control group, received normal saline (p.o.). Group 2 received 3-NP (20 mg/kg.b.wt., i.p.) for 4 consecutive days. Group 3 received PIP (10 mg/kg.b.wt., p.o.) twice daily for a period of 4 days, 30 min before and 6 h after the 3-NP injection. Upon termination of treatment schedule, behavioral experiments were performed to access the behavioral outcomes. The brain striatal tissue was used for the estimation of monoamine oxidase activity and serotonin level. In addition, astrocytes activation was observed by GFAP immunostaining. Results: Our results showed that 3-NP induced behavioral impairments are attenuated by PIP co-treatment. Next, the extent of neuronal loss and astrocytes activation was reduced in the striatal brain region in PIP treated rats. Finally, it was observed that PIP alleviated the behavioral, biochemical, immunohistochemical and histological alterations. Conclusion: The results of the current study reveal the neuroprotective competency of PIP against Huntington disease like symptoms in rats. [ABSTRACT FROM AUTHOR]

• Mitochondrial dysfunction has been recognized as a hallmark in ischemia/reperfusion neural damage. • Ropinirole is considered as a promising neurological and functional recovery agent. • Ropinirole restores neurological function and histopathological changes after ischemic injury. • Ropinirole treatment is beneficial in preserving the mitochondrial functions. Stroke is characterized by an initial ischemia followed by a reperfusion that promotes cascade of damage referred to as primary injury. The loss of mitochondrial function after ischemia, which is characterized by oxidative stress and activation of apoptotic factors is considered to play a crucial role in the proliferation of secondary injury and subsequent brain neuronal cell death. Dopamine D2 receptor agonist, Ropinirole, has been found to promote neuroprotection in Parkinson´s disease and restless leg syndrome. The current study was designed to test its efficacy in preclinical model of stroke. Previously it has been demonstrated that Ropinirole mediates its neuroprotection via mitochondrial pathways. Assuming this, we investigated the effect of Ropinirole on mitochondrial dysfunction, we have shown the positive effect of Ropinirole administration on behavioral deficits and mitochondrial health in an ischemic stroke injury model of transient middle cerebral artery occlusion (tMCAO). Male Wistar rats underwent transient middle cerebral artery occlusion and then received the Ropinirole (10 mg and 20 mg/kg b.w.) at 6 h, 12 and 18 h post occlusion. Behavioral assessment for functional deficits included grip strength, motor coordination and gait analysis. Our findings revealed a significant improvement with Ropinirole treatment in tMCAO animals. Staining of isolated brain slices from Ropinirole-treated rats with 2, 3,5-triphenyltetrazolium chloride (TTC) showed a reduction in the infarct area in comparison to the vehicle group, indicating the presence of an increased number of viable mitochondria. Ropinirole treatment was also able to attenuate mitochondrial reactive oxygen species (ROS) production, as well as block the mitochondrial permeability transition pore (mPTP), in the tMCAO injury model. In addition, it was also able to ameliorate the altered mitochondrial membrane potential and respiration ratio in the ischemic animals, thereby suggesting that Ropinirole has a positive effect on mitochondrial bioenergetics. Ropinirole inhibited the translocation of cytochrome c from mitochondria to cytosol reduces the downstream apoptotic processes. In conclusion, these results demonstrate that Ropinirole treatment is beneficial in preserving the mitochondrial functions that are altered in cerebral ischemic injury and thus can help in defining better therapies. [ABSTRACT FROM AUTHOR]

Agar oligosaccharides are thought to be valuable biomolecules with high bioactivity potential, along with a wide range of applications and advantages. The current study aimed to optimize the culture parameters required to produce agarase enzyme and agar oligosaccharides from industrial waste agar. Microbacterium spp. strain SS5 was isolated from a non-marine source and could synthesize oligo derivatives for use in a variety of industries ranging from food to pharmaceuticals. In addition, the strain and culture conditions were optimized to maximize extracellular agarase production. The bacterium grew best at pH 5.0 − 9.0, with an optimal pH of 7.5 − 8.0; temperatures ranging from 25 to 45 °C, with an optimal of 35 °C; and carbon and nitrogen concentrations of 0.5% each. Plackett-Burman experimental design and response surface methods were used to optimize various process parameters for agarase production by Microbacterium spp. strain SS5. Using the Plackett-Burman experimental design, eleven process factors were screened, and agar, beef extract, CaCl2, and beginning pH were found as the most significant independent variables affecting agarase production with confidence levels above 90%. To determine the optimal concentrations of the identified process factors on agarase production, the Box- Behnken design was used. Agarase production by Microbacterium spp. strain SS5 after optimization was 0.272 U/mL, which was determined to be greater than the result obtained from the basal medium (0.132 U/mL) before screening using Plackett-Burman and BBD with a fold increase of 2.06. [ABSTRACT FROM AUTHOR]

Memories are acquired and stored in two forms, short-term memory (STM) and long-term memory (LTM). For the consolidation of LTM, de novo protein synthesis is required, which are also known as plasticity related proteins. Long-term potentiation is a form of synaptic plasticity and it is considered as a cellular model of learning and memory. One of the Long-term potentiation specific plasticity related proteins, PKM-ζ, is required for the formation of LTM as well as for the maintenance of Long-term potentiation. In our study, we have shown that for the consolidation of LTM, in addition to Long-term potentiation -specific plasticity related proteins, synaptic tags are required to interact with each other. In the present study, we investigated the involvement of Long-term potentiation -specific PKM-ζ and learning tags within a critical time window, which are required for the formation of LTM without affecting STM. Behavioral tagging is an established model for the assessment of some forms of learning and memory. Despite being studied for LTM formation for many years, no studies so far have investigated the role of PKM-ζ in Behavioral tagging model. Hence, by using these two different memories based tasks (i.e., Inhibitory avoidance and Novel object recognition tasks), we observed how PKM-ζ activated by exposing a novel arena after a weak training and led to the consolidation of memory. These findings thus show how the process of behavioral tagging activates Long-term potentiation -specific PKM-ζ for the formation of LTM. • For the establishment of LTM protein synthesis is required. • PRP's are captured in the activated learning tags set during the learning session. • PKM-ζ plays an important role as a LTP-specific PRP in behavior tagging. • Up-regulation of PKM-ζ mRNA leads to the consolidation of long term memory. • Expression of PKM-ζ in contributes to formation of novel object recognition memory. [ABSTRACT FROM AUTHOR]

Nigella sativa L. belonging to Ranunculaceae family is an important medicinal spice which has been utilised to treat various chronic diseases. Lipid nanoemulsions containing oil from medicinal plants have shown to enhance drug dissolvability, diminish symptoms of different powerful medications and enhance the bioavailability of medications, in contrast with conventional formulations. In the present study, aqueous titration method was used to prepare nanoemulsion. The optimised formulation (NE11) with the mean particle size of 37.47 nm showed a minimum viscosity of 0.547 cps and maximum drug release (98.2%) in 24 h. The stability study showed considerably stable formulations at refrigerator temperature as compared to room temperature. The cancer cell line studies confirmed that 5d sprout extract of N. sativa nanoemulsion reduced the cell viability (p < .05) and increased colony formation, ROS intensity and chromatin condensation. All data such as colony formation, ROS intensity and chromatin condensation are represented as mean ± SD (p < .001) treated cells for 48 hours. Our results concluded that the development of nanoemulsion could be an efficient carrier for drug delivery. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the hepatoprotective effects of the bioflavonoid quercetin (QR) on cisplatin (CP)‑induced mitochondrial oxidative stress in the livers of rats, to elucidate the role of mitochondria in CP‑induced hepatotoxicity, and its underlying mechanism. Isolated liver mitochondria were incubated with 100 µg/ml CP and/or 50 µM QR in vitro. CP treatment triggered a significant increase in membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, and a decrease in reduced glutathione (GSH) and non‑protein thiol (NP‑SH) levels. In addition, CP caused a marked decline in the activities of enzymatic antioxidants and mitochondrial complexes (I, II, III and V) in liver mitochondria. QR pre‑treatment significantly modulated the activities of enzymatic antioxidants and mitochondrial complex enzymes. Furthermore, QR reversed the alterations in LPO and PC levels, and GSH and NP‑SH contents in liver mitochondria. The results of the present study suggested that QR supplementation may suppress CP‑induced mitochondrial toxicity during chemotherapy, and provides a potential prophylactic and defensive candidate for anticancer agent‑induced oxidative stress. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), an acquired brain injury imparted by a mechanical trauma to the head, has significant ramifications in terms of long-term disability and cost of healthcare. TBI is characterized by an initial phase of cell death owing to direct mechanical injury, followed by a secondary phase in which neuroinflammation plays a pivotal role. Activation of inflammasome complexes triggers a cascade that leads to activation of inflammatory mediators such as caspase-1, Interleukin (IL)-18, and IL-1β, eventually causing pyroptosis. NLRP3 inflammasome, a component of the innate immune response, has been implicated in a number of neurodegenerative diseases, including TBI. Recent findings indicate that NLRP3 inhibitors can potentially ameliorate neuroinflammation and improve cognition and motor function in TBI. The NLRP3 inflammasome also holds potential as a predictive biomarker for the long-term sequelae following TBI. Although several therapeutic agents have shown promising results in pre-clinical studies, none of them have been effective in human trials for TBI, to date. Thus, it is imperative that such promising therapeutic candidates are evaluated in clinical trials to assess their efficacy in alleviating neurological impairments in TBI. This review offers an insight into the pathophysiology of TBI, with an emphasis on neuroinflammation in the aftermath of TBI. We highlight the NLRP3 inflammasome and explore its role in the neuroinflammatory cascade in TBI. We also shed light on its potential as a prospective biomarker and therapeutic target for TBI management. [Display omitted] • Traumatic brain injury (TBI) is an acquired brain injury induced by an external trauma to the head. • Despite causing high mortality rates and significant healthcare costs, there exists no effective therapy for TBI. • NLRP3 inflammasome triggers the activation of several inflammatory mediators like caspase-1, IL-18, and IL-1β. • Recent findings indicate that NLRP3 inhibitors can potentially ameliorate neuroinflammation in the wake of TBI. • NLRP3 inflammasome also holds potential as a predictive biomarker for the long-term sequelae following TBI. [ABSTRACT FROM AUTHOR]

Nonylphenol (NP), an environmental endocrine disruptor mimics estrogen and is a potential toxicant both under in vitro and in vivo conditions. In this study, the effect of melatonin on NP- induced neurotoxicity and cognitive alteration was investigated in adult male Wistar rats. Melatonin supplementation has been known to protect cells from neurotoxic injury. The animals were divided into three groups namely, control (vehicle) which received olive oil orally and treated rats received NP (25 mg/kg, per os ) thrice a week for 45 days while the third group i.e., NP + melatonin, animals were co-administered melatonin (10 mg/kg, i.p. ) along with NP. On the 46th day, rats were assessed for anxiety, motor co-ordination, grip strength and cognitive performance using Morris water maze test and then sacrificed for biochemical and histopathological assays in brain tissues. Melatonin improved the behavioral performance in NP exposed group. The results showed that NP significantly decreased the activity of acetylcholine esterase (AchE), monoamine oxidase (MAO) and Na + /K + -ATPase, in rat brain tissue along with other enzymes of antioxidant milieu. The outcome of the study shows that NP, like other persistent endocrine disrupting pollutants, creates a potential risk of cognitive, neurochemical and histopathological perturbations as a result of environmental exposure. Taken together, our study demonstrates that melatonin is protective against NP-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Among the neurodegenerative diseases (ND), Parkinson's disease affects 6.3 million people worldwide characterized by the progressive loss of dopaminergic neurons in substantia nigra. The mitochondrial permeability transition pore (mtPTP) is a non-selective voltage-dependent mitochondrial channel whose opening modifies the permeability properties of the mitochondrial inner membrane. It is recognized as a potent pharmacological target for diseases associated with mitochondrial dysfunction and excessive cell death including ND such as Parkinson's disease (PD). Imbalance in Ca concentration, change in mitochondrial membrane potential, overproduction of reactive oxygen species (ROS), or mutation in mitochondrial genome has been implicated in the pathophysiology of the opening of the mtPTP. Different proteins are released by permeability transition including cytochrome c which is responsible for apoptosis. This review aims to discuss the importance of PTP in the pathophysiology of PD and puts together different positive as well as negative aspects of drugs such as pramipexole, ropinirole, minocyclin, rasagilin, and safinamide which act as a blocker or modifier for mtPTP. Some of them may be detrimental in their neuroprotective nature. [ABSTRACT FROM AUTHOR]

There is increasing recognition of the magnitude of mitochondria in neurodegenerative disorders. Mitochondria play a key role in apoptotic and necrotic cell death. Melatonin (Mel), an indoleamine produced in several organs including the pineal gland has been known for its neuroprotective actions. In our study, we have investigated whether the mitochondrial ATP sensitive potassium (mtK ATP ) channel blocker 5-hydroxydecanoate (5-HD) and calcium (Ca 2 + ) affects permeability transition pore (PTP) alterations in isolated brain mitochondria treated with melatonin (Mel) and cyclosporin A (CsA). Mitochondrial swelling, mitochondrial membrane potential (Δψ m ), ROS measurement and mitochondrial respiration were evaluated in isolated brain mitochondria. In our results, mitochondrial swelling stimulated by exposing Ca 2 + ions and 5-HD associated by mPTP opening as depicted by modulation of CsA and Mel. In addition, Ca 2 + and 5-HD decreased Δψ m , depleted intracellular ROS, and inhibition of mitochondrial respiration (state 3 and state 4) in isolated brain mitochondria. Addition of Mel and CsA has shown significant restoration in mitochondrial swelling, Δψ m , intracellular ROS measurement and mitochondrial respiration in isolated brain mitochondria. Therefore, we speculate the modulatory effect of Mel and CsA in mitochondria treated with 5-HD and Ca 2 + hinders the mPTP-mediated mitochondrial dysfunction and cellular oxidative stress. We conclude that inhibition of mPT is one likely mechanism of CsA's and its neuroprotective actions. Development of neuroprotective agents including Mel targeting the mPTP therefore bears hope for future treatment of severe neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Neurotoxicity is a burdensome consequence of platinum-based chemotherapy that neutralizes the administration of effective dosage and often prompts treatment withdrawal. Oxaliplatin (Oxa), a third-era platinum analogue that is active against both early-organize and progressed colorectal growth, produces critical neurotoxicity. It has been reported that the Melatonin (Mel) is a pineal hormone its metabolites display important antioxidant properties in nervous system. There is dearth of literature involving the role of mitochondria and cytosolic compartments mediated Oxa-induced neurotoxicity and its underlying mechanisms are still debatable. Rats were pre-treated with Mel (10 mg/kg b.wt., i.p. ) and treated with Oxa (4 mg/kg b.wt. i.p. ) for 5 consecutive days. For neurobehavioral performances, decreased locomotor activity and muscular strength were observed in rats. Treatment with Mel in Oxa treated rats could protect the Oxa induced alterations in motor activity and muscular strength. For painful neuropathy, thermal hyperalgesia/nociceptive tests were evaluated. In addition, pre-treatment of Mel could block or alter the inactivation of Bcl-2, caspase 3 apoptotic protein and alterations Cytochrome c (Cyt c) release in an Oxa rich environment. Pre-treatment of Mel have shown an alteration in hyperalgesia behaviour in Oxa treated rats. Oxidative stress biomarkers, levels of non-enzymatic antioxidants and mitochondrial complexes were evaluated against neurotoxicity induced by Oxa. Mel pre-treatment replenished the mitochondrial lipid peroxidation levels and protein carbonyl content induced by Oxa. Mel also modulated altered non-enzymatic, enzymatic antioxidants and complex enzymes of mitochondria. Futures studies are also required to identify other molecular markers involved in neurotoxicity induced by Oxa and possible action of Mel in its modulation. [ABSTRACT FROM AUTHOR]

Fungicides are a pesticide that particularly kills or destroy fungi responsible for several diseases associated to humans and other living organisms. Assessment of toxic effects and mechanisms of fungicide action is important because humans and domesticated animals get exposed to these pesticides through a wide variety of applications. Several fungicides are being used at the large scale for the crop protection from the fungal invasion. Propiconazole (PCZ), a trazole-containing fungicide, is widely used in China and various Asian countries for food crop protection which made it easily to exposed to the aquatic system. Long term usage of PCZ may contaminate the water bodies, but its toxicity to aquatic organisms is not well studied. In this study, freshwater fish, Channa punctata Bloch was exposed to different sub-lethal concentrations of the fungicide, PCZ (0.5 and 5 ppm) for a period of 96 h. Various biochemical assays and histological alterations were measured to determine the organ toxicity caused by PCZ exposure particularly in liver, kidney and gills of the fishes. Compared to the control group, fish exposed to PCZ (96 h) showed marked dose dependent toxicity. The levels of lipid peroxidation (LPO) and protein carbonyls (PC), oxidative stress biomarker of liver, kidney and gills in the experimental group were significantly higher ( P < 0.05 and P < 0.001) compared to the control group. Levels of reduced glutathione (GSH) and non-protein thiols (NP-SH) decreased significantly ( P <0.05–0.001) in all analyzed intoxicated organs of the PCZ exposed fishes. Activity of glutathione-S-transferase (GST), glutathione peroxidase (GPx) and catalase (CAT) in fungicide treated groups was significantly lowered ( P < 0.05–0.001). In addition, histopathological examination in the organs showed significant changes like atrophy of primary and secondary gill lamellae, infiltrations, inflammation, hepatocyte degeneration, vacuolization and necrotic kidney. Thus, PCZ exposure altered the oxidative stress homeostasis and brought about histopathological changes which may serve as potential biomarkers of the PCZ toxicity in the laboratory set-up for potential risk assessment. [ABSTRACT FROM AUTHOR]

Our study was designed to evaluate effects of an herbicide, pendimethalin on biochemical biomarkers and histopathological indices of the freshwater fish Channa punctata Bloch. Fish were acutely exposed (96 h) to sub-lethal concentrations (0.5 and 0.8 ppb of pendimethalin). Various oxidative stress indicators such as thiobarbituric acid reactive substances levels and protein carbonyl content, as well as antioxidant defenses parameters, such as glutathione-S-transferase (GST), catalase (CAT), reduced glutathione (GSH) and non-protein thiols (NP-SH) levels were studied, using the liver, kidney and gill tissues. Pendimethalin exposure increased lipid peroxidation and protein oxidation processes. There was significant inhibition in levels of GSH and NP-SH. The activity of antioxidant enzymes GST and CAT depleted in all the tissues in a dose dependent manner. The histopathological change in the gill showed necrosis and atrophy of primary and secondary gill lamellae. The tissue damages like degeneration of cytoplasm in hepatocytes, atrophy, formation of vacuoles, are some histopathological changes observed in the liver. The changes in histoarchitechture observed in the kidney included necrosis, cellular hypertrophy and granular cytoplasm. The present study demonstrates the disturbances in antioxidant armamentarium and importance of study in the potential risk assessment of herbicides on fish species. [ABSTRACT FROM AUTHOR]

Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50 mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat. [ABSTRACT FROM AUTHOR]

Fungicides are a class of pesticides which are used indiscriminately in large amounts and pose a serious threat to the environment. Propiconazole (PCZ) is a systemic foliar fungicide with a broad range of activity. The potential of this fungicide to induce toxicity has not been fully explored. The present study was designed to investigate the dose dependent neurotoxic effect of propiconazole (PCZ), with Channa punctata Bloch as a model organism. Effect of PCZ on the brain specific enzyme activity such as acetylcholinesterase (AChE), monoamine oxidase (MAO) and Na + -K + -ATPase was determined in the fish brain tissue exposed to sub-lethal concentrations (0.5 and 5 ppm) for 96 h. Also, levels of oxidative stress reflected by various enzymatic and non-enzymatic antioxidants were measured. Neurotransmitter (epinephrine) level was also assessed. PCZ exposure induced oxidative stress as reflected by the significant increase in fish brain lipid peroxidation and protein carbonyl content with decrease in reduced glutathione levels, as well as the significant inhibition of glutathione dependent metabolizing enzymes and CAT activities. In addition, AChE, MAO and Na + -K + -ATPase activities were significantly lowered along with reduction in epinephrine levels in PCZ exposed fishes than those of the control in a dose dependent manner. Also, histopathological alterations were observed in fish brain of the treated fishes. The results point towards the potential neurotoxicity in the fish caused by PCZ exposure but the application of these findings will need more detailed study before they can be established as special biomarkers for toxicity monitoring the aquatic environment. [ABSTRACT FROM AUTHOR]

Over the years, indiscriminate usage of pesticides has resulted in situations which are not conducive for a good environment. In aquatic toxicology, fishes have been developed as established models for studying toxic responses of xenobiotics including pesticides. Pendimethalin (PD), an herbicide, is widely present in the aquatic environment, but little is known regarding its potential neurotoxicity in fish. The present study was conducted on Channa punctata Bloch exposed to sub-lethal doses of PD (0.5 and 0.8 ppb) for 96 h. The exposure resulted in alterations in epinephrine levels in the fish brain. Epinephrine levels decreased significantly in a dose dependent manner with increase in the PD exposure. A marked decrease in the activity of acetylcholinesterase along with reduction in Na + -K + -ATPase and monoamine oxidase activity was also observed. In comparison with the corresponding controls, the sub-lethal doses of PD also caused significant changes in the oxidative stress markers (lipid peroxidation and carbonyl derivatives of protein oxidative destruction levels) and antioxidant defenses (reduced glutathione levels, catalase, glutathione-s-transferase activity) in brain tissue. Our results reflect that a detailed investigation is warranted regarding the toxicity potential of PD. [ABSTRACT FROM AUTHOR]

Background and Aims Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. Methods The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Results Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Conclusion Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. [ABSTRACT FROM AUTHOR]

The major challenge in today's world is that medical research is facing the existence of a vast number of viruses and their mutations, which from time to time cause outbreaks. Also, the continuous and spontaneous mutations occurring in the viruses and the emergence of resistant virus strains have become serious medical hazards. So, in view of the growing number of diseases, like the recent COVID-19 pandemic that has caused the deaths of millions of people, there is a need to improve rapid and sensitive diagnostic strategies to initiate timely treatment for such conditions. In the cases like COVID-19, where a real cure due to erratic and ambiguous signs is not available, early intervention can be life-saving. In the biomedical and pharmaceutical industries, nanotechnology has evolved exponentially and can overcome multiple obstacles in the treatment and diagnosis of diseases. Nanotechnology has developed exponentially in the biomedical and pharmaceutical fields and can overcome numerous challenges in the treatment and diagnosis of diseases. At the nano stage, the molecular properties of materials such as gold, silver, carbon, silica, and polymers get altered and can be used for the creation of reliable and accurate diagnostic techniques. This review provides insight into numerous diagnostic approaches focused on nanoparticles that could have been established for quick and early detection of such diseases. [ABSTRACT FROM AUTHOR]

Ischemic reperfusion (I/R) injury causes a wide array of functional and structure alternations of mitochondria, associated with oxidative stress and increased the severity of injury. Despite the previous evidence for N -acetyl-L-cysteine (NAC) provide neuroprotection after I/R injury, it is unknown to evaluate the effect of NAC on altered mitochondrial autophagy forms an essential axis to impaired mitochondrial quality control in cerebral I/R injury. Male wistar rats subjected to I/R injury were used as transient Middle Cerebral Artery Occlusion (tMCAO) model. After I/R injury, the degree of cerebral tissue injury was detected by infarct volume, H&E staining and behavioral assessment. We also performed mitochondrial reactive oxygen species and mitochondrial membrane potential by flow cytometry and mitochondrial respiratory complexes to evaluate the mitochondrial dysfunction. Finally, we performed the western blotting analysis to measure the apoptotic and autophagic marker. We found that NAC administration significantly ameliorates brain injury, improves neurobehavioral outcome, decreases neuroinflammation and mitochondrial mediated oxidative stress. We evaluated the neuroprotective effect of NAC against neuronal apoptosis by assessing its ability to sustained mitochondrial integrity and function. Further studies revealed that beneficial effects of NAC is through targeting the mitochondrial autophagy via regulating the GSK-3β/Drp1mediated mitochondrial fission and inhibiting the expression of beclin-1 and conversion of LC3, as well as activating the p-Akt pro-survival pathway. Our results suggest that NAC exerts neuroprotective effects to inhibit the altered mitochondrial changes and cell death in I/R injury via regulation of p-GSK-3β mediated Drp-1 translocation to the mitochondria. [ABSTRACT FROM AUTHOR]

ABSTRACT Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ('behavioral LTP-reinforcement'). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for leukemia and other malignancies. The purpose of this study was to investigate the damage caused by MTX on liver mitochondria and its protection by using antioxidant properties of lipoic acid. MTX substantially affects mitochondrial function by reducing glutathione levels leading to disturbances in antioxidant enzyme defense system. Lipoic acid occurs naturally in mitochondria as a coenzyme. In various studies lipoic acid has been convincingly shown to exhibit an antioxidant role when supplemented exogenously. We studied the effect of lipoic acid pre-treatment on the toxicity of MTX in mouse liver mitochondria focusing specifically on the oxidative stress. MTX caused a significant rise in the mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) content and superoxide radical generation. It also affected the mitochondrial thiol profile. Pre-treatment of mice with lipoic acid (35mg/kg) markedly lowered mitochondrial LPO, PC content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that lipoic acid has a potential role in suppressing MTX-induced mitochondrial toxicity, and it affords protection either by reversing the decline of antioxidants or by the directly scavenging the free radicals. [Copyright &y& Elsevier]

Tamoxifen is a selective oestrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen potentially affects mitochondrial functions as it acts as an uncoupling agent and a powerful inhibitor of mitochondrial electron transport chain. There is concern for the deleterious effects of tamoxifen. Taurine is known to have membrane stabilizing and antioxidant properties. We studied effect of taurine pre-treatment on the toxicity of tamoxifen in mouse liver mitochondria focusing specifically on the redox cycle biomarkers. Tamoxifen caused a significant rise in the mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. There was a significant change in the mitochondrial thiol profile in the tamoxifen-treated animals. Pre-treatment of mice with taurine (100 mg/kg) markedly lowered mitochondrial lipid peroxidation, protein carbonyl content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that taurine has a potential role in ameliorating tamoxifen-induced mitochondrial toxicity, and the protection is afforded either by reversing the decline of antioxidants or by the direct free radical-scavenging activity. [ABSTRACT FROM AUTHOR]

Tamoxifen (TAM) is an anti-neoplastic drug used for the treatment of breast cancer. It decreases the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in cells leading to tissue injury. The present study was undertaken to investigate modulatory effects of taurine on the nephrotoxicity of TAM with special reference to protection against disruption of nonenzymatic and enzymatic antioxidants. Oxidative stress was measured by renal lipid peroxidation (LPO) level, protein carbonyl (PC) content, reduced glutathione (GSH), activities of phase I and II drug metabolizing and antioxidant enzymes. TAM treatment resulted in a significant (P < 0.001) increase in LPO in kidney tissues s compared to control, while taurine pretreatment showed a significant decrease (P < 0.01) in the LPO in kidneys when compared with the TAM-treated group. Taurine + TAM group animals showed restoration in the level of cytochrome P450 content, activities of glutathione metabolizing enzymes viz., glutathione-S-transferase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase. Pretreatment of animals with taurine markedly attenuated, PC content, restored the depleted nonenzymatic and enzymatic antioxidants. These results clearly demonstrate the role of oxidative stress, and suggest a protective effect of taurine on TAM-induced nephrotoxicity in mice. [ABSTRACT FROM AUTHOR]

Abstract: Natural antioxidants like catechin are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from toxic metabolic actions of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an etiological role in anticancer drug-induced toxicity. This study was performed to explore the modulatory and protective effect of catechin on the toxicity of an anticancer drug, tamoxifen (TAM) with special reference to protection against disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment resulted in a significant increase in the lipid peroxidation (LPO), H2O2 generation and protein carbonyl (PC) contents in the liver and kidney as compared to controls while catechin+TAM-treated group showed significant decrease in LPO levels, H2O2 generation and PC contents in liver and kidney when compared with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH) and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due to exogenous catechin administration. Catechin pre-treatment showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated animals. The results of the study show that catechin supplementation might be helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes it a prophylactic and preventive agent of anticancer drug-induced oxidative stress. [Copyright &y& Elsevier]

Abstract: Background: One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine on the toxicity of the anticancer drug tamoxifen with special reference to protection against disruption of drug metabolizing and antioxidant enzymes in Swiss albino mice. Methods: Male Swiss albino mice were divided into 4 groups. The extent of lipid peroxidation was evaluated in terms of thiobarbituric acid reactive substances formed. The following assays were performed in the hepatic tissue (a) antioxidant enzymes such as superoxide dismutase and catalase, (b) cytochrome P450 content, (c) glutathione-metabolizing enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose 6-phosphate dehydrogenase, and (d) low molecular weight antioxidants (reduced glutathione, ascorbic acid) and protein carbonyl content. Results: Tamoxifen induced lipid peroxidation, protein carbonyl content and inhibited the enzymes of antioxidant defense system. It was also observed that the activities of antioxidant enzymes and glutathione-metabolizing enzymes were considerably stabilized in mice pretreated with taurine. Conclusion: Taurine protects the integrity of the hepatic tissue by stabilizing the reactive oxygen species mediated lipid peroxidation and protein carbonyl formation. Additionally taurine may prove to be efficacious as an antioxidant in tamoxifen-induced hepatotoxicity. [Copyright &y& Elsevier]

Excessive mitochondrial fission has been implicated in the etiology of neuronal cell death in traumatic brain injury (TBI). In the present study, we examined the efficacy of melatonin (Mel) as a neuroprotective agent against TBI-induced oxidative damage and mitochondrial dysfunction. We assessed the impact of Mel post-treatment (10 mg/kg b.wt., i.p.) at different time intervals in TBI-subjected Wistar rats. We found that the Mel treatment significantly attenuated brain edema, oxidative damage, mitochondrial fission, and promoted mitochondrial fusion. Additionally, Mel-treated rats showed restoration of mitochondrial membrane potential and oxidative phosphorylation with a concomitant reduction in cytochrome-c release. Further, Mel treatment significantly inhibited the translocation of Bax and Drp1 proteins to mitochondria in TBI-subjected rats. The restorative role of Mel treatment in TBI rats was supported by the mitochondrial ultra-structural analysis, which showed activation of mitochondrial fusion mechanism. Mel enhanced mitochondrial biogenesis by upregulation of PGC-1α protein. Our results demonstrated the remedial role of Mel in ameliorating mitochondrial dysfunctions that are modulated in TBI-subjected rats and provided support for mitochondrial-mediated neuroprotection as a putative therapeutic agent in the brain trauma. [ABSTRACT FROM AUTHOR]

Stroke is one of the main causes of mortality and disability in most countries of the world. The only way of managing patients with ischemic stroke is the use of intravenous tissue plasminogen activator and endovascular thrombectomy. However, very few patients receive these treatments as the therapeutic time window is narrow after an ischemic stroke. The paucity of stroke management approaches can only be addressed by identifying new possible therapeutic targets. Mitochondria have been a rare target in the clinical management of stroke. Previous studies have only investigated the bioenergetics and apoptotic roles of this organelle; however, the mitochondrion is now considered as a key organelle that participates in many cellular and molecular functions. This review discusses the mitochondrial mechanisms in cerebral ischemia such as its role in reactive oxygen species (ROS) generation, apoptosis, and electron transport chain dysfunction. Understanding the mechanisms of mitochondria in neural cell death during ischemic stroke might help to design new therapeutic targets for ischemic stroke as well as other neurological diseases. [ABSTRACT FROM AUTHOR]

Well known as the center for learning and memory, hippocampus is the crucial brain region to study synaptic plasticity in the context of cellular fundamental mechanisms such as long‐term depression (LTD) and long‐term potentiation (LTP). However, despite years of extensive research, the key to our LTD queries and their induction mechanisms has not been fully understood. Previously, we reported the induction of late‐LTD (L‐LTD) in the distally located synapses of apical branch of hippocampal CA1 dendrites using strong low‐frequency stimulation (SLFS). In contrast synapses at the proximal site could not express L‐LTD. Thus, in the present study, we wanted to investigate whether or not synapses of apical dendritic branch at the proximal location could induce and maintain LTD and its related properties in in vitro rat hippocampal slices. Results indicated that the SLFS in the distal and proximal region triggered the plasticity related proteins (PRP) synthesis in both regions, as evident by the induction and maintenance of L‐LTD in the distal region by virtue of synaptic and cross‐tagging. In addition, the application of emetine at the time of proximal input stimulation prevented the transition of early‐LTD (E‐LTD) into L‐LTD at the distal region, proving PRP synthesis at the proximal site. Further, it was observed that weak low‐frequency stimulation (WLFS) could induce E‐LTD in the proximal region along with LTD‐specific tag‐setting at the synapses. In conclusion, the current study suggests unique findings that the synaptic and cross‐tagging mediate L‐LTD expression is maintained in the proximal location of hippocampus apical CA1 dendrites. [ABSTRACT FROM AUTHOR]

Background and Aims To explore hepatoprotective action of curcumin (CMN, a bioflavonoid) on oxaliplatin (Oxa)-triggered mitochondrial oxidative stress and respiratory chain complexes in liver of rats. Oxa is a ubiquitously utilized platinum-based chemotherapeutic agent commonly used for the treatment of colorectal cancer. Mitochondria have recently emerged as targets for anticancer drugs in several kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. There is a dearth of evidence involving the role of mitochondria in mediating Oxa-evoked hepatotoxicity and its underlying mechanism is still debatable. Methods The study was performed in mitochondria isolated from liver of Wistar rats. Oxa (200 μg/mL) and CMN (5 μmol) were incubated under in vitro conditions. Results Oxa evoked a significant increase in the membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, decrease in reduced glutathione (GSH) and nonprotein thiol (NP-SH) levels. Oxa also caused a marked decline in the activities of enzymatic antioxidants and respiratory chain enzymes (I, II, III and V) in liver mitochondria. CMN pre-treatment significantly prevented the activities of enzymatic antioxidants and mitochondrial respiratory chain enzymes. CMN also restored the LPO and PC contents, GSH and NP-SH levels in liver mitochondria. Conclusion CMN intake might be effective in regulation of Oxa-evoked mitotoxicity during chemotherapy. Moreover, it is included in the armamentarium for anticancer agent-induced oxidative stress. [ABSTRACT FROM AUTHOR]

Naringenin is a powerful antioxidant and anti-inflammatory flavonoid which has been widely used as a therapeutic agent in various toxic models. However, few studies have clearly discussed the neuromodulatory effects of naringenin against different neurodegenerative disorders. We investigated the neuroprotective efficacy of naringenin against 3-nitropropionic acid (3-NP)-induced neurobehavioral, biochemical and histopathological alterations in rats. Albino Wistar rats were randomly divided into three experimental groups. Group 1, the vehicle administered group, received saline. Group 2 received 3-NP (20 mg/kg body weight, i.p.) for 4 consecutive days. Group 3 received naringenin (50 mg/kg body weight, p.o.) twice daily for a period of 4 days, 30 min before and 6 h after the 3-NP administration. On the 5th day, neurobehavioral experiments were performed to access the behavioral outcomes and the striatum tissue was used for analysis of the monoamine oxidase (MAO) activity and serotonin (5-HT) levels. In addition, astrocytes activation was observed by glial fibrillary acidic protein (GFAP) immunostaining. Our results showed that naringenin co-treatment provides neuroprotection against 3-NP-induced neurological disorders. Naringenin also increased the MAO activity and 5-HT levels in the striatum. Moreover, co-treatment with naringenin reduced the expression of GFAP protein in the striatal part and significantly attenuated the neuronal cell death. The findings of the present study suggest that naringenin provides neuroprotection and mitigates neurobehavioral alterations in experimental rats. The results show that co-treatment with naringenin ameliorates 3-NP-induced HD-like symptoms in rats. [ABSTRACT FROM AUTHOR]

Context: Chemotherapy has long been the keystone of cancer regimen, and comprehensive research has been done on the development of more potent and less toxic anti-cancer agents. Cisplatin (CP) is a potent and extensively used chemotherapeutic agent. There is paucity of literature involving role of mitochondria in mediating CP-induced hepatic toxicity, and its underlying mechanism remains unclear. Oxidative stress is a well-established biomarker of the mitochondrial toxicity.Objective: This study evaluates the dose-dependent effects of CP-induced mitotoxicity underin vitroconditions, using mitochondria from rat liver.Materials and methods: The aim of our study was to determine the effect of CP with different concentrations in isolated liver mitochondria as anin vitromodel.Results: CP exposure showed significantly compromised level of non enzymatic and enzymatic antioxidants with higher extent of lipid and protein oxidation. CP also caused significant alterations in the activity of respiratory chain enzymes (complex I–III and V) in liver mitochondria.Discussion and conclusion: It is suggested that mitochondria can be employed as a model for future investigations of anticancer drug-induced hepatotoxicity underin vitroconditions. Studies with selected pharmaceuticals and nutraceuticals might certainly play a definite role in deciphering cellular and molecular mechanisms of CP-induced hepatotoxicity and its amelioration. [ABSTRACT FROM PUBLISHER]

Stroke is one of the most devastating neurological disabilities and brain’s vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. [ABSTRACT FROM AUTHOR]

Huntington disease (HD) is an autosomal dominant inheritance neurodegenerative disorder. 3-Nitropropanoic acid (3-NP) is a mitochondrial toxin that induces HD-like symptoms and thus serves as a good experimental model of HD. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid that have multiple biological activities. The present work was aimed to evaluate the neuroprotective efficacy of Chrysin in rat brain, under the influence of 3-NP treatment, by studying neurobehavioral and biochemical alterations alongwith histo-architectural changes. Male Wistar rats (220–250 g) were used in the study and were divided into three groups following randomization. Each group comprised of nine animals. Group I animals served as control group and administered with normal saline (orally) as vehicle. Animals of Group II were treated with 3-NP for four successive days, at the dose of 20 mg/kg, intraperitoneally (i.p.). Animals that received Chrysin for the period of four consecutive days with the dose of 50 mg/kg, orally twice daily (30 min pre-treatment and 6 h post-treatment) following 3-NP administration served as Group III. After the treatment regime, animals were evaluated for neurobehavioral alterations and brain homogenates were used for estimation of neurotoxicity marker activity and neurotransmitter level along with histological assessment. The significant alteration in neurobehavioral, biochemical and neuronal structure in striatal part of brain was observed in the 3-NP administered (Group II) animals. It was observed that co-treatment of Chrysin with 3-NP treated rats the rotarod performance, grip strength, stride length as well as monoamine oxidase activity and serotonin levels were elevated. The results of this study reveal that Chrysin treatment alleviated the neurobehavioral, biochemical and histological alterations against HD symptoms in rats. [ABSTRACT FROM AUTHOR]

A bench scale system consisting of an up-flow packed bed bioreactor (UAPBR) made of polyurethane foam was used for the treatment and regeneration of aqueous solution of ferrous-NTA scrubbed with nitric oxide (NO). The biomass in the UAPBR was sequentially acclimatized under denitrifying and iron reducing conditions using ethanol as electron donor, after which nitric oxide (NO) gas was loaded continuously to the system by absorption. The system was investigated for different parameters viz. pH, removal efficiency of nitric oxide, biological reduction efficiency of FeNTA-NO and COD utilization. The FeNTA-NO reduction efficiency reached 87.8 % at a loading rate of 0.24 mmol L h, while the scrubber efficiency reached more than 75 % with 250 ppm NO. Stover-Kincannon and a Plug-flow kinetic model based on Michaelis-Menten equation were used to describe the UAPBR performance with respect to FeNTA-NO and COD removal. The Stover-Kincannon model was found capable of describing the FeNTA-NO reduction ( R = 8.92 mM h and K = 11.46 mM h) while plug-flow model provided better fit to the COD utilization ( U = 66.62 mg L h, K = 7.28 mg L). Analyses for pH, FeNTA, ammonium, nitrite concentration, and FTIR analysis of the medium samples indicated degradation of NTA, which leads to ammonium and nitrite accumulation in the medium, and affect the regeneration process. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke leads to mitochondrial alterations which are key factors for initiation of various cascades resulting in neuronal damage. Dopamine D2 receptor (D2R) agonist, Sumanirole (SUM) has been reported to possess anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the role of SUM in ischemic stroke (IS) has not been studied yet. The aim of the present study was to investigate the neuroprotective efficiency of SUM against ischemic injury and its possible effect on mitochondrial restorative mechanisms. Transient middle cerebral artery occlusion (tMCAO) was performed in Wistar rats for 90 min occlusion and 22.5 h reperfusion to mimic ischemic stroke. Post- treatment with Sumanirole (0.1 mg/kg and 1 mg/kg; s.c.) was done at 1 h, 6 h, 12 hand 18 h after surgery. In addition, neurobehavioral analysis, mitochondrial reactive oxygen species and mitochondrial membrane potential by flow cytometric analysis, mitochondrial complexes analysis, infarct size evaluation and histological analysis were performed. Sumanirole restored behavioural alterations as measured by rotarod performance, grip strength, adhesive tape removal analysis and neurological deficits. In addition, it also refurbished mitochondrial dysfunction by decreasing mitochondrial reactive oxygen species production, elevating mitochondrial membrane potential and by protecting the activity of mitochondrial complexes along with histological alterations. As a result, infarct sizes were markedly reduced in tMCAO surgery animals. Findings from the study provide evidence that SUM promotes neuronal survival in in vivo model of IS through mitochondria mediated neuroprotective features. • We investigated the neuroprotective efficiency of highly selective dopamine D2 agonist Sumanirole against ischemic injury. • Sumanirole restored behavioural alterations and neurological deficits in a stroke rodent mode. • Mitochondrial dysfunction was attemnuated by decreasing mitochondrial ROS production. • Infarct sizes were markedly reduced in tMCAO surgery animals. • Our study provides evidence for mitochondrial mediated neuroprotective features of Sumanirole against ischemic stroke. [ABSTRACT FROM AUTHOR]

Melatonin is a neurohormone that is linked to the pathogenesis of schizophrenia. The aim of this study was to assess the potential of melatonin in attenuating MK-801 induced schizophrenia-like behavioral and brain neurotoxicity markers. Swiss albino mice were assigned into three groups (n = 6). Animals were administered MK-801 (1 mg/kg/mL, i. p.). MK-801 treated animals were supplemented with melatonin (10 mg/kg/1 mL i. p.) 10 min prior to MK-801 injection. The relative degrees of modulation of induced behaviors by melatonin were assessed in the open field, elevated plus maze, grip strength and rota rod. The changes in neurotoxicity enzymes and neuronal activity (c-fos) were demonstrated in this study. MK-801 injection effected normal open-field behaviors, c-fos expression, motor coordination and muscular strength. Melatonin was able to reduce the histological changes in the prefrontal cortex of mice brain. Our data demonstrated that the treatment with melatonin attenuates the schizophrenic like symptoms in the mice having a protective effect on prefrontal cortex region of brain by mitigating the alteration of neurotoxicity markers. The protective effect of the treatment was shown to reduced elevation of AChE, c -fos expression and histopathological alterations. [ABSTRACT FROM AUTHOR]

Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage. Therefore, the purpose of this study was to determine whether one such agent, melatonin (Mel), could confer protection against Oxa-induced neurotoxicity in SH-SY5Y cells. Results from the present study found Oxa to significantly reduce SH-SY5Y cell viability in a dose-dependent manner. Alternatively, we found Mel pre-treatment to SH-SY5Y cells to attenuate Oxa-induced toxicity, resulting in a markedly increased cell viability. Mel exerted its protective effects by regulating reactive oxygen species (ROS) production and reducing superoxide radicals inside Oxa-exposed. In addition, we observed pre-treatment with Mel to rescue Oxa-treated cells by protecting mitochondria. As Oxa-treatment alone decreases mitochondrial membrane potential (Δψm), resulting in an altered Bcl-2/Bax ratio and release of sequestered cytochrome c, so Mel was shown to inhibit these pathways. Mel was also found to inhibit proteolytic activation of caspase 3, inactivation of Poly (ADP Ribose) polymerase, and DNA damage, thereby allowing SH-SY5Y cells to resist apoptotic cell death. Collectively, our results suggest a role for melatonin in reducing Oxa induced neurotoxicity. Further studies exploring melatonin’s protective effects may prove successful in eliciting pathways to further alter the neurotoxic pathways of platinum compounds in cancer treatment. [ABSTRACT FROM AUTHOR]

Bicyclic azetidine compounds possess antimalarial activity via targeting of the cytoplasmic Plasmodium falciparum (Pf) protein translation enzyme phenylalanine-tRNA synthetase (cFRS). These drugs kill parasites both in vitro and in vivo , including the blood, liver, and transmission developmental stages. Here we present the co-crystal structure of Pf cFRS with a potent inhibitor, the bicyclic azetidine BRD7929. Our studies reveal high-affinity binding of BRD7929 with Pf cFRS along with exquisite specificity compared with the human enzyme, leading in turn to potent and selective inhibition of the parasite enzyme. Our co-crystal structure shows that BRD7929 binds in the active site in the α subunit of Pf cFRS, where it occupies the amino acid site, an auxiliary site, and partially the ATP site. This structural snapshot of inhibitor-bound Pf cFRS thus provides a platform for the structure-guided optimization of novel antimalarial compounds. [Display omitted] • BRD7929 is a highly potent inhibitor of Pf cFRS • The co-crystal structure reveals the binding mode of BRD7929 to Pf cFRS • A mutant human-like Pf cFRS protein provides insights into drug selectivity Sharma et al. reveal the structural basis for the inhibition of cytoplasmic Plasmodium falciparum phenylalanine tRNA synthase (Pf cFRS) by the potent and highly selective antimalarial compound BRD7929. Overall, this work provides insights for ongoing structure-based drug design efforts based on the bicyclic azetidine series. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cubosomes have a higher surface area and volume due to its unique geometry. • Chitosan and Hyaluronic acid inhibits opsonization and RES clearance. • Hyaluronic acid modified cubosomes utilized to actively target CD44 receptors. • They suppress tumour nodules, activate caspases, upregulate BAX and downregulate Bcl-2. • Serum metabolomics revealed restoration of metabolites to normal levels. This study aimed at the development of hyaluronic acid-functionalised imatinib mesylate cubosomes (HA-IM-CBs) that might be useful in CD44 targeting against hepatic cancer. The HA-IM-CBs had a 130.7 ± 2.92 nm particle size, −31.40 ± 2.76 mV zeta potential, and 76.14 ± 2.69% release. The architecture of HA-IM-CBs was confirmed using HR-TEM and AFM. When compared to plain IM and IM-CBs, in vitro experiments revealed that HA-IM-CBs outperformed by significantly reducing cell viability. DAPI staining and ROS corroborated the apoptotic effects. Biodistribution and Pharmacokinetics studies showed that HA-IM-CBs exhibit a higher drug concentration in tumour tissue and better pharmacokinetic activity. This is the first study to show that HA-IM-CBs had CD44 targeting activity against HCC. CD44 regulates apoptosis via Bcl-2 family proteins and caspases, which interact with HA. Higher levels of e-NOS, BAD, BAX, and Cyt C and lower expressions of Bcl-xl, i-NOS, and Bcl-2 demonstrated the anti-HCC potential of HA-IM-CBs in qrt-PCR investigations. The remarkable therapeutic potential of HA-IM-CBs began with substantial stimulation of CD44 regulated caspase-mediated mitochondrial apoptotic pathway, accountable for their anti-HCC activity. The perturbed metabolites are restored to acceptable levels as indicated by metabolomic studies (1H NMR). Interestingly, the antineoplastic effect of HA-IM-CBs was proven to be potentially valuable against HCC. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is a rapidly increasing global burden and is associated with severe neurological decline and mortality. There is urgent requirement of the efforts, aimed to identify therapeutic strategies that are effective in clinic to promote significant recovery from IS. Studies have shown that mitochondria mediated neuroprotection can be a competent target against ischemic damage. Therefore, we examined whether mitochondrial impairment is regulated by Piperine (PIP), an alkaloid of Piper Longum , which has neuroprotective activity against ischemic brain injury. In this study, transient middle cerebral artery occlusion (tMCAO) surgery was performed on male Wistar rats for 90 min followed by 22.5 h of reperfusion for mimicking the IS condition. This study consisted of three groups: sham, tMCAO and tMCAO + PIP (10 mg/kg b.wt., p.o/day for 15 days), and studied for behavioral tests, infarct volume, brain pathological changes, mitochondrial dysfunction, inflammation alongwith cell survival status. PIP pre-treatment showed reduction in neurological alterations and infarct volume. In addition, PIP pre-treatment suppressed the mitochondrial dysfunction and might have anti-apoptotic potential by preventing Cytochrome c (Cyt c) release from mitochondria to cytoplasm and caspase 3 activation. It also regulates pro-apoptotic, Bax and anti-apoptotic, Bcl-2 proteins accompanied by glial fibrillary acidic protein (GFAP) positive cells in cortex region. Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR) results also showed that PIP reduced the expression of pro-inflammatory protein, interleukin-1 β (IL-1β) and enhanced cell survival by restoring the activity of brain derived neurotrophic factor (BDNF) and its transcription protein, cAMP response element binding protein (CREB). Taken together, PIP reduced the mitochondrial dysfunction, neurological impairment, and enhanced neuronal survival. In conclusion, our findings reinforce PIP as an effective neuroprotective agent and provide important evidence about its role as a potential target to serve as a promising therapy for treatment of IS. Schematic representation of mitochondria mediated mechanisms of neuroprotection against ischemic stroke provided by Piperine. Piperine can inhibit mitochondrial dysfunction by suppressing inflammation and mitochondrial ROS mediated alterations in ETC and reduced mitochondrial membrane permeability (Δѱm) thereby preserving mitochondrial Cyt c level through blockage of mitochondrial permeability transition pore (mPTP). Finally, it might increase anti-apoptotic (Bcl-2) protein and decrease pro-apoptotic (Bax) protein, and alleviated neuronal cell death. Piperine also involved in cell survival processes and ultimately rescued neuronal morphological alterations and neurobehavioral abnormalities. IL-1β (Interleukin-1β), GFAP (Glial Fibrillary Acidic Protein), LPO (Lipid Peroxidation), GSH (Glutathione), Cyt c (Cytochrome c), Electron transport chain (ETC), Reactive oxygen species (ROS). [Display omitted] • Ischemic animals pre-treated with piperine showed reduced neurological alterations and infarct volume. • Piperine improved mitochondrial dysfunction. • Piperine showed anti-apoptotic potential by preventing cytochrome c release from mitochondria to cytoplasm. • PIP reduced neurological impairment and enhanced cell survival. [ABSTRACT FROM AUTHOR]

• Our study provides critical link between mitochondria dysfunction and Alzheimers Disease. • Melatonin has potential to restore the normal mitochondria function in Aβ mediated neurodegeneration in AD. • Melatonin inhibits the excessive production of ROS and improves mitochondrial membrane potential. • Melatonin normalizes the expression of p-JNK and caspase 3 in AD. Alzheimers's disease is one of the alarming neurodegenerative disease and it is of global concern.The hallmarks of the disease are the amyloid beta (Aβ) aggregation and presence of neurofibrillary tangles (NFTs). The interaction of Aβ with macromolecular targets affects the normal cellular functions. The amyloid peptide interaction with cellular surfaces may trigger the intracellular cascades of signalling. Interaction of Aβ with mitochondria leads to the generation of free radicals. Many studies have suggested the involvement of mitochondrial dysfunction in Alzheimer's disease. Melatonin prevents mitochondria stress and by means of activating the antioxidant systems it protects the death of neurons. Although the study have been already conducted on Aβ42 infused or injury induced animal models but till date there is no reports of such studies on transgenic model of Drosophila melanogaster. In the present study, we have taken UAS/Gal4 system for the development of transgenic flies that overexpress Aβ42 in the brain of Drosophila. With the help of these transgenic flies we have analyse different experiments like behavioural parameters, oxidative stress parameters and protein expression through western blotting in the presence of melatonin. We have found that melatonin significantly ameliorated the toxicity caused by the Aβ42 overexpression. Thus the present study could be beneficial to find out the role of melatonin in transgenic flies overexpressing human Aβ42. [ABSTRACT FROM AUTHOR]