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3,4-dihydroxyphenethylamine (dopamine) depletion, inhibition of complex I activity, oxidative stress, and glutamate excitotoxicity are cardinal biochemical features of neurotoxicity induced by systemic unilateral infusion of rotenone. Kolaviron (KV), a biflavonoid from Garcinia kola seeds, has been proven to have pharmacological effects against neurotoxicity. Coenzyme Q10 plays an essential role in mitochondrial oxidative phosphorylation and as an antioxidant. This study examined the comparative influence of kolaviron and coenzyme Q10 on complex I activity, dopamine metabolism, glutamate clearance, and redox stress in rotenone-induced neurotoxicity in the cortex, hippocampus, and striatum of the brain of rats. Adult Male Wistar rats were pretreated with 200 mg/kg KV or 100 mg/kg coenzyme Q10 for 7 days followed by administration of a progressive six doses of 1.5 mg/kg rotenone within the next 48 h after which the animals were euthanized and the brain excised. On the cortical, hippocampal, and striatal regions of the brain, complex I activity, dopamine metabolism, oxidative stress markers, as well as glutamate metabolism were carried out and analyzed. In all brain regions examined, KV and coenzyme Q10 pretreatment modulated complex I activity, ameliorated redox imbalance, and enhanced dopamine metabolism via increasing the activity of tyrosine hydroxylase and decreasing monoamine oxidase activity. KV facilitated glutamate clearance through augmentation of glutamate dehydrogenase and glutamine synthetase activities. The activity of KV was comparable to that of the mitochondrial membrane antioxidant compound, coenzyme Q10, this indicates that KV is a promising therapeutic agent in the treatment of Parkinson’s disease and its activity compares well with coenzyme Q10

The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g−1 feed) and ciprofloxacin (0.5 and 0.25 μg g−1 feed) for 63 days. Results demonstrated that the reductions in the body rotation, maximum speed, turn angle, path efficiency, distance traveled, episodes, and time of mobility induced by atrazine or ciprofloxacin per se was exacerbated in the co-exposure group. The altered exploratory and locomotor in insects singly and jointly exposed to ciprofloxacin and atrazine were verified by track plots and heat maps. Furthermore, we observed a decrease in acetylcholinesterase and anti-oxidative enzyme activities with concomitant elevation in the levels of lipid peroxidation, nitric oxide, and reactive oxygen and nitrogen species were significantly intensified in the midgut, hemolymph, and head of insects co-exposed to ciprofloxacin and atrazine. In conclusion, exposure to binary mixtures of ciprofloxacin and atrazine elicited greater locomotor and exploratory deficits than upon exposure to the individual compound by inhibiting acetylcholinesterase activity and induction of oxido-inflammatory stress responses in the insects. N. cinerea may be a usable model insect for checking contaminants of ecological risks.

Chasmanthera dependens stem is used in African traditional medicine as a remedy for various maladies; however, scientific evidence to validate its uses in gastric ulcer healing is lacking. This stu...

Phytochemicals derived from plant sources are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress-related ailments. Dichloromethane/methanol (1...

Reproductive toxicity associated with excessive exposure to multi-walled carbon nanotubes (MWCNTs), which are commonly used in medicine as valuable drug delivery systems, is well documented. Kolaviron, a bioflavonoid isolated from Garcinia kola seeds, elicits numerous health beneficial effects related to its anti-inflammatory, anti-genotoxic activities, anti-apoptotic, and antioxidant properties. However, information on the role of kolaviron in MWCNTs-induced reproductive toxicity is not available in the literature. Herein, we assessed the protective effects of kolaviron on MWCNTs-induced dysfunctional reproductive axis in rats following exposure to MWCNTs (1 mg/kg) and concurrent treatment with kolaviron (50 or 100 mg/kg body weight) for 15 successive days. Results showed that MWCNTs-induced dysfunctional reproductive axis as evidenced by deficits in pituitary and testicular hormones, marker enzymes of testicular function, and sperm functional characteristics were abrogated in rats co-administered with kolaviron. Moreover, co-administration of kolaviron-abated MWCNTs-induced inhibition of antioxidant enzyme activities increases in oxidative stress and inflammatory indices. This is evidenced by diminished levels of tumor necrosis factor-alpha, nitric oxide, lipid peroxidation, reactive oxygen, and nitrogen species as well as reduced activity of myeloperoxidase in testes, epididymis, and hypothalamus of the rats. Biochemical data on the chemoprotection of MWCNTs-induced reproductive toxicity were corroborated by histological findings. Taken together, kolaviron suppressed dysfunctional reproductive axis associated with MWCNTs exposure via abrogation of oxidative stress and inflammation in male rats.

The asymptomatic and clinical stages of Parkinson's disease (PD) are associated with comorbid non-motor symptoms including gastrointestinal (GI) dysfunction. Although the neuroprotective and gastroprotective roles of kolaviron (KV) have been reported independently, whether KV-mediated GI-protective capacity could be beneficial in PD is unknown. We therefore investigated the modulatory effects of KV on the loss of dopaminergic neurons, locomotor abnormalities, and ileal oxidative damage when rats are lesioned in the nigrostriatal pathway. KV treatment markedly suppressed the behavioral deficit and apomorphine-induced rotations associated with rotenone lesioning. KV attenuated the loss of nigrostriatal dopaminergic neurons and perturbations in the striatal glucose-regulated protein (GRP78) and X-box binding protein 1 (XBP1) levels. Ileal epithelial injury following stereotaxic rotenone infusion was associated with oxidative stress and marked inhibition of acetylcholine esterase activity and reduced expression of occludin in the crypt and villi. While KV treatment attenuated the redox imbalance in the gut and enhanced occludin immunoreactivity, acetylcholinesterase activity was not affected. Our data demonstrate ileal oxidative damage as a characteristic non-motor gut dysfunction in PD while showing the potential dual efficacy of KV in the attenuation of both neural defects and gut abnormalities associated with PD.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Currently, the precise pathogenic detail of PD is not entirely clear and first line therapeutics fail to attenuate the progress of the disease. In this study, we examined the neuroprotective effect of kolaviron, a natural antioxidant and anti-inflammatory biflavonoid from Garcinia kola seed, on behavioural impairment, neurodegeneration, oxidative stress and neuroinflammation in an acute MPTP-induced PD model. Kolaviron mitigated the frequently interrupted MPTP-associated hyperkinesia, inefficient gait, immobility, inability to pay attention to sizable holes on walking path, habitual clockwise rotations characterized with minimal diversion of movements and impaired balance. Also, kolaviron suppressed MPTP-mediated striatal oxidative stress, depletion as well as degeneration of dopaminergic terminals, reduced DJ-1 secretion and upregulated expression of caspase-3. Kolaviron facilitated cytoprotective antioxidant response and prevented MPTP-mediated neuroinflammation by blocking striatal infiltration of peripheral CD45R positive cells. Additionally, kolaviron reversed MPTP-induced inhibition of acetylcholinesterase activity. Together, our study provides evidence that the neuroprotective capacity of kolaviron to modulate striatal degeneration, behavioural impairment, antioxidant/redox imbalance and neuroinflammation implicated in the pathogenesis of PD may involve upregulation of DJ-1 secretion and inhibition of CD45R cells infiltration. Our data recommend kolaviron as a possible neuroprotective strategy in the management of Parkinson’s disease and the associated behavioural complications, albeit the identity of MPTP-associated striatal CD45R infiltrate needs to be further characterized.

The antiplasmodial effect of methanol extract of Paullinia pinnata leaves was investigated in mice to observe the outcome on oxidative stress and inflammation in the liver. Wistar mice of both sexe...

Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.

This present study was designed to investigate ameliorating potential of thymol (THY) on hexachlorobenzene (HBC)-induced epididymal and testicular toxicities in adult male rats. Forty adult male rats were orally treated by gavage daily for 28 consecutive days and divided into four groups; control group administered with corn oil, HBC-treated group (16 mg/kg b. wt), thymol-treated group (30 mg/kg b. wt), and HBC + THY-treated group. The results revealed that HBC exposure caused a significant decrease in the body weight change, organ weights, sperm functional parameters, serum testosterone level with widespread histological abnormalities. Furthermore, HBC-treated rats showed increased in the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), epididymal and testicular myeloperoxidase activity, tumor necrosis-α, interleukin-1β level and caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA), reactive oxygen species (RONS) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-treatment of THY with HBC alleviated the HBC-induced epididymal and testicular toxicities. Our findings revealed that HBC acts as a reproductive toxicant in rats and thymol could be a potential remedial agent for HBC-induced reproductive toxicity.

The present study investigated the individual and collective effect of organochlorinated fungicide hexachlorobenzene (HCB) and manganese (Mn), a metal, on the hepatorenal function in adult rats. Rats were divided into four groups of rats comprising of control, HCB alone (15 mg/kg), Mn alone (10 mg/kg) and co-exposure group that were orally treated for 25 consecutive days. After sacrifice, hepatorenal damage and antioxidant status markers, myeloperoxidase (MPO) activity, levels of nitric oxide, total antioxidant capacity (TAC), total oxidative stress (TOS) and lipid peroxidation (LPO) were analyzed spectrophotometrically. Levels of tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β) and caspase-3 activity were assessed using ELISA. Results revealed that the HCB administration significantly (

Atrazine (ATZ) exposure is associated with reproductive dysfunction in both animals and humans. Myricetin, a flavonoid compound, is well documented for its numerous pharmacological activities. However, the impact of myricetin on the atrazine-mediated dysfunctional hypothalamic-pituitary-testicular axis is not known. This study investigated the role of myricetin on the atrazine-induced alterations in the male reproductive axis in rats orally gavaged with ATZ alone (50 mg/kg) or co-treated with ATZ + myricetin (MYR) at 5, 10, and 20 mg/kg for 30 consecutive days. Myricetin assuaged ATZ-induced reductions in intra-testicular testosterone, serum follicle-stimulating hormone, luteinizing hormone, and testosterone, coupled with decreases in alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activities. Also, MYR treatment improved epididymal sperm count and motility and decreased sperm defects in ATZ-treated rats. Testicular sperm number, daily sperm production, and sperm viability remained unchanged in all treatment groups. Administration of MYR abated ATZ-mediated depletion in antioxidant status, an increase in myeloperoxidase activity, nitric oxide, hydrogen peroxide, malondialdehyde levels, and reactive oxygen and nitrogen species, as well as the histological lesions in the hypothalamus, epididymis, and testes of treated animals. All in all, MYR mitigated atrazine-mediated functional changes in the reproductive axis via anti-inflammatory and antioxidant mechanisms in atrazine-exposed rats. Dietary intake of MYR could be a worthy chemoprotective approach against reproductive dysfunction related to ATZ exposure.

Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochemical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p

Sodium fluoride (NaF) is used in water fluoridation and dental products such as mouth rinses and toothpastes. Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory properties. The present study was carried out to evaluate the toxicity of NaF and the protective role of resveratrol in Drosophila melanogaster. For longevity assay, Harwich strain of D. melanogaster was treated with NaF (0, 10, 30, 50, 70 and 90 mg/kg diet) throughout the lifespan and daily mortality recorded. Then, flies were again treated with similar doses of NaF for seven days to evaluate survival rate and oxidative stress markers. Thereafter, 60 mg resveratrol/kg diet was selected to determine its ameliorative role in NaF (70 mg/kg)-induced toxicity in flies: Group A (control), Group B (60 mg resveratrol/kg diet), Group C (70 mg NaF/kg diet), and Group D (resveratrol, 60 mg/kg diet) + NaF, 70 mg/kg diet). Thereafter, Glutathione-S-transferase (GST), catalase and acetylcholinesterase (AchE) activities, as well as total thiol (T-SH), nitrites/nitrates and hydrogen peroxide (H2O2) levels were determined. The results showed that resveratrol prevented NaF-induced elevation of H2O2and nitrites/nitrates levels, as well as catalase activity. In addition, resveratrol restored NaF-induced inhibition of GST and AChE activities and depletion of T-SH content ( P Impact statementD. melanogaster was used to understand the impact of NaF on lifespan and emergence rate as well as the rescue role of resveratrol. These parameters are difficult to carry out in previously used models such as rodents. This further enforces in part, the suitability of D. melanogaster in studying NaF-induced toxicity and the therapeutic effects of drugs. Additionally, we found that resveratrol rescued D. melanogaster from oxidative stress-induced by sodium fluoride (NaF) administration. This study is of public health significance as it indicated that the consumption of fruits rich in resveratrol such as grapes may offer protective role against inadvertent exposure to NaF and related chemicals.

Manganese (Mn) is an essential nutrient element. However, Mn is causing great environmental and occupational exposure health risk concern globally, even high rate of alcohol consumption. There is dearth of scientific information on the interaction of manganese (Mn) and ethanol (EtOH) on hippocampal functions. This study was designed to investigate the effect of EtOH on Mn – induced hippocampal toxicity with special reference to spatial learning and memory and its underlying mechanism in adults male Wistar Rats. Rats were exposed to Mn alone at 30 mg/kg or co-expose with EtOH at 1.25 and 5 g/kg body weight by oral gavage for 35 consecutive days. Morris Water Maze task was used to assessed spatial learning and memory. Subsequently, oxidative/nitrosative stress, neuro-inflammation (myeloperoxidase and cyclooxygenase-2) and protein expression of apoptotic proteins (p53 and Bax), active executioner caspase (caspase-3) and B – cell lymphoma – 2 (Bcl – 2) markers in the hippocampus were investigated. The results indicate that Mn and EtOH exposure induces spatial learning and memory deficits, increase oxidative/nitrosative stress, neuro-inflammation resulting in enhanced hippocampal apoptosis. Moreover, the results indicated that Mn co-exposure with EtOH at 1.25 and 5 g/kg body weight further exacerbates neurotoxicity in rat hippocampus when compared with single dose of Mn and EtOH alone. Collectively, EtOH increases Mn – induced oxidative/nitrosative stress, neuro-inflammation and hippocampal apoptosis via mechanism involving oxidative damages of cellular constituents, neuronal inflammation and subsequent upregulation of Bax and caspase-3 and downregulation of Bcl-2 protein expression via p53 dependent/independent pathways to induced hippocampal apoptosis associated with impaired spatial learning and memory.

Clinical and experimental data have demonstrated that diabetes is associated with neurological complications. Protocatechuic acid (PCA) is a phenolic phytochemical widely reported to possess antidiabetic property. However, there is no scientific information on the influence of PCA on diabetes-induced neurotoxicity. The present study aimed at investigating the neuroprotective mechanism of PCA in streptozotozin (STZ)-induced type 1 diabetic rats orally treated with PCA (50 mg/kg body weight) or glibenclamide (5 mg/kg body weight) for 45 consecutive days. Locomotor behavior was analyzed using video-tracking software during the 8-min trial in a novel environment whereas the pancreas, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results showed that treatment of diabetic rats with PCA at 50 mg/kg significantly (p 0.05) improved the locomotor and motor activities including the average speed, total time mobile, distance travelled, body rotation, turn angle, forelimb grip and grooming when compared with untreated diabetic rats. Moreover, the prevention of diabetes-mediated increase in acetylcholinesterase activity, biomarkers of inflammatory and oxidative stress as well as caspase 3 activity by PCA treatment was accompanied by improved pancreatic, cerebral and cerebellar architectures. Collectively, the neuroprotective mechanisms of PCA is related to its antioxidant, anti-inflammatory and anti-apoptotic activities.

This study investigated the effects of post-treatment with kolaviron on a 2-Vessel Occlusion (2-VO) model of cerebral ischemia/reperfusion (I/R) injury in rats to ascertain its level of efficacy as a potential therapeutic agent for stroke. Male Wistar rats submitted to 30 min of bilateral common carotid artery occlusion and 24 h of reperfusion were treated with kolaviron (25–100 mg/kg) or 20 mg/kg quercetin immediately after reperfusion and 2 h post reperfusion. At the end of the period of reperfusion, animals were scored for motor and cognitive deficits. Brain relative weight and water content were determined. Cortices, striata and hippocampi were dissected and processed for estimation of markers of oxidative stress, inflammation, neurotransmitter dysregulation and excitotoxicity. In addition, assessment of hippocampal mitochondrial integrity and histopathological examination of the cortical, striatal and hippocampal regions were carried out. There was reversal of 2-VO ischemia/reperfusion (I/R) induced motor and cognitive deficits by kolaviron post-treatment. Post-treatment with kolaviron also attenuated I/R-induced oxidative stress, neuroinflammatory events, excitotoxicity as well as mitochondrial dysfunction in brain tissues. Histopathological findings showed amelioration of I/R-induced neuronal cell damage by kolaviron post-treatment. The results revealed the multi-target neurotherapeutic activity of kolaviron and suggest that it is a promising candidate for drug development against stroke.

Acid-sensing ion channels (ASICs) play significant roles in numerous neurological and pathological conditions, including pain. Although acid-induced nociception has been characterized previously in zebrafish, the contribution of ASICs in modulating pain-like behaviors is still unknown. Here, we investigated the role of amiloride , a nonselective ASICs blocker, in the negative modulation of specific behavioral responses in a zebrafish-based model of acute visceral pain. We verified that intraperitoneal injection (i.p.) of 0.25, 0.5, 1.0, and 2.0 mg/mL amiloride alone or vehicle did not change zebrafish behavior compared to saline-treated fish. Administration of 2.5% acetic acid (i.p.) elicited writhing-like response evidenced by the abnormal body curvature and impaired locomotion and motor activity. Attenuation of acetic acid-induced pain was verified at lower amiloride doses (0.25 and 0.5 mg/mL) whereas 1.0 and 2.0 mg/mL abolished pain-like responses. The protective effect of the highest amiloride dose tested was evident in preventing writhing-like responses and impaired locomotion and vertical activity. Collectively, amiloride antagonized abdominal writhing-like phenotype and aberrant behaviors, supporting the involvement of ASICs in a zebrafish-based model of acute visceral pain.

This study examined the protective effect of 6-Gingerol (6G) against lipopolysaccharide (LPS)-induced cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation. Male rats were allocated into six groups in this manner; Group I placed on normal saline only. Group II was treated for 7 days with LPS alone intraperitoneally at 250 µg/kg body weight (bw). Group III received 6G alone at 50 mg/kg bw orally for 14 days. Groups IV and V received 6G at 20 and 50 mg/kg bw for 7 days, respectively, and LPS for another 7 days to induce neurotoxicity. Group VI received 5 mg/kg bw of donepezil for 7 days and LPS for 7 days. Pretreatment with 20 and 50 mg/kg bw of 6G protected against LPS-mediated learning and memory function, and also locomotor and motor deficits. Besides, 20 and 50 mg/kg bw 6G mitigated LPS-induced alteration in markers of oxidative stress. Furthermore, induction of amyloidogenesis associated with disruption of histoarchitecture and high expression of interleukin 1β, inducible nitric oxide synthase, amyloid precursor protein (APP), β-secretase 1, and brain-derived neurotrophic factor by LPS was mitigated by the two doses of 6G in the rat hippocampus and cerebral cortex region of the brain. 6G pretreatment at the two doses mitigated LPS-mediated histopathological changes in the hippocampus and cerebral cortex of rats. Overall, our results demonstrate that the protective effect of 6G is mediated through the reversal of neurobehavioral deficit, oxidative stress, inflammation, and amyloidogenesis, thus making 6G a possible chemoprophylactic agent against brain injury as a result of LPS exposure. PRACTICAL APPLICATIONS: In the search for a holistic prevention of inflammation-associated neurodegeneration, nutraceuticals are becoming prominent. Hence, this study presents 6G, an active constituent of ginger, as a chemoprotective, antioxidant, and anti-inflammatory agent, which is able to ameliorate cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation in LPS-induced rat model of neuroinflammation.

The present study examined the influence of selenium on ciprofloxacin-mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co-treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacin-treated in rats. Selenium treatment also mitigated ciprofloxacin-mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1 ) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1 -induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated significant (p < .05) abatement of AFB1 -induced anxiogenic-like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1 -induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1 -mediated decrease in interleukin-10 and elevation of inflammatory indices, namely tumor necrosis factor-α, myeloperoxidase activity, interleukin-1β, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1 -induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.

Manganese (Mn) exposure is causing public health concerns as well as heavy alcohol consumption. This study investigates the mechanisms of neurotoxicity associated with Mn and ethanol (EtOH) exposure in the rat cerebellar cortex. Experimental animals received 30 mg/kg of Mn alone, 5 g/kg of EtOH alone, co-exposed with 30 mg/kg of Mn and 1.25 or 5 g/kg EtOH, while control animals received water by oral gavage for 35 days. Subsequently, alterations in the neuronal morphology of the cerebellar cortex, oxidative/nitrosative stress, acetylcholinesterase (AChE) activity, neuro-inflammation and protein expression of p53, BAX, caspase-3, and BCL-2 were investigated. The results indicate that Mn alone and EtOH alone induce neuronal alterations in the cerebellar cortex, decrease glutathione level and antioxidant enzyme activities, along with an increase in AChE activity, lipid peroxidation, and hydrogen peroxide generation. Mn alone and EtOH alone also increased neuro-inflammatory markers, namely nitric oxide, myeloperoxidase activity, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB (NF-κB) levels in the cerebellar cortex. Immunohistochemistry analysis further revealed that exposure of Mn alone and EtOH alone increases the protein expression of cyclooxygenase-2, BAX, p53, and caspase-3 and decrease BCL-2 in the rat cerebellar cortex. Furthermore, the results indicated that Mn co-exposure with EtOH at 1.25 and 5 g/kg EtOH significantly (p ≤ .05) increases the toxicity in the cerebellum when compared with the toxicity of Mn or EtOH alone. Taken together, co-exposure of Mn and EtOH exacerbates neuronal alterations, oxidative/nitrosative stress, AChE activity, pro-inflammatory cytokines, NF-κB signal transcription, and apoptosis induction in the rat cerebellar cortex.

The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g

Pterocarpus mildbraedii (PME) is a green leafy vegetable from the Papilionaceae family. This study evaluated the anti-inflammatory activity of PME in Wistar rats exposed to experimental hepatotoxicity using propanil (PRP), a post-emergent herbicide. Animals were grouped as control, PRP, PME, and PME + PRP. After 7 days, the levels of stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), p38 mitogen-activated protein kinase (p38 MAPK), and signal transducer and activator of transcription (STAT-3) were measured in rat liver. Furthermore, myeloperoxidase (MPO) and nitric oxide (NO) levels, as well as protein expressions of nuclear factor-κB (NF-κB p65), inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) were determined. Compared with PRP-treated rats, PME significantly reduced the hepatic MPO and NO levels. PME also diminished NFκB, iNOS, and COX-2 protein expressions in PRP-treated rats. This study showed that Pterocarpus mildbraedii leaves produce active principles with relevant anti-inflammatory potential. PRACTICAL APPLICATIONS: Previous studies have shown that bioactive principles contained in medicinal plants can offer protection against chemically induced inflammation. Pterocarpus mildbraedii leaves, with rich content of polyphenols, flavonoids, and essential fatty acids, could be exploited as a therapeutic agent against pesticide-induced oxidative stress and inflammation. This current study has also shown that the potential of PME as a functional food is boosted by the presence of α-linolenic acid, an omega-3-fatty acid known to possess anti-inflammatory activity. Here, we elucidated the cellular mechanisms of the anti-inflammatory action of PME.

The neurotoxic impact of dietary exposure to aflatoxin B

Aflatoxin B1 (AFB1) is reported to elicit adverse reproductive outcomes in animals. Gallic acid (GA) is known to exhibit antioxidant and inflammatory bioactivities. The impact of GA on AFB1-facilitated reproductive dysfunction is nonexistent in literature. This investigation elucidated GA protective effect on AFB1-induced reproductive toxicities in rats, exposed for 28 consecutive days to AFB1 (75 µg/kg), or co-treated with GA (20 or 40 mg/kg) body weight. AFB1 significantly (p < 0.05) reduced testicular function biomarkers, serum hormonal levels, and functional sperm characteristics in experimental animals. GA abated AFB1-induced increases (p < 0.05) in lipid peroxidation and reactive oxygen and nitrogen species, suppressed myeloperoxidase, interleukin-1β, nitric oxide, and tumor necrosis factor-α levels—inflammatory biomarkers—in testes, epididymis, and hypothalamus. Furthermore, GA improved antioxidant defenses and alleviated reduction in interleukin-10, caspase-3 activation, and histological variations in epididymis, testes, and hypothalamus of rats dosed with AFB1. Conclusively, GA enhanced reproductive function in AFB1-exposed rats by modulating inflammatory, oxidative stress, and apoptosis mediators.Impact statementInfertility resulting from reproductive deficiency can be stressful. Exposure to aflatoxin B1, a dietary mycotoxin prevalent in improperly stored grains, is reported to elicit reproductive insufficiencies and infertility. We, therefore, examined the likely beneficial effect of gallic acid (GA) a phytochemical, recognized to exhibit in vitro and in vivo pharmacological bioactivities against oxidative stress and related inflammatory damages in rats, since AFB1 toxicities are predicated on oxidative epoxide formation, in a bid to proffer new evidence to advance the field of nutriceutical application from plant-derived chemopreventive agents. Our findings will advance the field of chemoprevention by presenting data absent in the literature on GA. Our results demonstrate further evidence for GA conferred protection against AFB1-mediated histological lesions in testes, epididymis, and hypothalamus of treated rats; suppresses oxidative damages, relieved inflammatory and apoptotic responses, restored sperm functional characteristics, and hormonal levels relevant for reproductive integrity and function.

The adverse effect of Aflatoxin B1 (AFB1 ) exposure in both humans and rodents has been widely reported. The beneficial health effects of gallic acid (GA) against AFB1 -induced toxicity in vitro have been published. Here, we present in vivo findings on AFB1 and GA on hepatorenal function in rats, exposed to AFB1 (75 µg/kg body weight) only or co-treated with GA (20 or 40 mg/kg) for 28 successive days. AFB1 significantly increased pro-inflammatory biomarkers and suppressed IL-10 levels in rats' liver and kidney. AFB1 caused increased (p < .05) oxidative stress by decreasing antioxidant enzymes levels and increasing levels of reactive oxygen and nitrogen species. Furthermore, reduction (p < .05) in cellular glutathione (GSH) levels and increased (p < .05) hepatorenal markers of toxicity were detected in rats treated with AFB1 . These observed alterations were, however, reversed in GA co-treated rats. GA ameliorated AFB1 -induced hepatorenal dysfunction by decreasing oxidative stress and inflammation in rats. PRACTICAL APPLICATIONS: GA can chemoprotect against the damaging effects of toxins contaminating food. GA is widely distributed in plants and in use in industries as antioxidant, immune-regulator, and natural defense agent against infections when consumed. Here, we disclosed that GA ameliorates AFB1 -induced hepatorenal dysfunction by suppressing oxidative stress, inflammation, and enhanced apoptosis, thus improving hepatorenal functions in rats exposed to AFB1.

D-penicillamine (DPA) is an amino-thiol that has been established as a copper chelating agent for the treatment of Wilson’s disease. DPA reacts with metals to form complexes and/or chelates. Here, we investigated the survival rate extension capacity and modulatory role of DPA on Cu2+-induced toxicity in Drosophila melanogaster. Adult Wild type (Harwich strain) flies were exposed to Cu2+ (1 mM) and/or DPA (50 μM) in the diet for 7 days. Additionally, flies were exposed to acute Cu2+ (10 mM) for 24 h, followed by DPA (50 μM) treatment for 4 days. Thereafter, the antioxidant status [total thiol (T-SH) and glutathione (GSH) levels and glutathione S-transferase and catalase activities] as well as hydrogen peroxide (H2O2) level and acetylcholinesterase activity were evaluated. The results showed that DPA treatment prolongs the survival rate of D. melanogaster by protecting against Cu2+-induced lethality. Further, DPA restored Cu2+-induced depletion of T-SH level compared to the control (P

The reproductive toxicity associated with furan exposure in both animals and humans has been documented. Protocatechuic acid (PCA), a dietary polyphenolic chemical, reportedly elicits beneficial effects on the male reproductive system. However, the influence of PCA on the reproductive toxicity related to furan exposure is unavailable in the literature. The current study evaluated the effects of PCA on the dysfunctional reproductive axis caused by furan exposure in rats. Experimental animals were exposed to furan (8 mg/kg) or co-treated with furan (8 mg/kg) and PCA (25 or 50 mg/kg) for twenty-eight successive days. Results revealed that PCA treatment significantly alleviated furan-mediated declines in sperm production and characteristic qualities as well as in serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, and testosterone. Further, PCA attenuated furan-induced reduction in antioxidant enzyme activities and testicular function marker enzymes, namely lactate dehydrogenase, glucose-6-phosphate dehydrogenase, acid phosphatase, and alkaline phosphatase. PCA effectively mitigated furan-mediated increases in myeloperoxidase activity, levels of reactive oxygen and nitrogen species, nitric oxide, tumour necrosis factor-alpha, and interleukin-1β in testes, epididymis, and hypothalamus of rats. Moreover, PCA increased anti-inflammatory cytokine interleukin-10 but suppressed caspase-9 and caspase-3 activities and ameliorated injuries in the testes, epididymis, and hypothalamus of furan-treated rats. In conclusion, PCA ameliorated deficits in the hypothalamic-pituitary-gonadal axis function in furan-exposed rats by suppressing oxido-inflammatory stress and apoptosis.

Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to the ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate the impact of DCF on insects by assessing the behavior and antioxidant defense response in nymphs of N. cinerea exposed to DCF-contaminated food at 0, 0.5, 1.0 and 2.0 μg kg−1 feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in the head, midgut and hemolymph of the insects. Results indicated that DCF-exposed insects exhibited marked reduction in the maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas the total freezing time was increased compared with the control. The diminution in the exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in the head, midgut and hemolymph of the insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.

Background The ovotoxicity of 4-vinylcyclohexene diepoxide (VCD) has been established in several experimental models. Hesperidin (HSD) is a bi-flavonoid found in citrus fruits and has been reported to be a potent antioxidant and anti-inflammatory agent. Here, we have evaluated the rescue role of hesperidin on VCD-induced toxicity in the brain, ovary, and uterus of rats. Methods Six groups of rats containing ten rats in each group were orally given corn oil (control), hesperidin (100 mg/kg), hesperidin (200 mg/kg), VCD (250 mg/kg), VCD [(250 mg/kg)+hesperidin (100 mg/kg)] and VCD [(250 mg/kg)+hesperidin (200 mg/kg)] once a day for 30 days, respectively. Thereafter, we determined the selected biomarkers of oxidative damage, inflammation, endocrine balance, and histology of the reproductive organs. Results The data showed that hesperidin rescued VCD-induced increase in oxidative stress (hydrogen peroxide and malondialdehyde) and inflammatory (nitric oxide) biomarkers. In addition, hesperidin restored the reduction in antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase) activities and glutathione level in the brain, ovary, and uterus of rats (p Conclusions Overall, the rescue role of hesperidin on VCD-induced toxicity in the brain and reproductive organs of female rats may be due to its antioxidative and anti-inflammatory properties.

Exposure to pesticide chlorpyrifos (CPF) is associated with neurodevelopmental toxicity both in humans and animals. Diphenyl diselenide (DPDS) is a simple synthetic organoselenium well reported to possess antioxidant, anti-inflammatory and neuroprotective effects. However, there is paucity of information on the beneficial effects of DPDS on CPF-mediated brain injury and neurobehavioural deficits. The present study investigated the neuroprotective mechanism of DPDS in rats sub-chronically treated with CPF alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Endpoint analyses using video-tracking software in a novel environment revealed that co-treatment with DPDS significantly (p 0.05) protected against CPF-mediated locomotor and motor deficits precisely the decrease in maximum speed, total distance travelled, body rotation, absolute turn angle, forelimb grip strength as well as the increase in negative geotaxis and incidence of fecal pellets. The enhancement in the neurobehavioral activities of rats co-treated with DPDS was verified by track plot analyses. Besides, DPDS assuaged CPF-induced decrease in acetylcholinesterase and antioxidant enzymes activities and the increase in myeloperoxidase activity and lipid peroxidation level in the mid-brain, cerebral cortex and cerebellum of the rats. Histologically, DPDS co-treatment abrogated CPF-mediated neuronal degeneration in the cerebral cortex, dentate gyrus and cornu ammonis3 in the treated rats. In conclusion, the neuroprotective mechanisms of DPDS is related to the prevention of oxidative stress, enhancement of redox status and acetylcholinesterase activity in brain regions of the rats. DPDS may be a promising chemotherapeutic agent against brain injury resulting from CPF exposure.

This study investigated the effects of ethanol (EtOH) on manganese (Mn)-induced striatal toxicity in rat by evaluating the neurobehavioral changes, biochemical and molecular events in rats exposed to Mn alone at 30 mg/kg, or their combination with EtOH at 1.25- and 5-g/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were assessed using a video tracking software (ANY-Maze software) during a 5-min trial in a novel environment. Subsequently, acetylcholinesterase (AChE) activity, oxidative stress markers, histological morphology, and expression of apoptotic proteins (p53 and Bax and caspase-3) and anti-apoptotic protein (Bcl-2) were assessed in the striatum. Results showed that Mn, EtOH, and their combination induced locomotor and motor deficits. Track plot analysis indicated that EtOH exacerbated the Mn-induced reduction in exploratory profiles of exposed rats. Similarly, exposure of rats to Mn, EtOH, or combination of Mn and EtOH resulted in decreased activities of anti-oxidant enzymes, diminished level of reduced glutathione, downregulated Bcl-2 expression, increased AChE activity, enhanced hydrogen peroxide and lipid peroxidation levels, and upregulated expressions of p53, Bax, and caspase-3. Moreover, potentiation of Mn-induced striatal toxicity by EtOH co-exposure was dose dependent. Taken together, it seems that EtOH exacerbates Mn-induced neurobehavioral deficits, oxidative stress, and apoptosis induction via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway in rat striatum.

The diet is a major route of manganese (Mn) exposure for humans. Interestingly, several epidemiological data demonstrated an increase in the incidence of alcohol consumption globally. Chemical-chemical interaction subsequent to chemical mixtures exposure may result in a synergism or antagonism effects. The present study investigated the influence of co-exposure to ethanol (EtOH) and Mn on inflammation and apoptosis in the hypothalamus of rats. The study consisted of five groups of rats that were exposed to drinking water alone, EtOH alone at 5 g/kg, Mn alone at 30 mg/kg or co-expose with EtOH at 1.25 and 5 g/kg body weight by oral gavage for 35 consecutive days. The results indicated that the significant (p