Search

Risperidone is an atypical antipsychotic drug used for the pharmacotherapy of psychiatric disorders. Some reports indicate that risperidone is toxic to various systems of the body, including the immune system. This study evaluated the toxicity effect of risperidone on human blood lymphocytes. To achieve this aim, lymphocytes were isolated using Ficoll paque plus. The results showed that risperidone (12, 24 and 48 nM) causes toxicity in human blood lymphocytes by increasing the level of intracellular reactive oxygen species (ROS), damage to lysosomal membrane, the collapse of the mitochondrial membrane potential (MMP), and increased extracellular oxidized glutathione (GSSG). Also, exposure of human blood lymphocytes to risperidone is associated with a decrease in intracellular glutathione (GSH) levels. Finally, it could be concluded that oxidative stress is one of the mechanisms of risperidone-induced toxicity in human blood lymphocytes.

Objectives Rhus coriaria L. (RC) is a deciduous shrub with several pharmacological activities. Evidence of the effects of RC on weight, hyperlipidaemia, hypertension and diabetes mellitus have been presented in this study. Books, thesis and internet-based resources such as PubMed, Web of Science, Scopus, EMBASE, Cochrane, Ovid and Google Scholar were searched for the English, Arabic and Persian literature from 1966 to 2020 (December). The keywords were Rhus coriaria L., Sumac, metabolic syndrome and all its medical conditions (hyperlipidaemia, hypertension, obesity and diabetes mellitus). The inclusion criteria were full-text animal and human studies conducted on RC to evaluate its efficacy on any components of metabolic syndrome (MetS). Jadad scale was used to assess the quality of evidence. Key findings Reviewing 23 relevant studies demonstrated that RC is able to decrease the level of blood glucose, glycated haemoglobin, serum insulin and insulin resistance. Studies on hyperlipidaemia and obesity have very contradicting results, and there is no definite conclusion on the effect of RC on lipid profile. However, the hypotensive and effect of RC was confirmed in the existing studies. Summary According to the literature, RC can be considered as a promising curative candidate for MetS. However, further studies with larger sample size and higher methodological quality are needed.

ObjectivesIris germanica L. is a medicinal plant, which has a long history of uses, mainly in medieval Persia and many places worldwide for the management of a wide variety of diseases. In this study, we aimed to review ethnopharmacological applications in addition to phytochemical and pharmacological properties of I. germanica.Key findingsEthnomedical uses of I. germanica have been reported from many countries such as China, Pakistan, India, Iran and Turkey. The medicinal part of I. germanica is the rhizome and the roots. Based on phytochemical investigations, different bioactive compounds, including flavonoids, triterpenes, sterols, phenolics, ceramides and benzoquinones, have been identified in its medicinal parts. Current pharmacological studies represent that the plant possesses several biological and therapeutic effects, including neuroprotective, hypoglycaemic, hypolipidaemic, antimicrobial, antioxidant, antiproliferative, anti-inflammatory, antiplasmodial, antifungal, immunomodulatory, cytotoxic and antimutagenic effects.SummaryAlthough the majority of preclinical studies reported various pharmacological activities of this plant, however, sufficient clinical trials are not currently available. Therefore, to draw a definitive conclusion about the efficacy and therapeutic activities of I. germanica and its bioactive compounds, further clinical and experimental studies are required. Moreover, it is necessary to focus on the pharmacokinetic and safety studies on the extracts of I. germanica.

Food contaminants are one of the most important and concerning issues worldwide. Protecting the public from the harm of contaminated foods has become a daunting task. On the other hand, the elimination of these contaminants from food seems impossible. Therefore, one of the best solutions is to recommend inexpensive and publicly available food additives like many spices used in food as flavoring and coloring. Curcuma longa or turmeric is one of the well-known spice, which confers many medicinal properties. Curcumin is the main active ingredient in turmeric, which has many health benefits. Recent research has revealed that turmeric/curcumin has protective effects against toxicants, mostly natural and chemical toxins. In this review article, we reviewed studies related to the protective effects of turmeric and its active ingredient against food contaminants.

Alzheimer's disease is the most common form of dementia among the elderly. This progressive neurodegenerative disorder affects brain regions that control cognition, memory, language, speech, and awareness. As a potent antioxidant, crocin has been proposed to effectively manage the neurodegenerative disease. In this study, the recovery effects of crocin on the memory deficits caused by the intra-hippocampal injection of amyloid beta1-42 (Aβ1-42) were evaluated in rats. We also considered the protective effects of crocin on the mitochondrial damage caused by Aβ1-42. We examined the memory deficits of rats with the help of the Morris water maze. Then, we determined different mitochondrial toxicity endpoints caused by Aβ1-42, including mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity, and cytochrome c release. Our results demonstrated that the behavioral signs of memory deficiency caused by Aβ1-42 significantly (

Lithium (Li) is a widely-used medication for the treatment of patients with bipolar disorder. Li causes different complications. One of the most important adverse effects of Li is neurotoxicity. Neurotoxicity is usually irreversible which may lead to very important complications. The symptoms of Li-induced neurotoxicity include tremor, delirium, seizures, coma, and death. In this study, we wanted to evaluate the exact sub-cellular mechanisms of Li-induced neurotoxicity. For this purpose, we used primary neuronal cortical culture for investigating lithium-induced neurotoxicity. We applied the postnatal rat pups for isolating the cortical neurons. After that, we evaluated neural viability, neural reactive oxygen specious (ROS), lipid peroxidation, mitochondrial membrane potential (MMP), lysosomal membrane integrity (LMI), and reduced (GSH) and oxidized (GSSG) glutathione. Our results demonstrated that the cytotoxic effect of Li has mediated through lysosomal membrane leakage associated with ROS formation and reduction of MMP. Furthermore, the incubation of isolated neurons with Li caused rapid GSH depletion (as GSSG efflux) as another marker of cellular oxidative stress. We concluded that Li causes neurotoxicity in a dose-dependent manner. Besides, Li-induced neurotoxicity is a result of the generation of ROS and LP, which leads to mitochondrial/lysosomal toxic cross-talk.

Objectives Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

Alzheimer's disease (AD) is one of the most important causes of dementia, especially in the elderlies. Due to the failures of recent clinical trials in finding effective medications, it appears the use of complementary therapies such as Traditional Persian Medicine (TPM) and the rich sources of effective herbs as well as their constituents for improving memory function could be beneficial. The aim of this study was to evaluate the recommended natural remedies in the TPM and examine their pharmacological properties. For this purpose, the data were collected by searching the recommended prescriptions of the seminal TPM textbooks. Then, the names of the most freuqently mentioned plants were extracted from the natural remedies and evaluated for their pharmacological properties. The sources included recently published articles cited in the major scientific databases. A total of 262 plants were identified in 96 evaluated prescriptions; 20 plants were identified with the most frequency of report (i.e. more than 10 times). Their neuroprotective effects, antioxidant features, and anti-AD properties were discussed. Based on our results, TPM has introduced many effective treatments for AD. Hence, more clinical studies are warranted to verify their efficacy and safety.

Alzheimer’s disease (AD) is one of the most important causes of dementia, especially in the elderlies. Due to the failures of recent clinical trials in finding effective medications, it appears the use of complementary therapies such as Traditional Persian Medicine (TPM) and the rich sources of effective herbs as well as their constituents for improving memory function could be beneficial. The aim of this study was to evaluate the recommended natural remedies in the TPM and examine their pharmacological properties. For this purpose, the data were collected by searching the recommended prescriptions of the seminal TPM textbooks. Then, the names of the most freuqently mentioned plants were extracted from the natural remedies and evaluated for their pharmacological properties. The sources included recently published articles cited in the major scientific databases. A total of 262 plants were identified in 96 evaluated prescriptions; 20 plants were identified with the most frequency of report (i.e. more than 10 times). Their neuroprotective effects, antioxidant features, and anti-AD properties were discussed. Based on our results, TPM has introduced many effective treatments for AD. Hence, more clinical studies are warranted to verify their efficacy and safety.

Mitochondria are one of the most important subcellular organelles that play important roles in cell function. They are double membrane–bound organelles responsible for many processes in eukaryotic cells, such as the production of adenosine triphosphate (ATP). Mitochondria are the main site of ROS production. They are responsible for cellular death, regulation of calcium hemostasis, and immunity. Recent researches demonstrated that mitochondria play a key role for aging. In recent years, nutritional approaches have been considered as possible alternatives to the currently existing medications to increase the response to therapy. Based on many studies, the positive effect of fasting on health and the prevention of many diseases has been confirmed. This section of the book explains the mitochondrial mechanisms of aging and the effects of diet on it.

Nitrite and nitrite are considered hazardous, and there are legal limits to their concentration in food and drinking water. The typical diet in most countries contains nitrites, nitrites, and nitrosamines. It is used as a food preservative, especially in cured meats. In this research, we investigated the cytotoxic mechanisms of sodium nitrite in isolated hepatocyte. For this purpose, we evaluated the several oxidative stress markers. The results showed that the cytotoxicity of sodium nitrite on hepatocytes was associated with reactive oxygen species (ROS) formation and lipid peroxidation which were inhibited by antioxidants and ROS scavengers, mitochondrial permeability transition, pore sealing agents and endocytosis inhibitors. Sodium nitrite cytotoxicity was also associated with mitochondrial injury, lysosomal membrane rupture and release of digestive proteases which were prevented by antioxidants, mitochondrial permeability transition (MPT) pore sealing agents and lysosomotropic agents. In conclusion, sodium nitrite at concentration of 5 mM could have cytotoxic effects on isolated rat hepatocytes by above mentioned mechanisms.

In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential (MMP) collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25 µg/ml significantly (p

Cyclophosphamide (CYP) and methotrexate (MTX) have been evaluated for their ability to induce toxicity in human peripheral blood lymphocytes (PBLs) and the protective role of mitochondrial and lysosomal stabilizing agents. The potential toxicity effects of CYP and MTX were measured in vitro by cellular parameters assays such as cellular viability, reactive oxygen species (ROS) formation, mitochondrial membrane permeability transition (mitochondrial membrane potential (MMP)) collapse, lysosomal membrane damage, intracellular reduced glutathione (GSH), extracellular oxidized glutathione (GSSG), and lipid peroxidation. Separately, human lymphocytes were treated with concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 ng/mL for CYP and 1, 2, 5, and 10 µg/mL for MTX for 6 h. Statistical evaluations showed that CYP and MTX significantly decreased the cell viability at the three highest concentrations when compared with both the negative and solvent controls. In addition, CYP and MTX were significantly induced ROS formation, MMP collapse, lysosomal membrane damage, lipid peroxidation, and GSH depletion compared with the controls. Mitochondrial and lysosomal protective agents like cyclosporine A and chloroquine, respectively, decreased cytotoxicity and oxidative stress induced by CYP and MTX. The present results indicate that CYP and MTX are toxic to human PBLs and their toxicity could be ameliorated by mitochondrial and lysosomal protective agents.

Crocin, the main constituent of saffron (Crocus sativus L.), is a natural carotenoid which is known for its antioxidant activity. Liver as the organ that metabolizes many chemicals is one of the first position that is at risk of environmental pollutants. It is clear that compounds that exhibit antioxidant properties, scavenging of free radicals and inhibition of lipid peroxidation are expected to show hepatoprotective effects. Previous studies have proven the protective effect of crocin on the liver. The aim of this study is to find out the exact hepatoprotective mechanisms of this compound. In the present study, the protective effects of various concentrations of crocin (5, 10, 25, 50 and 100 μg/mL) were examined against oxidative stress toxicity induced by cumene hydroperoxide (CHP) on isolated rat hepatocytes. To find out the exact protective activity of crocin, we evaluated cell lysis, lipid peroxidation, reactive oxygen species (ROS) generation, GSH/GSSG, collapse of mitochondrial membrane potential, lysosomal membrane damage, the release of cytochrome c, and cellular proteolysis. Crocin (50 and 100 µg/mL) reduces cell lysis, lipid peroxidation, ROS generation, collapse of mitochondrial membrane potential, lysosomal membrane damage, cytochrome c release, and cellular proteolysis. It also increase GSH/GSSG. Crocin (50 and 100 µg/mL) reduced liver toxicity not only as an antioxidant but also by protecting the mitochondria and lysosome. Our data demonstrated that crocin is a promising candidate for preventing liver injury associated with oxidative stress. These findings pave the way to further studies evaluating the clinical protective effect of crocin.

Aluminum phosphide (AlP) poisoning is a severe toxicity with 30-70% mortality rate. However, several case reports presented AlP-poisoned patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and extensive hemolysis who survived the toxicity. This brought to our mind that maybe G6PD deficiency could protect the patients from severe fatal poisoning by this pesticide. In this research, we investigated the protective effect of 6-aminonicotinamide (6-AN)- as a well-established inhibitor of the NADP+- dependent enzyme 6-phosphogluconate dehydrogenase- on isolated rat hepatocytes in AlP poisoning. Hepatocytes were isolated by collagenase perfusion method and incubated into three different flasks: control, AlP, and 6-AN+ALP. Cellar parameters such as cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential collapse (MMP), lysosomal integrity, content of reduced (GSH) and oxidized glutathione (GSSG) and lipid peroxidation were assayed at intervals. All analyzed cellular parameters significantly decreased in the third group (6-AN+AlP) compared to the second group (AlP), showing the fact that G6PD deficiency induced by 6-AN had a significant protective effect on the hepatocytes. It was concluded that G6PD deficiency significantly reduced the hepatotoxicity of AlP. Future drugs with the power to induce such deficiency may be promising in treatment of AlP poisoning.

Perfluorooctanesulfonate (PFOS), an anthropogenic fluorosurfactant, is one of the most common global pollutants. PFOS is used in various consumer products to provide soil, oil, and water resistance to materials used in clothing, upholstery, and food packaging. PFOS is persistent, bioaccumulative, and toxic to mammalian species. In this study, the cellular mechanisms involved in PFOS hepatotoxicity were evaluated. For this purpose, we determined oxidative stress markers including cell lysis, ROS generation, lipid peroxidation, glutathione depletion, mitochondrial membrane potential decrease, lysosomal membrane leakiness, and cellular proteolysis. Our results demonstrated that PFOS liver cytotoxicity was associated with reactive oxygen species (ROS) formation and lipid peroxidation in isolated rat hepatocytes. Incubation of hepatocytes with PFOS caused rapid depletion of hepatocyte glutathione (GSH), an important marker of cellular oxidative stress. Most of the PFOS-induced GSH depletion could be attributed to the expulsion of glutathione disulfide (GSSG). PFOS hepatotoxicity was inhibited by antioxidants and ROS scavengers, mitochondrial permeability transition (MPT) pore sealing agents, and endocytosis inhibitors. Our results suggest that PFOS hepatotoxicity might be the result of oxidative stress-induced lysosomal membrane leakiness and cellular proteolysis in rat hepatocytes.

Hexachlorobutadiene (HCBD) is a potent nephrotoxin which nowadays contaminates human foods and water. On the other hands, it has been reported that rutin is a chemopreventive flavonoid which exerts some protective effects on the kidney. Therefore, in this work, the possible effect of rutin on HCBD-induced nephrotoxicity was investigated in female rats. The animals were divided into five groups. Groups 1 and 2 were treated with vehicle and HCBD (100 mg/kg, i.p.), respectively. Groups 3-5 were pretreated with rutin (100, 500 and 1000 mg/kg, i.p.) 1 h before HCBD injection. The level of serum urea and creatinine as well as urinary glucose and protein were measured. Total thiol content and lipid peroxidation level were also determined in the kidney homogenate. When compared to control group, a significant increase in the level of serum creatinine and urea (p 0.001) as well as urine glucose and protein (p 0.001) were observed after 24 h of HCBD administration. HCBD also caused a significant decrease in total thiol content (p 0.001) and a significant increase in lipid peroxidation level (p 0.001). Pretreatment with rutin could decrease serum creatinine (p 0.001) and urea (p 0.001) as well as urine protein (p 0.001) concentrations when compared with HCBD treated rats. No significant modification on urine glucose was seen (p 0.05). Rutin also reversed the HCBD-induced depletion in thiol content (p 0.001) and elevation in lipid peroxidation (p 0.001) in the kidney. The results of present study showed that rutin clearly attenuated HCBD-induced nephrotoxicity and has the potential to be considered as a nephroprotective agent.

In this study, a novel approach is proposed for determination of methylphenidate in biological fluids. In this method molecularly imprinted solid-phase extraction (MISPE), as the sample extraction technique, combined with high-performance liquid chromatography (HPLC) is used. The water-compatible molecularly imprinted polymers (MIPs) were prepared using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linker, Hexane as porogen and methylphenidate as template molecule. Extraction of methylphenidate from human serum was carried out using a novel imprinted polymer as the solid-phase extraction (SPE). Various parameters affecting the extraction efficiency of the polymer were evaluated. Also, the optimal conditions for the MIP cartridges were studied. The limit of detection (LOD) and limit of quantification (LOQ) for methylphenidate in serum samples were 1.3 and 10 ng mL-1, respectively. The recoveries for serum samples were higher than 92%.