Chlorpyrifos induced testicular damage in rats: Ameliorative effect of glutathione antioxidant

This study investigated the induction of oxidative stress in the testes of adult rats exposed to chlorpyrifos (CPF). CPF was administered orally, in a dose of 30 mg/kg body weight to male rats for 90 days, twice weekly. Coadministration of water‐soluble nonenzymatic antioxidant glutathione (GSH) was performed in a dose of 100 mg/kg body weight, orally, for the same period. Another two groups of male rats were administered GSH and corn oil, respectively. The activities of superoxide dismutase and GSH reductase were decreased while the levels of lipid peroxidation were increased in the testicular tissues of the exposed animals. Testosterone level in the serum was significantly decreased. A decrease in the histochemical determination of testicular alkaline phosphatase was observed in CPF‐treated rats. A significant decrease in all stages of spermatogenesis in the seminiferous tubules was recorded in the exposed animals. Coadministration of GSH restored these parameters. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 1011–1019, 2014.     

Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods

This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.     

Protective effects of Ziziphora tenuior extract against chlorpyrifos induced liver and lung toxicity in rat: Mechanistic approaches in subchronic study

Chlorpyrifos (CPF) is one of the most widely used organophosphorus, which has spurred renewed interest. This study was conducted to investigate the protective effect of ziziphora tenuior extract against CPF‐induced liver and lung toxicity. This study conducted 8‐week rat sub‐chronic toxicity study and then the effect of ziziphora tenuior extract in 3 different doses (40, 80, 160 mg/kg) was determined. We administrated maximum tolerated dose of CPF (6.75 mg/kg) by gavage for 8 weeks (5 times in week) to male rats. Rats were sacrificed 24 h after last dose and the biochemical analysis, which confirms involvement of oxidative stress in the pathogenesis of CPF toxicity in liver including increased in lipid peroxidation, protein carbonyl content, and ROS formation, glutathione depletion, decreased of antioxidant effect via frap oxidation and cytochrome c expulsion. In addition, pathological lesions confirm the dysfunction of the organs (liver and lung). In addition, using of ziziphora extract as an antioxidant is resulted in amelioration of oxidative stress marker in liver and lung damage. In conclusion, the current study revealed that CPF toxicity is related to oxidative stress and induction of cell death signaling and cotreatment with ziziphora extract is recommended in the routine therapy for the protection against CPF induced liver and lung tissue damage.     

Hydroxyl scavenging activity accounts for differential antioxidant protection of Plantago major against oxidative toxicity in isolated rat liver mitochondria

Objectives The aim of this work was to study the effects of P. major against the oxidative damage of isolated rat liver mitochondria. Methods The extracts were obtained using methanol (MeOH), ethyl acetate (EAc), dichloromethane (DCM), and hexane (Hex) as solvents. Key findings Hex, DCM, and EAc totally, and MeOH partially, inhibited ROS generation and lipid peroxidation of membranes induced by Fe²⁺ or t‐BOOH. However, only MeOH was able to prevent the t‐BOOH‐induced glutathione and NAD(P)H oxidation. All extracts chelated Fe²⁺ and reduced DPP Hradicals. EPR analysis revealed that P. major exhibited potent scavenger activity for hydroxyl radicals. Conclusions The potent antioxidant activity exhibited by P. major was able to prevent oxidative mitochondrial damage, contributing to the understanding of its hepatoprotective action against ROS‐mediated toxicity.     

Methylenedioxymethamphetamine inhibits mitochondrial complex I activity in mice: a possible mechanism underlying neurotoxicity

Background and purpose:

3,4-methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra of mice. Current evidence indicates that such neurotoxicity is due to oxidative stress but the source of free radicals remains unknown. Inhibition of mitochondrial electron transport chain complexes by MDMA was assessed as a possible source.

Experimental approach:

Activities of mitochondrial complexes after MDMA were evaluated spectrophotometrically. In situ visualization of superoxide production in the striatum was assessed by ethidium fluorescence and striatal dopamine levels were determined by HPLC as an index of dopaminergic toxicity.

Key results:

3,4-methylenedioxymethamphetamine decreased mitochondrial complex I activity in the striatum of mice, an effect accompanied by an increased production of superoxide radicals and the inhibition of endogenous aconitase. α-Lipoic acid prevented superoxide generation and long-term toxicity independent of any effect on complex I inhibition. These effects of α-lipoic acid were also associated with a significant increase of striatal glutathione levels. The relevance of glutathione was supported by reducing striatal glutathione content with L-buthionine-(S,R)-sulfoximine, which exacerbated MDMA-induced dopamine deficits, effects suppressed by α-lipoic acid. The nitric oxide synthase inhibitor, N^G-nitro-L-arginine, partially prevented MDMA-induced dopamine depletions, an effect reversed by L-arginine but not D-arginine. Finally, a direct relationship between mitochondrial complex I inhibition and long-term dopamine depletions was found in animals treated with MDMA in combination with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Conclusions and implications:

Inhibition of mitochondrial complex I following MDMA could be the source of free radicals responsible for oxidative stress and the consequent neurotoxicity of this drug in mice.This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers in this issue by Pravdic et al. and Kurz et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j.1476-5381.2010.00656.x     

Effect of dietary antioxidant on mercuric chloride induced lung toxicity and oxidative stress

This study was conducted to evaluate the effect of environmental contaminant mercuric chloride on levels of trace elements and oxidative parameters in rat lungs and to investigate the efficacy of possible protection by natural antioxidant diallylsulphide (DAS) against lung injury. Twenty-four healthy male rats were randomly divided into four groups: I – control, II – DAS (200?mg/kg), III – HgCl₂ (50?mg/kg), and IV – DAS (200?mg/kg) + HgCl₂ (50?mg/kg). Mercuric chloride induced oxidative stress was indicated by a significant decrease in levels of superoxide dismutase, catalase, and glutathione peroxidase as compared to the control group (p–<0.05). Also, hydroxyproline (HYP) content in lung tissues of mercuric chloride-treated group was significantly increased (p?<?0.05). DAS markedly attenuated mercuric-induced biochemical alterations in lungs by upregulating the activities of antioxidant enzymes. These findings indicated that within the doses selected, DAS can provide significant protection against HgCl₂-induced toxicity.     

A review of anti-inflammatory,antioxidant, and immunomodulatory effects of Allium cepa and its main constituents

ContextAllium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects.ObjectiveAnti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented.MethodsDatabases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory.ResultsA. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance).ConclusionsThe effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.     

Oxidative stress: a possible mechanism for lead-induced apoptosis and nephrotoxicity

Lead-induced nephrotoxicity is a human health hazard problem. In this study, Human mesangial cells (HMCs) were treated with different concentration of lead acetate (5, 10, 20 μmol/l) in order to investigate the oxidative stress and apoptotic changes. It was revealed that lead acetate could induce a progressive loss in HMCs viability together with a significant increase in the number of apoptotic cells using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay and flow cytometry, respectively. The apoptotic morphological changes induced by lead exposure in HMCs were demonstrated by PI-Hochest33342 staining. A DNA laddering pattern in lead-treated cells was shown, which could indicate nuclear fragmentation. In addition, lead acetate significantly increased the levels of malondialehyde (MDA) content and lactate dehydrogenase (LDH) activity. Therefore, it might be concluded that lead could promote HMCs’ oxidative stress and apoptosis, which may be the chief mechanisms of lead-induced nephrotoxicity.     

D-硝基精氨酸对小鼠肾损伤及氧化应激作用

目的研究D-硝基精氨酸(D-NNA)对小鼠的肾损伤及其氧化应激机制。方法 ICR小鼠ig给予D-NNA150,50和15 mg·kg-1,连续30 d。测定并计算肾系数;血液生化分析仪检测血清中肌酐(Crea)和尿素氮(BUN);分光光度法测定肾组织一氧化氮(NO),硫代巴比妥酸法测丙二醛(MDA)含量,比色法测定谷胱甘肽过氧化酶(GSH-Px)和超氧化物歧化酶(SOD)活性;观察肾病理组织学变化。结果与5%葡萄糖对照组相比,D-NNA 150,50和15 mg·kg-1组血清中BUN分别明显升高了83.6%,36.2%和27.4%(P<0.05),D-NNA150和50 mg·kg-1组血清中Crea分别明显升高了281.6%和10.6%(P<0.05);D-NNA150 mg·kg-1组肾系数和NO水平分别明显降低了5.6%和25.5%(P<0.05);D-NNA150和50 mg·kg-1组肾组织中MDA水平分别明显升高了69.0%和36.9%(P<0.01),SOD活性和GSH-Px活性分别明显下降了17.4%和17.7%,7.3%和13.7%(P<0.05);D-NNA150 mg·kg-1组病理检查可见肾小管损伤,嗜碱性变,萎缩或囊性扩张和间质炎性浸润,D-NNA50和15 mg·kg-1组出现炎症细胞浸润。结论 D-NNA对小鼠肾有一定的损伤作用,其作用机制可能与D-NNA的手性转化产物L-NNA导致NO合成减少,产生ROS有关。     

Crataegus Aronia protects and reverses vascular inflammation in a high fat diet rat model by an antioxidant mechanism and modulating serum levels of oxidized low-density lipoprotein

Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.

Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.

Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.

Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.

Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.     

Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant,anti-inflammatory,and neuroprotective intervention

Context: Emblica officinalis (Euphorbiaceae), commonly known as amla, is traditionally used for central nervous system (CNS) disorders.

Objective: In the present study, the effect of standardized hydroalcoholic extract of E. officinalis fruit (HAEEO), an Indian medicinal plant with potent antioxidant activity, was studied against kainic acid (KA)-induced seizures, cognitive deficits and on markers of oxidative stress.

Materials and methods: Rats were administered KA (10?mg/kg, i.p.) and observed for behavioral changes, incidence, and latency of convulsions over 4?h. The rats were thereafter sacrificed for estimation of oxidative stress parameters: thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH). The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was also determined in the rat brain.

Results: Pretreatment with HAEEO (500 and 700?mg/kg, i.p.) significantly (P?<?0.001) increased the latency of seizures as compared with the vehicle-treated KA group. HAEEO significantly prevented the increase in TBARS levels and ameliorated the fall in GSH. Furthermore, HAEEO dose-dependently attenuated the KA-induced increase in the TNF-α level in the brain. HAEEO also significantly improved the cognitive deficit induced by KA, as evidenced by increased latency in passive avoidance task.

Discussion and conclusion: HAEEO at the dose of 700?mg/kg, i.p., was most effective in suppressing KA-induced seizures, cognitive decline, and oxidative stress in the brain. These neuroprotective effects may be due to the antioxidant and anti-inflammatory effects of HAEEO.     

Effect of deltamethrin and fluoride co-exposure on the brain antioxidant status and cholinesterase activity in Wistar rats

The study evaluated the effect of commercial preparation of deltamethrin, Butox^®, and fluoride (F^?) co-exposure on the brain antioxidant status and cholinesterase activity in rats. Group A was untreated. Group B was gavaged Butox^®, providing deltamethrin at the dose rate of 1.28?mg per kg body weight per day. Group C was administered F^?, as NaF, in drinking water providing 20?ppm F^?. Group D received both deltamethrin and F^? at the same dosages as groups B and C, respectively. Although, glutathione S-transferase activity was induced only in Butox^® alone treated group, the activities of superoxide dismutase and catalase were inhibited in all treatment groups when compared to the control group. Elevated lipid peroxidation was observed in the groups exposed to F^?. The activity of erythrocyte acetylcholinesterase (AChE) was inhibited in Butox^® treated groups, whereas brain AChE activity was inhibited in all treatment groups. In conclusion, both deltamethrin (given as Butox^®) and F^? inhibit AChE activity and produce oxidative stress in brain with F^? producing more oxidative damage. However, compared to the individual exposures, the co-exposure of these chemicals does not produce any exacerbated alteration in these biochemical parameters.     

Neuroprotective effect of carvedilol against aluminium induced toxicity: possible behavioral and biochemical alterations in rats

Aluminium, is a trace element available in the Earth's crust naturally and has a toxic potential for humans. It has been suggested as a contributing factor in the pathogenesis of Alzheimer's disease. β-Adrenoceptor blocking agents (β-blockers) have been established as therapeutics for the treatment of patients with hypertension, ischemic heart diseases, chronic heart failure, arrhythmias and glaucoma. Over the years, however, β-blockers have been associated with an incidence, albeit low, of central nervous system (CNS) side effects. In addition, noradrenergic receptors play a modulatory role in many nerve functions, including vigilance, attention, reward, learning and memory. Therefore, the present study has been designed to explore the possible role of carvedilol, an adrenergic antagonist against aluminium chloride-induced neurotoxicity in rats. Aluminium chloride (100 mg/kg) was administered daily for six weeks that significantly increased cognitive dysfunction in the Morris water maze and oxidative damage as indicated by a rise in lipid peroxidation and nitrite concentration and depleted reduced glutathione, superoxide dismutase, catalase and glutathione S-transferase activity compared to sham treatment. Chronic aluminium chloride treatment also significantly increased acetylcholinesterase activity and the aluminium concentration in brain compared to sham. Chronic administration of carvedilol (2.5 and 5 mg/kg, po) daily to rats for a period of 6 weeks significantly improved the memory performance tasks of rats in the Morris water maze test, attenuated oxidative stress (reduced lipid peroxidation, nitrite concentration and restored reduced glutathione, superoxide dismutase, catalase and glutathione S-transferase activity), decreased acetylcholinesterase activity and aluminium concentration in aluminium-treated rats compared to control rats (p < 0.05). Results of this study demonstrated the neuroprotective potential of carvedilol in aluminium chloride-induced cognitive dysfunction and oxidative damage.     

The toxicological effects of nano titanium dioxide on target organs and mechanisms of toxicity

Nano-titanium dioxide (TiO₂NPs) is widely used for its extremely high stability, corrosion resistance, and photocatalytic properties and has penetrated into various fields of production and life. Assessing its toxicity to different organs should be a key part of preclinical toxicity assessment of TiO₂NPs, which is relatively incomprehensive yet. Therefore, this review focuses on the toxic effects of TiO₂NPs on various organs in mammals and biological mechanisms from different organs. The commonality of toxic effects on various target organs reflected in tissue structure damage and dysfunction, such as liver damage and dysfunction; pulmonary fibrosis; and renal impairment (including hematuria and nephritis); damage of brain tissue and neurons; alteration of intestinal villi; and weight loss. And effects on the reproductive system are affected by different sexes, including ovarian dysfunction, testicular development damage, and sperm viability reduction. We believe that the toxic mechanisms of TiO₂NPs in target organs have commonalities, such as oxidative stress, inflammatory responses, and organelle damage. However, different target organ toxicities also have their specificities. TiO₂NPs disturb the intestinal flora and cause undesirable changes in feces products. And in spleen are infiltration of neutrophils and lymphadenopathy and eventually immune deficiency. Although the toxic pathways are different, but there may be a close link between the different toxic pathways. In this article, the main manifestations of the toxic effects of titanium dioxide nanoparticles on major mammalian organs are reviewed, in order to provide basic data for their better application from a medical perspective.     

Reduction in antioxidant defenses may contribute to ochratoxin A toxicity and carcinogenicity.

Ochratoxin A (OTA) is a renal carcinogen in rodents. Its human health significance is unclear. It likely depends upon the mechanism of carcinogenesis. In a previous microarray study a reduction in nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-dependent gene expression was observed in the kidney but not in the liver of rats fed OTA up to 12 months. Nrf2 regulates detoxification and antioxidant gene expression. The present report shows that OTA decreased the protein expression of several markers of the Nrf2-regulated gene battery in kidney in vivo indicating that the effects observed at mRNA level may be of biological significance. The OTA-mediated Nrf2 response could be reproduced in an NRK renal cell line and in primary hepatocyte cultures. In in vitro systems, an OTA-mediated inhibition of Nrf2 activity was demonstrated by electrophoretic mobility shift and Antioxidant Regulatory Element-driven luciferase reporter assays. The reduction of Nrf2-regulated gene expression resulted in oxidative DNA damage as evidenced by formation of abasic sites in vitro and confirmed in kidney in vivo. All OTA-mediated effects observed were prevented by pretreatment of cell cultures with inducers of Nrf2 activity. Our data suggest that reduction of cellular defense against oxidative stress by Nrf2 inhibition may be a plausible mechanism of OTA nephrotoxicity and carcinogenicity.     

Antidiabetic and antioxidant activity of the methanol extract of Diospyros peregrina fruit on Type I diabetic rats

Chronic diabetes complications are mainly associated with augmented oxidative stress. Thus the present study evaluated the hypoglycemic, as well the antioxidant effect, of the methanol extract of Diospyros peregrina Gurke. (Ebenaceae) fruits on experimental diabetic rats. Oral administration of methanol extract at 150 and 300?mg/kg body weight per day to diabetic rats was found to have profound hypoglycemic activity in term of reduction of fasting blood glucose level. The diabetic rats showed lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract-treated diabetic rats in selected tissues. The increased levels of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) in diabetic rats were also found to be reverted back to near-normal status in extract-treated groups. It was found that the extract is more effective at the dose of 300?mg/kg body weight and this effect is almost comparable to that of standard glibenclamide.     

昆虫抗菌肽抗炎活性及基于信号通路抗炎机制的研究进展

昆虫抗菌肽是昆虫为抵御外界病原微生物感染产生的免疫活性物质的总称,其优异的抗炎活性使其具有广阔的应用前景。综述了不同种类昆虫抗菌肽的抗炎活性及可能涉及的信号通路,介绍了昆虫抗菌肽临床研究现状,以期为昆虫抗菌肽的应用研究提供文献参考。     

Glycyrrhizic acid and silymarin alleviate the neurotoxic effects of aluminum in rats challenged with fructose-induced insulin resistance: possible role of toll-like receptor 4 pathway

Aluminum is implicated in the etiology of different neurodegenerative diseases, diabetes and cancer. The current study was conducted to evaluate the protective effects of glycyrrhizic acid (GAM) and silymarin (SLY) on AlCl₃-induced neurotoxicity in insulin resistant rats. Insulin resistance (IR) was induced by fructose (10%) in drinking water for 18 weeks. Rats received AlCl₃ (34?mg/kg/day) with or without fructose, GAM (40?mg/kg/day), or SLY (100?mg/kg/day). The administration of GAM or SLY suppressed AlCl₃-induced memory deficit, oxidative stress, and neuroinflammation in brain tissue of IR rats. Both agents inhibited AlCl₃-induced activation of TLR4 signaling pathway including the downstream activation of NF-κB. The results show that IR can partly exacerbate AlCl₃-induced neurotoxicity, particularly memory deficit and neuroinflammation. In addition, GAM and SLY showed promising neuroprotective effect against AlCl₃-induced brain damage in IR rats. The neuroprotection induced by these natural products might be mediated through their antioxidant and anti-inflammatory effects. The latter effect seems to be mediated via inhibition of TLR4 signaling pathway providing new insights on the mechanisms implicated in AlCl₃-induced neurotoxicity and the neuroprotection afforded by GAM and SLY.     

Nicotine induced pro-oxidant and antioxidant imbalance in rat lymphocytes: in vivo dose and time dependent approaches

The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The present study was undertaken to determine the dose as well as time dependent effects of nicotine administration on the superoxide anion generation, lipid peroxidation and antioxidant defense systems in lymphocytes. Male Wistar rats were treated with vehicle (normal saline) and nicotine [3-(1-methyl-2-pyrrolidinyl) pyridine, C₁₀H₁₄N₂] (in physiological saline, pH was adjusted at 7.4 prior to injection) as indicated in a dose and duration fashion and the superoxide anion generation, lipid peroxidation, and antioxidant enzymes status were monitored. Superoxide anion generation, lipid peroxidation and oxidized glutathione levels were increased significantly (P < 0.05), and reduced glutathione level, activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-s-transferase were decreased significantly (P < 0.05) with the increasing dose and duration of nicotine treatment. The highest changes in lymphocytes were observed at the dose of 1.0?mg/kg/day for 7 days. It may be concluded that nicotine is able to enhance the production of ROS that produced oxidative stress in lymphocytes in a dose and time dependent manner.