PROTECTIVE EFFECTS OF MANGANESE AGAINST LIPID PEROXIDATION

The aim of this study was to investigate the effects of chronic, daily, 30-d administration of manganese chloride (MnCl₂) to male Sprague-Dawley rats on lipid peroxidation in various tissues. Rats were intraperitoneally injected with MnCl₂ (20 mg/kg) once daily for 30 con secutive days. The Mn accumulated in liver, spleen, adrenal glands, heart, kidneys, lung, and testes. This was associated with decreased lipid peroxidation in liver, spleen, and adrenal glands and a decrease in the levels of Fe in these tissues. In a second group of animals, Mn (20 mg/kg/d) and glutathione (GSH, 15 mg/kg/d) were administered ip for 30 d. GSH counteracted the Mn-induced protective fall in lipid peroxidation, but Fe levels remained lower in liver and spleen. Mn decreases lipid peroxidation in certain tissues, which may involve lowering Fe content, but interaction with Fe is not the sole mechanism.     

Brain lipid peroxidation and changes of trace metals in rats following chronic manganese chloride exposure

The aim of this study was to investigate the effects of chronic, daily, 30-d administration of manganese chloride (MnCl2) to male Sprague-Dawley rats on lipid peroxidation and changes of trace elements (manganese, iron, copper, zinc) in various brain regions. Rats were intraperitoneally injected with MnCl2 (20 mg/kg) once daily for 30 consecutive days. The Mn accumulated in frontal cortex, corpus callosum, hippocampus, striatum, hypothalamus, medulla, cerebellum, and spinal cord. Malondialdehyde, an end product of lipid peroxidation, was markedly decreased in frontal cortex and cerebellum. An increased level of Cu was observed in frontal cortex, medulla, and a cerebellum. A decreased Fe level was found only in cerebellum, and a decreased Zn level was observed in hippocampus and striatum. In a second group of animals, Mn (20 mg/kg/d) and glutathione (GSH, 15 mg/kg/d) were administered ip for 30 d. In CSH-Mn-treated rats, compared to Mn-treated rats, MDA concentrations were significantly reduced in frontal cortex, medulla and cerebellum. The changes of trace elements in rat brain were similar to the Mn-treated group. We suggest that Mn is an atypical antioxidant, as well as not involved in oxidative damage in rat brain. Fe and Cu may play roles in the protective effect of Mn against lipid peroxidation in rat brain.     

Lipid peroxidation in the liver of dogs and guinea pigs receiving chloditan

The contents and the rates of the formation of lipid peroxides in the liver homogenates were studied. Dogs and guinea pigs were fed with chloditan in doses of 50 and 150 mg/kg body weight, respectively, for 20 days. In the dogs chloditan caused atrophy of the adrenal glands. The drug accumulation in the adrenal glands of the guinea pigs did not produce damage of the glands. The feeding with chloditan failed to change the level of malondialdehyde in the livers of the dogs and decreased it in the livers of the guinea pigs. In vitro spontaneous and NADP N-dependent lipid peroxidation in the liver homogenates of the dogs treated with chloditan was slowed. The decrease of malondialdehyde content in the guinea pig liver and the slowing of lipid peroxidation rate in the dog liver homogenate can be explained by the change in the activity of the enzymes detoxicating xenobiotics and products of lipid peroxidation.     

Manganese-induced single strand breaks of mitochondrial DNA in vitro and in vivo

The aim of this study was to examine the single strand breaks (SSB) of mitochondrial DNA (mtDNA) induced by MnCl(2) in vitro and in vivo and discuss the possible underlying mechanism. In in vitro study the formation of mtDNA SSB and reactive oxygen species (ROS) in isolated hepatic mitochondria treated with MnCl(2) (0-1.0mmolL(-1)) was observed. In in vivo study the SSB of brain and liver mtDNA was examined, meanwhile the level of glutathione (GSH) and malondialdehyde (MDA) and activity of antioxidant enzymes were examined after 3-month intraperitoneal administration of MnCl(2) daily (0, 5, 10 and 20mg/kg/d) in Sprague-Dawley rats. The in vitro results indicated that MnCl(2) increased the formation of mtDNA SSB and ROS in **a dose-dependent manner in vitro. MnCl(2) exposure in vivo increased in mtDNA SSB in rat brain and liver and decreased in level of GSH in rat hepatic mitochondria and brain homogenates in a dose-dependent manner. The level of MDA and the activities of SOD and GPx were not significantly changed in both hepatic mitochondria and brain homogenates of rats. These results indicated that Mn treatment increased in mtDNA SSB in vitro and in vivo, mediated probably via Mn-induced oxidative stress.     

Comparative study of natural antioxidants - curcumin, resveratrol and melatonin - in cadmium-induced oxidative damage in mice

The present study was designed to examine the antioxidative effect of curcumin, resveratrol and melatonin pre-treatment on cadmium-induced oxidative damage and cadmium distribution in an experimental model in mice. Male CD mice were treated once daily for 3 days with curcumin (50mg/kg b.w., p.o.), resveratrol (20mg/kg b.w., p.o.) or melatonin (12mg/kg, p.o.), dispersed in 0.5% methylcellulose. One hour after the last dose of antioxidants cadmium chloride was administered (7mg/kg b.w., s.c.) to pre-treated animals and control animals receiving methylcellulose. At 24th h after Cd administration the lipid peroxidation (LP - expressed as malondialdehyde production), reduced glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx) were estimated in liver homogenates. Cadmium concentration was measured in the liver, kidneys, testes and brain by AAS. Cadmium chloride administration to mice induced hepatic lipid peroxidation (to 133%, p<0.001), decreased GSH content (to 65%, p<0.001) and inhibited catalase (to 68%, p<0.001) and GPx activity (to 60%, p<0.001) in the liver. Curcumin, resveratrol and melatonin oral pre-treatment completely prevented the Cd-induced lipid peroxidation and Cd-induced inhibition of GPx hepatic activity. Resveratrol was effective against Cd-induced inhibition of catalase activity (p<0.001). The decrease in hepatic GSH level was not prevented by curcumin, resveratrol or melatonin pre-treatment. In mice treated with antioxidants alone the level of LP, GSH, GPx or CAT was not different from control levels. The pre-treatment with antioxidants did not affect cadmium distribution in the tissues of Cd-intoxicated mice. The results demonstrate that curcumin, resveratrol and melatonin pre-treatment effectively protect against cadmium-induced lipid peroxidation and ameliorate the adverse effect of cadmium on antioxidant status without any reduction in tissue Cd burden.     

Stimulation of lipid peroxidation and impairment of glutathione-dependent defense system in Wistar rats treated with cryptopine, a rare non-narcotic opium alkaloid.

The present study was designed to evaluate the effect of repeated oral administration of cryptopine at differential dosing regimens (50, 100, 150, 200 mg/kg bwt) in vivo on lipid peroxide measures, glutathione levels (GSH) and activity of glutathione S-transferase (GST) and glutathione reductase (GR) in the liver, spleen, kidney and lung of Male Wistar rats after a 5 day treatment period. In all the tissues examined, we observed an increase in lipid peroxidation and a decline in glutathione content and activity of glutathione S-transferase and glutathione reductase in a dose-dependent manner. The decrease in GSH content did not definitively correlate with a concomitant increase of lipid peroxidation in all the tissues. Our results ensemble that the enhancement of lipid peroxidation in the tissues investigated is a consequence of depletion of glutathione to certain critical levels and impairment of the glutathione-dependent enzyme systems viz. GST and GR. Our study potentiates that decreased levels of GSH may lead to lipid peroxidation, one of the key events in cellular damage. The inhibition of GST also suggests that the detoxification of the alkaloid could be suppressed following acute exposures. Conclusively, it appears that cryptopine in vivo disturbs the cellular defense system, so that it tips in the direction of autoxidative lipid peroxidation, producing cytotoxicity.     

Induction of lipid peroxidation in tissues of thallous malonate-treated hamster

Thallous malonate was administered orally to hamsters in a single dose of 10 mg Tl/kg or 50 mg Tl/kg body weight. After 1 day and 3 days the levels of lipid peroxidation and non-protein sulfhydryls (NPSH) and glutathione peroxidase (GSH-Px) activity in tissues were measured. At a thallium dose of 10 mg/kg, increases in lipid peroxidation were already apparent in the kidney after 1 day. On the other hand, a marked increase in lipid peroxidation with decrease in NPSH content and GSH-Px activity in the kidney and liver were found 3 days after administration of the 50 mg Tl/kg dose, and renal and liver damage also developed. These results suggested that thallous malonate-induced tissue damage may be associated with the development of peroxidative processes caused by depression of GSH and inhibition of the GSH-Px activity-linked defensive system.     

枸杞子多糖对物理应激刺激和四氯化碳所致组织脂质代谢异常的保护作用(英文)

本文观察了长期电击加低剂量γ射线照射对5月龄大鼠肝、脾和大脑皮层脂质过氧化作用的影响以及枸杞子多糖的保护效应。长期应激刺激(12wk)后。大鼠脾重指数明显降低(p<0.01),而大脑皮层指数显著升高(p<0.01)。应激刺激还使脾和大脑皮层总脂含量明显降低(p<0.001),脂质过氧化物(MDA)较对照组显著升高(p<0.05)。于实验第7wk,另15只应激大鼠枸杞子多糖ip 5mg/kg(n=10)和10 mg/kg(n=5),5次/2周,共给药15次。给药组脾和脑勺浆总脂水平与对照组接近,同时脾匀浆MDA含量显著降低(p<0.001)。另外,枸杞子多糖10.50 mg/kg(每天一次,共一周)对四氯化碳(256 mg/kg,po)导致的小鼠肝脂质过氧化损伤亦起到明显的保护作用。这些结果提示枸杞子多糖具有调节脂质代谢的效应,其抗脂质过氧化作用的机理有待深入研究。     

Alteration of humoral and cellular immunity in manganese chloride-treated mice

Immunological effects of manganese chloride (MnCl2) were determined in male CD-1 mice injected (ip) daily with MnCl2 (0, 1, 3, or 10 mg/kg) for 4 wk. Liver and spleen weights increased in the 10-mg/kg MnCl2 treatment group. The weights of thymus, kidney, and adrenal glands were not affected by MnCl2 treatment. No significant differences in peripheral erythrocyte or leukocyte counts were observed; however, packed cell volumes decreased in the medium- and high-dose groups. Manganese treatment significantly increased the uptake of [3H]thymidine (3H-TdR) by cultured splenic cells. The lymphoproliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A) increased at all levels of MnCl2 exposure. No differences in the responses to lipopolysaccharide (LPS) were observed. Mixed lymphocyte responses increased significantly with exposure to 10 mg MnCl2/kg. Another immunological alteration induced by MnCl2 was a dose-dependent immunosuppressive effect on the development of antibody-forming cells. The production of anti-sheep red blood cell antibody (alpha-SRBC) nearly ceased following exposure to 10 mg MnCl2/kg. This effect was apparently reversible, as the number of plaque-forming cells in the 10-mg/kg treatment group increased after MnCl2 treatment had been halted for 2 wk. The alpha-SRBC titer also decreased significantly in the 10-mg/kg treatment group, corresponding to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory to the reduction of antibody producing cells. MnCl2 treatment was immunomodulatory in male CD-1 mice, as indicated by the increase in mitogen and mixed lymphocyte responses and decrease in antibody production.     

Dietary α-tocopherol prevents dehydroepiandrosterone-induced lipid peroxidation in rat liver microsomes and mitochondria

Dehydroepiandrosterone (DHEA), an adrenal steroid, causes lipid peroxidation in rat liver microsomes and mitochondria and induces hepatocarcinogenesis. It was investigated whether α-tocopherol, a naturally occurring free radical chain terminator, could decrease lipid peroxidation. When DHEA-free diet supplemented with increasing concentrations of α-tocopherol (25, 50, 100, 200, 400 and 1000 mg/kg diet) was fed to rats for 7 days, a marked lipid peroxidation (measured as thiobarbituric acid reactive substances formation) was observed at concentrations 25 and 50 mg/kg in liver microsomes and mitochondria isolated from these animals. Lipid peroxidation was significantly reduced at concentrations ≥ 100 mg/kg. When DHEA (500 mg/kg diet) was fed to rats simultaneously with increasing concentrations of α-tocopherol, strong lipid peroxidation was observed at a-tocopherol concentrations ≤ 200 mg/kg diet. However, microsomes and mitochondria isolated from livers of rats fed a-tocopherol at doses of 400 and 1000 mg/kg diet produced only negligible amounts of thiobarbituric acid reactive substances. The data show that high concentrations of α-tocopherol in the diet decrease DHEA-induced microsomal and mitochondrial lipid peroxidation. Our results support the concept thatα-tocopherol can protect against DHEA-induced lipid peroxidation and consequently against steroid-induced liver cell damage and, perhaps, also tumour development.     

In vivo effects of CB1 receptor ligands on lipid peroxidation and antioxidant defense systems in the rat brain of healthy and ethanol-treated rats

In vivo experiments were conducted to study the effects of N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-cochlo-rophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A; a potent and selective CB(1)-receptor antagonist) and ara-chidonyl-2-chloroethylamide (ACEA; a selective CB(1)-receptor agonist) on spontaneous lipid peroxidation, glutathione (GSH) level and activities of antioxidant enzymes in rat tissues. Single doses of SR141716A(3 mg/kg, ip) and ACEA(10 mg/kg, ip) had no effect on all indices, studied in the brain, except for a decrease in GSH level by 10 mg/kg of SR141716A. The effects of repeated administration of the CB(1)-receptor ligands (3 mg/kg, ip, once daily for 2 days) on the above indices in the brain and liver of control and ethanol-treated animals were also studied. Two weeks after ethanol exposure, the rats lost weight (by 41%), which correlated with their decreased water and food consumption (by 52% and 33%, respectively). The time of ethanol action was not sufficient to change the biochemical parameters in the brain, except for the lipid peroxidation. However, a decrease in GSH level and superoxide dismutase activity, as well as an increase in lipid peroxidation and glucose-6-phosphate dehydrogenase activity were registered in the liver. The repeated administration of CB(1) receptor ligands restored some of ethanol-induced changes. The present results suggested lack of pro-oxidant activity and potential antioxidant ability of the studied CB(1) receptor ligands, which might contribute to their beneficial effects.     

Effect of vanadyl sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin-induced diabetic rats.

Diabetes mellitus is a significant risk factor for cardiovascular complications. Experimental evidence suggests that oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. This study was undertaken to investigate the effect of vanadyl sulfate on blood glucose, serum and tissue lipid profiles and on stomach and spleen tissues in STZ-induced diabetic rats. In this study, male 6-6.5-month-old Swiss albino rats were used. Rats were randomly divided into four groups. Group I: control animals (normal, nondiabetic animals) (n = 13); Group II: vanadyl sulfate controls (n = 5); Group III: streptozotocin (STZ)-diabetic, untreated animals (n = 11); and Group IV: STZ diabetic animals given vanadyl sulfate (n = 11). Experimental diabetes was induced by intraperitoneal (i.p.) injection of STZ in a single dose of 65 mg kg(-1) body weight. Vanadyl sulfate was administered by gavage at a dose of 100 mg kg(-1). The levels of cholesterol, phospholipid, high density lipoprotein-cholesterol (HDL-), low density lipoprotein-cholesterol (LDL-), very low density lipoprotein-cholesterol (VLDL-), triglycerides and lipid peroxidation (LPO) in serum and cholesterol in liver were assayed according to standard procedures. The levels of lipid peroxidation, glutathione (GSH) and nonenzymatic glycosylation (NEG) in stomach and lipid peroxidation and glutathione (GSH) in spleen tissues were analyzed. After 60 days of treatment, serum cholesterol, LDL-cholesterol, triglyceride, phospholipid, VLDL-cholesterol, LPO, blood glucose levels, stomach LPO and NEG, spleen LPO significantly increased, but serum HDL-cholesterol, stomach GSH and spleen GSH levels significantly decreased in the diabetic group. On the other hand, treatment with vanadyl sulfate reversed these effects. These results reveal that diabetes mellitus increased oxidative damage in stomach and spleen tissues and vanadyl sulfate has an ameliorating effect on the oxidative stress via its antioxidant property. The administration of vanadyl sulfate may be able to reduce hyperglycemia and hyperlipidemia related to the risk of diabetes mellitus.     

Heme oxygenase is the main protective enzyme in rat liver upon 6-day administration of cobalt chloride

Changes in the activities of rat liver heme oxygenase (HO), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), as well as changes in lipid peroxidation and reduced glutathione (GSH) levels were measured after acute loading and chronic administration of cobalt chloride (CoCl2). Acute loading was achieved by a single subcutaneous injection of 60 mg CoCl2/kg body weight for 24 h. Chronic administration was performed by giving the same total amount of CoCl2 in small doses over longer periods of time: 30 mg CoCl2/kg daily for 2 days, 15 mg CoCl2/kg daily for 4 days, or 10 mg CoCl2/kg daily for 6 days. The results showed that HO activity was increased both after acute loading (7-fold increase) and upon 6-day administration of CoCl2 (5-fold increase). The GSH level, 24 h after a single injection of CoCl2, was lower than that of the control animals. However, upon chronic administration of small doses CoCl2, the level of GSH increased and was accompanied by an increase in GR activity. Chronic administration of CoCl2 produced persistent oxidative stress, which was illustrated with a continuous increase in lipid peroxidation. At the same time, under these conditions, the activities of oxidative-stress-protective enzymes were either inhibited (SOD, catalase) or not significantly changed (GPx). Collectively, these findings suggest that the sustained up-regulation of HO activity in rat liver upon 6 day administration of CoCl2 would be beneficial by providing the cells with antioxidants, biliverdin and bilirubin, and together with the increased levels of GSH would act as a part of the defence mechanisms against the cobalt-induced oxidative stress.     

EUK-8 and EUK-134 reduce serum glucose and lipids and ameliorate streptozotocin-induced oxidative damage in the pancreas, liver, kidneys, and brain tissues of diabetic rats

In this study, the effects of EUK-8 and EUK-134, as two newly classified antioxidants, on the sera levels of glucose, insulin, lipids, nitric oxide (NO) and also on the extent of lipid peroxidation (measured in term of thiobarbituric acid reactive substances, TBARS), reactive oxygen species (ROS) formation and the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) as well as reduced glutathione (GSH)] in the liver, pancreas, brain and kidneys of streptozotocin (STZ)-induced diabetic rats were evaluated. Results indicated that oral daily administration of EUK-8, EUK-134 (each at 20?mg/kg), and glibenclamide (2.5?mg/kg), as the control drug, to the diabetic rats for 21 consecutive days improved the sera levels of lipids and glucose along with insulin level to varying extents. In addition, treatment of rats with EUK-8, EUK-134, and/or glibenclamide decreased the TBARS, NO, and ROS levels and increased the activities of SOD and CAT as well as the GSH content in various tissues compared to untreated diabetic rats. In conclusion, this study indicated that EUK-8 and Euk-134 compounds improved the antioxidant status by reducing lipid peroxidation and enhancing the antioxidant enzymes activities in various tissues of diabetic rats.     

The influence of manganese on the distribution of essential trace elements. II. The tissue distribution of manganese, magnesium, zinc, iron, and copper in rats after chronic manganese exposure

Two groups of male Sprague-Dawley rats were treated ip for 30 d with either 3.0 mg Mn/kg or an equal volume of 0.9% NaCl. Liver, kidney, pancreas, duodenum, spleen, testes, lungs, brain, skeletal muscle, bone, and blood were analyzed by atomic absorption spectrophotometry for the elements Mn, Mg, Zn, Fe, and Cu. Mn increased in all tissues except liver due to treatment. Bone and pancreas revealed the largest increases. In blood, increased Mn levels were almost totally accounted for by increases in the erythrocyte fraction. Subcellularly, all fractions (crude nuclear, crude mitochondrial, lysosomal, microsomal, and supernatant) revealed elevations in Mn content due to treatment. Mn did not concentrate selectively in any one subcellular fraction. Mn exposure was accompanied by decreased Zn levels in plasma and bone, decreased Mg levels in heart and bone, increased pancreatic Fe concentration, and increased Cu concentrations in plasma and several tissues.     

五味子酚对氧自由基损伤小鼠脾淋巴细胞的保护作用

研究了五味子酚(Sal)对氧自由基损伤小鼠脾淋巴细胞的影响。体外实验结果表明,Sal在5×10^-6mol·L^-1时对Fe²⁺-VitC引起的脾淋巴细胞GSH含量降低有明显的抑制作用,且能阻抑Fe²⁺-Cys引起的MDA生成增加,改善细胞膜的流动性。用扫描电镜观察到Sal在5×10^-4mol·L^-1时可逆转Fe²⁺-VitC引起的脾淋巴细胞表面微绒毛皱折减少、细胞变形等病理改变。体内高氧分压应激损伤小鼠实验表明,igSal20mg·kg^-1×8d可逆转脾淋巴细胞SOD活性代偿性增高,并提高脾淋巴细胞内GSH含量。以上结果提示Sal对氧自由基损伤脾淋巴细胞有保护作用。     

Protective effect of Aquilegia vulgaris L. on aflatoxin B(1)-induced hepatic damage in rats

The aim of the study was to investigate the effect of ethanol and ethyl acetate extract obtained from Aquilegia vulgaris L. on microsomal lipid peroxidation, reduced glutathione level and antioxidant enzymes activity in the liver of rats intoxicated with aflatoxin B(1) (AFB(1)). Animals were pretreated with 12 daily p.o. doses of the extracts tested (100mg/kg body weight). Then AFB(1) was administered intraperitoneally at a single dose of 1.5mg/kg b.w. to evoke the liver damage. α-Tocopherol was used as a positive control. Reduced glutathione (GSH) was depleted in aflatoxin-treated rats by 80% in comparison with that in the controls. The extracts restored the GSH concentration up to the basal level. Microsomal lipid peroxidation stimulated by Fe(2+)/ascorbate (assessed by measuring TBARS) was enhanced in AFB(1)-treated rats by 28% as compared to that in the control group. The extracts caused a decrease in TBARS level by 40% and 27%. Only two antioxidant enzymes were affected by AFB(1) administration. The activity of catalase was reduced by 24% and the activity of glutathione-S-transferase (GST) was increased by 33%. The pretreatment with ethyl acetate and ethanol extract reduced the GST activity by 76% and 30%, respectively. No significant changes in the activity of other antioxidant enzymes were observed in rats treated with the extracts and AFB(1). It can be concluded that multiple pretreatment with the extracts obtained from A. vulgaris attenuated aflatoxin B(1)-induced hepatic damage as evidenced by inhibition of lipid peroxidation and preventing reduced glutathione depletion.     

Anti-stress effects of dehydroepiandrosterone: protection of rats against repeated immobilization stress-induced weight loss, glucocorticoid receptor production, and lipid peroxidation

In the present study, we have (i) examined the biological effects of repeated immobilization stress, and (ii) tested the hypothesis that the adrenal steroid hormone dehydroepiandrosterone (DHEA) is an anti-stress hormone, using male Sprague-Dawley rats. Rats (N = 6) were divided into the following four groups: (i) control, (ii) repeated immobilization stress (2 hr daily, for 60 days), (iii) repeated immobilization stress (2 hr daily, for 60 days) plus daily i.p. administration of 5 mg DHEA/0.1 mL DMSO, and (i.v.) daily i.p. administration of 5 mg DHEA/0.1 mL DMSO alone. Results obtained showed that repeated immobilization stress resulted in a significant (25%) inhibition in body weight gain, a significant increase in adrenal weight, an increase in glucocorticoid receptor (GR) in the liver, thymus, and spleen, decreased plasma triglyceride levels, and increased lipid peroxidation in the liver and heart as compared with control unstressed animals. Interestingly, DHEA administration resulted in a significant reversal in stress-induced inhibition in body weight gain, adrenal weight, GR levels in liver, thymus, and spleen, and lipid peroxidation levels in the liver and heart. In addition, animals treated with DHEA alone without stress showed a significant (15%) inhibition in body weight gain and an almost 60% decrease in plasma triglyceride levels as compared with control unstressed animals. It is concluded that DHEA acts as an anti-stress hormone in rats, as shown in its antagonizing the effects of repeated immobilization stress on total body weight, adrenal weight, GR levels, and free radical generation.     

Curcumin pretreatment protects against acute acrylonitrile-induced oxidative damage in rats

Acrylonitrile (AN) is widely used in the manufacturing of fibers, plastics and pharmaceuticals. Free radical-mediated lipid peroxidation is implicated in the toxicity of AN. The present study was designed to examine the ability of curcumin, a natural polyphenolic compound, to attenuate acute AN-induced lipid peroxidation in the brain and liver of rats. Male Sprague–Dawley rats were orally administered curcumin at doses of 0 (olive oil control), 50 or 100 mg/kg bodyweight daily for 7 consecutive days. Two hours after the last dose of curcumin, rats received an intraperitoneal injection of 50 mg AN/kg bodyweight. Acute exposure to AN significantly increased the generation of lipid peroxidation products, reflected by high levels of malondialdehyde (MDA) both in the brain and liver. These increases were accompanied by a significant decrease in reduced glutathione (GSH) content and a significant reduction in catalase (CAT) activity in the same tissues. No consistent changes in superoxide dismutase (SOD) activity were observed between the control and AN-treatment groups in both tissues. Pretreatment with curcumin reversed the AN-induced effects, reducing the levels of MDA and enhancing CAT activity and increasing reduced GSH content both in the brain and liver. Furthermore, curcumin effectively prevented AN-induced decrease in cytochrome c oxidase activity in both liver and brain. These results establish that curcumin pretreatment has a beneficial role in mitigating AN-induced oxidative stress both in the brains and livers of exposed rats and these effects are mediated independently of cytochrome P450 2E1 inhibition. Accordingly, curcumin should be considered as a potential safe and effective approach in attenuating the adverse effects produced by AN-related toxicants.     

Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver

This study evaluates whether quercetin (25, 50 and 75 mg/kg body weight) treatment has a protective effect on the pro-oxidant-antioxidant state following chronic ethanol treatment in mice. Pretreatment (quercetin 25, 50 and 75 mg/kg body weight for 15 d+co-treatment of ethanol 18%+quercetin for 15 d and ethanol 18% for the 15 d) increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH) in comparison to the ethanol group. No significant differences from the ethanol group were observed in the group after post-treatment (ethanol 18% for 30 d+quercetin 25, 50 and 75 mg/kg body weight for 15 d) with quercetin. A significant increase in lipid peroxidation (malondialdehyde, MDA) products was observed in liver tissue after administration of ethanol, which was attenuated by pre- and post-treatment with a high dose of quercetin. GSH levels increased and oxidized glutathione (GSSG) levels decreased in groups of ethanol-exposed mice that received quercetin for 15 d prior to ethanol exposure. In conclusion, pre-treatment of quercetin may protect against ethanol-induced oxidative stress by directly quenching lipid peroxides and indirectly by enhancing the production of the endogenous antioxidant GSH. There was no protective effect on post-treatment with quercetin.