Fruit vinegars attenuate cardiac injury via anti-inflammatory and anti-adiposity actions in high-fat diet-induced obese rats

Context: Fruit vinegars (FVs) are used in Mediterranean folk medicine for their hypolipidemic and weight-reducing properties.

Objective: To investigate the preventive effects of three types of FV, commonly available in Algeria, namely prickly pear [Opuntia ficus-indica (L.) Mill (Cectaceae)], pomegranate [Punica granatum L. (Punicaceae)], and apple [Malus domestica Borkh. (Rosaceae)], against obesity-induced cardiomyopathy and its underlying mechanisms.

Materials and methods: Seventy-two male Wistar rats were equally divided into 12 groups. The first group served as normal control (distilled water, 7?mL/kg bw), and the remaining groups were respectively treated with distilled water (7?mL/kg bw), acetic acid (0.5% w/v, 7?mL/kg bw) and vinegars of pomegranate, apple or prickly pear (at doses of 3.5, 7 and 14?mL/kg bw, acetic acid content as mentioned above) along with a high-fat diet (HFD). The effects of the oral administration of FV for 18 weeks on the body and visceral adipose tissue (VAT) weights, plasma inflammatory and cardiac enzymes biomarkers, and in heart tissue were evaluated.

Results: Vinegars treatments significantly (p?Discussion and conclusion: These findings suggest that pomegranate, apple and prickly pear vinegars may prevent HFD-induced obesity and obesity-related cardiac complications, and that this prevention may result from the potent anti-inflammatory and anti-adiposity properties of these vinegars.     

Dietary fats modulate methylmercury-mediated systemic oxidative stress and oxidative DNA damage in rats.

We examined the effects of dietary fats on methylmercury (MeHg)-induced systemic oxidative stress and oxidative DNA damage in liver and kidney of male Sprague-Dawley rats. Rats were treated with a casein-based purified isocaloric diet containing 15% by weight soy oil, docosahexaenoic acid (DHA), seal oil, fish oil, or lard for 28 days, and then gavaged with 0, 1, or 3 mg MeHg/kg BW/day for 14 days. Urine was analyzed for 8-hydroxydeoxyguanosine (8-OHdG) and isoprostane, and serum for total antioxidant capacity (TAC). Liver and kidney were analyzed immunohistochemically for 8-OHdG. Both diet and MeHg showed significant main effects on some of these markers. As compared with the vehicle control, 3 mg MeHg/kg BW significantly increased urinary 8-OHdG in the lard group, urinary isoprostane in the DHA, seal oil, and fish oil groups, while significantly decreasing serum TAC in the lard and fish oil groups. In all dietary groups, 8-OHdG positive staining was located mainly in the nuclei of various cell types in liver and kidney. MeHg expressed a significant main increasing effect on 8-OHdG-positive cells in kidney. These results suggest that both dietary fats and MeHg are important mediators of systemic oxidative stress and oxidative DNA damage.     

Effect of Pelargonium reniforme roots on alcohol-induced liver damage and oxidative stress

Context:?Ethnobotanical surveys conducted on Pelargonium reniforme Curtis (Geraniaceae) have shown that the aqueous root extracts are used to treat alcohol-induced liver damage.

Objective:?We evaluated the antioxidant properties of the extract and its effects on alcohol-induced hepatotoxicity using Wistar rats.

Materials and methods:?Alcohol-induced hepatotoxicity studies were carried out by observing the effect of the aqueous root extract on some liver marker enzymes, bilirubin, and total protein after liver damage. The levels of some phenolic compounds were determined by standard methods. Also, the reducing power of the plant extract and its ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH*) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS*⁺) radicals were determined to evaluate its antioxidant activity.

Results and discussion:?The results obtained show that the plant extract possessed significant antioxidant activity. It had a significant level of phenolic compounds, scavenged DPPH* and ABTS*⁺ radicals effectively, and demonstrated good reducing power. This may indicate that the plant contained compounds which can remove toxic metabolites following alcohol abuse. Serum analysis of animals treated with only ethanol showed a significant increase in the levels of liver marker enzymes and total and unconjugated bilirubin, while a significant decrease was observed in the levels of conjugated bilirubin and total proteins. Administration of the plant extract restored the levels of these markers to normal levels, and this indicates the ability of the plant extract to restore normal functioning of a damaged liver.

Conclusion:?The study shows that P. reniforme is a potential source of antioxidants and compounds which are useful in treating alcoholic liver damage.     

褪黑素拮抗肝氧化性损伤的研究进展

近来发现松果腺分泌的褪黑素是一种比维生素Ｅ更有效的自由基清除剂和抗氧化剂。褪黑素具有无毒、易穿透生理解剖屏障和进入亚细胞成分的特点。它可通过供电子直接灭活毒性自由基,并明显增强机体抗氧化防御系统。实验证明,褪黑素能拮抗致癌剂黄樟精、百草枯和脂多糖所致的氧化性肝损伤,有效地保护细胞核ＤＮＡ和脂质膜免受氧化性损伤,刺激谷胱甘肽过氧化物酶和谷胱甘肽还原酶等机体重要的抗氧化酶活性。此外,还发现褪黑素可在促进大鼠切除肝脏再生的同时,影响淋巴细胞亚群分布,调节肝脏药物代谢酶和防止胸腺细胞凋亡。这些研究结果提示,褪黑素的神经免疫调节作用也可能有利于机体抵抗氧化性肝损伤。     

非酒精性脂肪性肝病与氧化应激

非酒精性脂肪性肝病常与肥胖、2型糖尿病和高血压等代谢综合征并存,其与氧化应激的关系越来越受到关注.本文综述非酒精性脂肪性肝病的发病机制、氧化应激及其相关抗氧化剂的研究.     

银杏叶提取物对糖尿病大鼠抗氧化能力的影响

目的研究银杏提取物对糖尿病大鼠的抗氧化能力。方法将36只2型糖尿病模型Wistar大鼠按血糖分层随机分为模型对照组、银杏叶提取物高和低剂量(6和3 mg/kg)组,每组各12只。另取12只健康Wistar大鼠作为正常对照。连续给药4周。测定大鼠体质量、心脏/体质量比,血清及心脏丙二醛(MDA)、还原性谷胱甘肽(GSH)、超氧歧化酶(SOD)和糖基化终产物(AGEs)含量,以及血清糖化血红蛋白(HbA1C)。结果与正常对照组相比,模型对照组体质量、血清和心脏GSH、SOD含量显著降低(P<0.01或0.05),而心脏/体质量比、血清HbA1C以及血清和心脏体MDA、AGEs含量显著升高(P<0.01或0.05);与模型对照组相比,银杏叶提取物高和低剂量组大鼠体质量、血清和心脏GSH和SOD含量显著升高(P<0.01或0.05),而心脏/体质量比、血清HbA1C含量以及血清和心脏体MDA、AGEs含量显著降低(P<0.01或0.05)。结论银杏叶提取物可降低糖尿病大鼠的心脏氧化应激反应,此作用可能与银杏叶提取物预防糖尿病心脏病有关。     

Effect of glycine on oxidative stress in rats with alcohol induced liver injury

We studied the effect of administering glycine on tissue lipid peroxidation and enzymic and non-enzymic antioxidants in experimental hepatotoxic Wistar rats. Hepatotoxicity was induced by administering ethanol for 30 days by intragastric intubation. Glycine administered at a dose of 0.6 g kg(-1) body weight for 30 days significantly inhibited the severe oxidative stress as evidenced by the decreased levels of liver and brain thiobarbituric acid reactive substances (TBARS) and hydroperoxides compared to control. The activities of enzymic and non-enzymic antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in the liver and brain were significantly elevated on glycine supplementation as compared to the untreated alcohol fed rats. The levels of serum vitamin E and vitamin C were also increased to near normal levels on glycine treatment. Microscopic examination of alcohol treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol treated rat brain demonstrated oedma, which was significantly lowered on treatment with glycine. Thus our study shows that administering glycine to alcohol supplemented rats, markedly reduced the oxidative stress and elevated the enzymic and non-enzymic antioxidants in the liver and brain, which a was associated with a reversal of hepatic steatosis and cerebral oedma.     

褪黑素对四氯化碳小鼠肝损伤的保护作用

目的　探讨褪黑素对四氯化碳肝毒性的保护作用。方法　给予小鼠四氯化碳（５ ｍｌ·ｋｇ － １ ） ,继后每隔６ ｈ ｉｐ 褪黑素１０ ｍ ｇ·ｋｇ － １ 。用胶原酶消化法分离小鼠肝细胞后,依次加用褪黑素（１０ － ５ ～１０ － １ １ ｍｏｌ· Ｌ－ １ ） 和四氯化碳（２０ ｍ ｍ ｏｌ· Ｌ－ １ ） 。以测定丙氨酸氨基转换酶（ Ａ Ｌ Ｔ） ,丙二醛（ Ｍ Ｄ Ａ） 和谷胱甘肽过氧化物酶活力,作为四氯化碳肝损伤的指标。用 Ｍ Ｔ Ｔ 法检测肝细胞活力。结果　四氯化碳可使小鼠血液 Ａ Ｌ Ｔ 活性和肝 Ｍ Ｄ Ａ 含量明显上升。体内应用 Ｍ Ｔ １０ ｍ ｇ·ｋｇ － １ ,则明显降低肝匀浆 Ｍ Ｄ Ａ 含量（ Ｐ＜ ００１） , 对血浆 Ａ Ｌ Ｔ 活性无明显影响。体外应用 Ｍ Ｔ（１０ － ５ ～１０ － ７ ｍｏｌ· Ｌ－ １ ） 亦可使肝细胞 Ｍ Ｄ Ａ 含量下降（ Ｐ＜ ００５） ,同时还可使肝细胞 Ａ Ｌ Ｔ 释放率下降,细胞活力上升（ Ｐ＜ ００５） 。结论　 Ｍ Ｔ 拮抗 Ｃ Ｃｌ４ 肝毒性的作用可能与其抗氧化能力有关     

Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepatotoxicity

The present study was designed to evaluate the effect of rutin (RT) on lead (Pb)-induced oxidative stress. Rats were divided into groups and were treated with RT with or without lead. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were evaluated. Levels of AST, ALT, TNF-α, IL-6, and IL-1β were significantly decreased, and the activities of antioxidant enzymes were increased in the liver of rats treated with RT along with Pb. Histologic changes were improved to almost a normal hepatic structure. The results suggest that RT controls the damaged antioxidant status in Pb-induced oxidative stress.     

Antilithiatic effect of aqueous and ethanolic extracts of cactus prickly pear in chemically induced urolithiasis in rats

This study investigated the antiurolithiasic effects of the aqueous and ethanolic extracts of cactus prickly pear fruit in male Wistar rats. The effect of oral administration of cactus fruit extracts were studied on calcium oxalate urolithiasis. Forty-two rats were used for the study. The animals were divided into seven groups of six animals each. Control group maintained on regular rat food and drinking water throughout the study period, whereas in other groups nephrolithiasis was induced by ethylene glycol and ammonium chloride. Rats in kidney stone group were sacrificed after 28?days and all remaining groups after 58?days. Treatment groups were treated with 1?mg/kg and 100?mg/kg of aqueous and ethanolic extracts of Cactus fruit for 30?days. Urinary calcium level was decreased significantly by ethanolic extracts of cactus fruit and urinary creatinine, magnesium and citrate levels were increased significantly by aqueous and ethanolic extracts of cactus fruit dose dependently. Serum phosphorus level was decreased significantly in treatment groups dose dependently and serum creatinine, urea and uric acid levels were found to be similar as in control group.     

Hepatoprotective effects of Tagetes lucida root extract in carbon tetrachloride-induced hepatotoxicity in Wistar albino rats through amelioration of oxidative stress

ContextThe roots of Tagetes lucida Cav. (Asteraceae) have antioxidant and antimicrobial properties.ObjectiveThis study aimed to examine the hepatoprotective effects of T. lucida roots ethanol extract (TLRE) using carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats.Materials and methodsThe active ingredients of TLRE were identified by high-performance liquid chromatography, infra-red spectrum, and mass spectrometric procedures. Ninety rats were distributed into four main groups: positive, therapeutic, protective, and negative group. The therapeutic group was implemented using CCl₄ (a single dose of 2 mL/kg) before TLRE or silymarin administration. Meanwhile, the protective group was implemented by administering CCl₄ (a single dose of 2 mL/kg) after force-feeding TLRE or silymarin. Each therapeutic and protective group was divided into three subgroups: force-fed with saline, TLRE (500 mg/kg), and silymarin (25 mg/kg). The positive group was split into two subgroups that were force-fed TLRE and silymarin. Positive, therapeutic, and protective groups were compared to the negative group (untreated rats). CCl_4, TLRE, and silymarin were orally administrated using a gastric tube.ResultsIn the therapeutic and protective groups, TLRE significantly reduced liver enzymes, i.e., aspartate aminotransferase (12.47 and 6.29%), alanine aminotransferase (30.48 and 11.39%), alkaline phosphatase (17.28 and 15.90%), and cytochrome P450-2E1 (39.04 and 48.24%), and tumour necrosis factor-α (53.72 and 53.72%) in comparison with CCl₄-induced hepatotoxicity controls.ConclusionsTLRE has a potent hepatoprotective effect with a good safety margin. After a repeated study on another type of small experimental animal, their offspring, and an experiment with a large animal, this study may lead to clinical trials.     

Induction of oxidative stress in liver and kidney of rats exposed to Nigerian bonny light crude oil

The local population of Niger‐Delta in the Southern part of Nigeria have used bonny light crude oil (BLCO) as a remedy for various ailments and are exposed to some extent to this widespread environmental contaminant or its metabolites through the food chain. BLCO's hepatorenal toxicity was studied using oxidative stress indices to elucidate the precise nature and mechanism of action. BLCO was orally administered at concentrations of 0, 200, 400, and 800 mg kg^?1 to adult male rats for 7 days. After exposure, kidney weight was unaffected, but liver weight decreased significantly at 800 mg kg^?1 only compared with control. BLCO exposure resulted in dose‐dependent elevation of serum aminotransferases, total bilirubin, urea, and creatinine. Activities of superoxide dismutase and catalase decreased significantly, whereas γ‐glutamyltransferase activity and the level of glutathione increased significantly in BLCO‐treated animals compared with control in both liver and kidney of rat. Renal activities of glucose‐6‐phosphatase and 5′‐nucleotidase markedly decreased in a dose‐dependent manner in BLCO‐exposed rats. In addition, the levels of hydrogen peroxide and lipid peroxidation significantly increased, dose dependently, in liver and kidney of BLCO‐treated rats compared with control. BLCO‐treated rats showed marked degeneration of kidney evident in cortical hemorrhages, tubular necrosis, protein casts, and cellular infiltration. However, no treatment‐related liver histopathology was observed. The results suggested that BLCO elicits disruption of antioxidant status and concomitant elevation of hydrogen peroxide and lipid peroxidation differentially in liver and kidney of rats. The hepatorenal toxicity of BLCO could be due to induction of oxidative stress in liver and kidney. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.     

Heart and kidney oxidative stress status in septic rats treated with caraway extracts

Context:?Carum carvi L., (Umbelliferae) known as caraway, is a famous traditional herbal plant supposed to contain active components with pharmacological properties.

Objective:?In this study, the effects of caraway extracts on preventing sepsis induced by oxidative tissue injuries have been investigated by measuring heart and kidney oxidative stress parameters.

Materials and methods:?Sepsis was induced in rats (n?=?6) by experimental cecal ligation and puncture (CLP) model. Then, either hydroalcoholic extract or essential oils (50 and 100?mg/kg body weight) were injected intraperitonially immediately after CLP operation. Twenty-four hours after CLP, the rats were anesthetized when kidney and heart tissues were removed to analyze the tissue oxidative stress parameters, that is, glutathione (GSH) and lipid peroxidation (LP).

Results:?Sepsis induction caused a significant increase in kidney but not heart LP, indicating that kidney was more affected by sepsis induction than heart. Kidney LP and plasma urea/creatinine ratio levels were readily reversed in rats treated with essential oils but not in those treated with hydroalcoholic extract. Unlike LP, the heart and kidney GSH levels were not affected in all treated groups.

Discussion and conclusion:?Our data imply that caraway oils probably have a protective role in kidney tissue against oxidative injury in advanced stages of sepsis.     

Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity

We have evaluated the effect of gentamicin and gentamicin plus quercetin on ROS production, endogenous antioxidant defenses (SOD and CAT) and lipid peroxidation in vitro on human leukocytes and in vivo on whole rat blood. Gentamicin generated ROS production in human leukocytes, produced a dual effect on both enzymes dosage-dependent and generated an increase in lipid peroxidation. Quercetin, in leukocytes stimulated by gentamicin, showed more inhibitory capacity in ROS production than the reference inhibitor (vitamin C) in mononuclear cells and a similar protective behavior at this inhibitor in polymorphonuclear cells. Quercetin, in both cellular systems, tend to level SOD and CAT activities, reaching basal values and could prevent lipidic peroxidation induced by gentamicin. The results in Wistar rats confirmed that therapeutic doses of gentamicin can induce oxidative stress in whole blood and that the gentamicin treatment plus quercetin can suppress ROS generation, collaborate with SOD and CAT and diminish lipid peroxidation. Finally, flavonoid and antibiotic association was evaluated on the antimicrobial activity in S. aureus and E. coli, showing that changes were not generated in the antibacterial activity of gentamicin against E. coli strains, while for strains of S. aureus a beneficial effect observes. Therefore, we have demonstrated that gentamicin could induce oxidative stress in human leukocytes and in whole blood of Wistar rats at therapeutic doses and that quercetin may to produce a protective effect on this oxidative stress generated without substantially modifying the antibacterial activity of gentamicin against E. coli strains, and it contributes to this activity against S. aureus strains.     

Effect of Spirulina platensis ingestion on the abnormal biochemical and oxidative stress parameters in the pancreas and liver of alloxan-induced diabetic rats

Context: Previous studies have shown that Spirulina platensis Gomont (Phormidiaceae) (SP) extract has beneficial effects on many disease conditions. The putative protective effects of SP were investigated in diabetic rats.

Objective: The current study investigates the antioxidant effects of SP in diabetic Wistar rats.

Materials and methods: Alloxan monohydrate (150?mg/kg body weight) was intraperitoneally administrated to induce diabetes. An aqueous suspension of SP powder in distillate water (10% w/v) was administrated orally by gavage (1?mL/day) for 50?days. Histopathological, biochemical and antioxidant analyses were performed. Glycemia, liver function and HOMA-IR were assessed using Spinreact and ELISA kits.

Results: SP exhibited high-antioxidant activity. The IC₅₀ values of the SP aqueous extract were 70.40 and 45.69?mg/L compared to those of the standard antioxidant BHT, which were 27.97 and 19.77?mg/L, for the DPPH and ABTS tests, respectively. The diabetic animals showed a significant increase in glycaemia (from 4.05 to 4.28?g/L) and thiobarbituric acid reactive substances (50.17?mmol/g protein) levels. Treatment with SP significantly reduced glycaemia by 79% and liver function markers [glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT) and alkaline phosphatase (Alk-p)]) by 25, 36 and 20%, respectively, compared to that of the controls. There was a significant increase in superoxide dismutase (48%), total antioxidant status (43%), glutathione peroxidase (37%) and glutathione reductase (16%) in the diabetic rats treated with SP.

Discussion and conclusion: These results showed that SP has high antioxidant activity, free radical scavenging, antihyperglycemic and hepatoprotective effects in diabetes.     

Preparation method and stability of ellagic acid-rich pomegranate fruit peel extract

A simple one-step purification using liquid–liquid extraction for preparing pomegranate peel extract rich in ellagic acid has been demonstrated. The method involved partitioning of the 10% v/v water in methanol extract of pomegranate peel between ethyl acetate and 2% aqueous acetic acid. This method was capable of increasing the ellagic acid content of the extract from 7.06% to 13.63% w/w. Moreover, the antioxidant activity of the extract evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay was also increased (ED₅₀ from 38.21 to 14.91?μg/mL). Stability evaluations of the ellagic acid-rich pomegranate peel extract in several conditions through a period of four months found that the extracts were stable either kept under light or protected from light. The extracts were also stable under 4° ± 2°C, 30° ± 2°C and accelerated conditions at 45°C with 75% relative humidity. However, study on the effect of pH on stability of the extract in the form of solution revealed that the extract was not stable in all tested pH (5.5, 7 and 8). These results indicated that the ellagic acid-rich pomegranate peel extract was stable when it was kept as dried powder, but it was not stable in any aqueous solution.     

Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats

Context: In the absence of reliable liver-protective drugs in modern medicine, a large number of medicinal preparations are recommended for treatment of liver disorders.

Objective: The antioxidant, hepatoprotective and kidney protective activities of methanol extracts of Ficus carica Linn. (Moraceae) leaves and fruits and Morus alba Linn. root barks (Moraceae) are evaluated here.

Materials and methods: Liver and kidney damage were induced in rats by carbon tetrachloride in a subcutaneous dose of 1?mL (40% v/v in corn oil)/kg. The extract was given intraperitoneally at doses of 50?mg/kg (F. carica leaf and M. alba root bark) and 150?mg/kg (F. carica fruit). The activity of the extracts was comparable to that of silymarin, a known hepatoprotective agent. Antioxidant activity was evaluated by measuring blood glutathione (GSH) content, superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde equivalent (MDA). Hepatoprotective activity was evaluated by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein. These biochemical observations were supported by histopathological examination of liver sections. Kidney function was evaluated by measuring plasma urea and creatinine.

Results: Methanol extracts of Ficus carica and Morus alba showed potent antioxidant and hepatoprotective activities; in-depth chromatographic investigation of the most active extract (Ficus carica leaf extract) resulted in identification of umbelliferone, caffeic acid, quercetin-3-O-β-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside.

Discussion and conclusion: These findings demonstrate that the phenolic constituents of Ficus carica leaf and Morus alba root bark are responsible at least in part for the observed protective effects.     

Safrole-induced oxidative damage in the liver of Sprague-Dawley rats.

Safrole is a weak hepatocarcinogen, and its carcinogenic effect has been linked to the formation of stable safrole DNA adducts. In this study, we tested whether safrole also induces oxidative damages in Sprague-Dawley rats. By single i.p. injection, safrole dose-dependently induced the formation of hepatic lipid hydroperoxides (LHP) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The safrole-induced LHP reached peak level on day 3 and gradually returned to the basal level on day 15. On the other hand, 8-OH-dG levels from the similarly treated rats peaked on day 5 and returned to basal level on day 15. Safrole also dose-dependently induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. We also examined the protective effect of vitamin E, deferoxamine and N-acetylcysteine against the safrole-induced oxidative damage. N-Acetylcysteine, the precursor of glutathione, exerted the greatest protective effect among the three antioxidants tested. In contrast, buthionine sulfoximine, the glutathione synthesis inhibitor, enhanced the safrole-induced oxidative damage, as evidenced by the elevation of LHP and 8-OH-dG levels on day 3 (P<0.05). These findings demonstrate that safrole treatment induces oxidative damage in rat hepatic tissue, and glutathione plays an important protective role. This oxidative damage may be involved in the hepatocarcinogenic effect of safrole.     

Enzymatic studies of cisplatin induced oxidative stress in hepatic tissue of rats

Cisplatin is an active cytotoxic agent that has proved to be successful in the treatment of various types of solid tumors. The drug-induced nephrotoxicity has been very well documented in clinical oncology. However, hepatotoxicity has been rarely characterized and paid attention to, and is the least studied. We have used rat as the model to evaluate the effect of cisplatin on liver antioxidant enzymes and to determine whether these modulations in enzymatic activities are involved in hepatotoxicity. Reports obtained from our study indicate that cisplatin increases lipid peroxidation in the treated tissue of rat. The drug is also involved in altering the thiol status of the tissue with concomitant alterations in the enzymatic antioxidants. Glutathione and glutathione reductase levels were significantly decreased after cisplatin therapy, whereas glutathione peroxidase, gamma-glutamyl transpeptidase and catalase showed a significant increase. No statistically significant change was observed in glutathione-S-transferase activity. After cisplatin treatment, cytochrome P 450 showed a significant increase, whereas cytochrome b5 was decreased. Thus, an alteration in enzymatic antioxidant status with increase in lipid peroxidation indicates that the enzymes play an important role in combating free radical induced oxidative stress on the tissue.     

锌7-金属硫蛋白对严重烫伤大鼠肝脏氧化应激反应的作用

AIM: Using the model of burned animal with delayed resuscitation to study antagonistic effect of Zn7 - metallothionein(Zn7-MT) on oxidative stress in the liver of rats suffered from severe thermal injury on skin. METHODS: Tocompare the changes in antioxidant concentrations and antioxidative enzyme activities in the liver or plasma ofburned rats with or without Zn7-MT in resuscitation fluid by biochemical assay. RESULTS: After injury, glutathione concentration was progressively decreased with time, At24 h after injury, activities of glutathione reductase and glutathione peroxidase in the liver of burned rats were increased and then decreased at 48 h postburn, αTocopherol in plasma was reduced at 24 h and malondialdehyde in the liver was increased significantly postburn.MT and MT-1 mRNA expression in burned rats were activated. Taken together, oxidative stress in the liver ofburned rats occurred. Exogenous Zn7-MT attenuated the changes in antioxidant concentrations and antioxidativeenzyme activities in the liver or plasma of burned rats. The effect of Zn7-MT was in a concentration-dependentmanner and the concentration of 10μtmol/L was the most effective. Exogenous Zn7-MT also inhibited MT-1 mRNA overexpression and increased MT protein concentration. CONCLUSION: Zn7-MT effectively antagonizedoxidative stress in the liver of rats with severe thermal injury.