Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats

Oxidative stress plays an important role in chronic complications of diabetes. In the present study the antioxidant effect of oral administration of ethanolic extract of Eugenia jambolana seed kernel on tissue antioxidant enzymes and lipid peroxidation in liver and kidney of streptozotocin-induced diabetic rats was evaluated. Administration of seed kernel to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased body weight gain, plasma insulin and hemoglobin. The diabetic rats showed the low activities of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione content in liver and kidney, which were restored to near normal levels by treatment with the seed kernel extract. The increased levels of lipid peroxidation and hydroperoxides in diabetic rats were reverted back to near normal levels after the treatment with seed kernel extract. Diabetic rats treated with seed kernel extract restored almost normal architecture of liver and kidney and were confirmed by histopathological examination. The present study reveals the efficacy of Eugenia jambolana seed kernel in the amelioration of diabetes, which may be attributed to its hypoglycemic property along with its antioxidant potential. The antioxidant effect of Eugenia jambolana seed kernel was also compared with glibenclamide, a standard hypoglycemic drug.     

Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats

In the present study, an attempt has been made to evaluate the presence of antioxidant property in the alcoholic extract of Aloe vera leaf gel. Oral administration of Aloe vera gel extract at a concentration of 300 mg/kg to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased hemoglobin. The increased levels of lipid peroxidation and hydroperoxides in tissues of diabetic rats were reverted back to near normal levels after the treatment with gel extract. The extract treatment also resulted in a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver and kidney of diabetic rats. These results clearly show the antioxidant property of Aloe vera gel extract. The extract was also more effective than glibenclamide in restoring the values of these parameters.     

Yacon roots (Smallanthus sonchifolius) improve oxidative stress in diabetic rats

Abstract

Context: Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae (yacon) roots are a natural product recognized by the traditional medicine to treat diabetes-related problems. There are no reports concerning the potential of yacon roots to reduce oxidative stress and ameliorate diabetes complications in diabetic animals.

Objective: This work analyzes the in vivo antioxidant activity and beneficial effects of yacon roots, using a model of streptozotocin-induced diabetes in rats.

Materials and methods: Lipid peroxidation and other indicators of oxidative stress were determined in liver and kidney homogenates from non-diabetic rats, untreated diabetic rats, and diabetic rats treated orally with yacon flour (340?mg fructooligosaccharide/kg/d) as a diet supplement for 90?d. Biochemical parameters were determined in liver, kidney, and blood at the end of the experimental period.

Results: Yacon supplementation to diabetic rats produced a significant decrease in malondialdehyde levels in both liver (?30.97%) and kidney (?19.15%). Hepatic superoxide dismutase and catalase activities were significantly lower in diabetic-treated rats (?13.46 and ?64.33%, respectively) compared with diabetic controls. Similar results were observed in kidney. The treatment of diabetic rats produced an increase of glutathione peroxidase and glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78 and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and liver fatty acid composition, which were altered in diabetic rats, reverted back to nearly normal with yacon treatment.

Conclusions: These results indicate that yacon root flour is a potential diet supplement with high in vivo antioxidant activity.     

Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats

The effect of a herbomineral formulation (HMF) on early diabetic nephropathy was investigated. Diabetes was induced in Wistar rats by administering streptozotocin (55 mg/kg, intraperitoneally). The occurrence of early diabetic nephropathy in rats was revealed by high plasma glucose and depleted liver glycogen, decreased glucose uptake by peripheral tissue, impaired renal function, increased antioxidants and lipid peroxidation in kidney. These changes were accompanied by elevated malondialdehyde, glutathione and superoxide dismutase activity in kidney. Furthermore, increased total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio, increased relative kidney weight, decreased glomerular filtration rate (GFR) and urinary creatinine were also observed in diabetic nephropathy rats. HMF treatment significantly lowered blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen, triglycerides, total cholesterol, serum albumin level, total urine volume, urinary albumin excretion rate, urinary albumin to creatinine ratio and relative kidney weight, and increased urinary creatinine and GFR. Altered levels of antioxidants, viz. lipid peroxidation, glutathione and superoxide dismutase (SOD), in kidney of diabetic nephropathy rats were restored. Histopathological findings indicated dense mesangial matrix in the glomeruli of diabetic nephropathy rats, which may be due to over-activation of matrix metalloproteinases and was reduced following HMF treatment. Our experimental findings clearly demonstrate that HMF has an ability to prevent the progression of early diabetic nephropathy. Such protective effect of HMF might be due to the presence of flavonoids (catechin, quercetin, rutin) and triterpene saponins (oleanolic acid and gymnemic acid) which are known to possess potent antioxidant properties.     

Effect of aqueous Enicostemma littorale Blume extract on key carbohydrate metabolic enzymes, lipid peroxides and antioxidants in alloxan-induced diabetic rats

The present study investigates the effect of oral administration of an aqueous Enicostemma littorale whole plant extract on some key carbohydrate metabolic enzymes and antioxidant defence in alloxan-induced diabetes in rats. Rats were rendered diabetic by alloxan (150 mgkg(-1) body weight) administration. Oral administration of E. littorale extract for 45 days increased the activity of hexokinase and decreased the activities of glucose 6-phosphatase and fructose 1,6-bisphosphatase significantly in the serum, liver and kidney of diabetic rats. The extract lowered the concentration of thiobarbituric acid reactive substances and lipid hydroperoxides significantly in brain and increased it significantly in heart in diabetic rats. E. littorale administration increased the concentration of reduced glutathione and the activity of glutathione peroxidase in diabetic rats. The activities of superoxide dismutase and catalase were increased significantly by E. littorale treatment in diabetic rats. The effect of a 2 g kg(-1) dose was greater than that of a 1 gkg(-1) dose. Insulin (6 units kg(-1)) normalized all the parameters in diabetic rats. Our study has provided evidence for the antidiabetic activity of E. littorale aqueous extract. This study can also be extrapolated to clinical studies in future.     

Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats.

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus.     

Fungal metabolite nigerloxin ameliorates diabetic nephropathy and gentamicin-induced renal oxidative stress in experimental rats

Elevated polyol pathway enzyme activities and oxidative stress play an important role in the development and progression of diabetic nephropathy. Here, we investigated the beneficial influence of nigerloxin, a fungal metabolite and a potent aldose reductase inhibitor and free radical scavenger in the kidney of streptozotocin-induced diabetic rats. A group of diabetic rats was orally administered with nigerloxin for 30 days (100 mg/kg). Diabetic rats showed increased lipid peroxides, advanced glycation end products (AGEs), elevated activities of polyol pathway enzymes, and lowered antioxidant defense system in kidney. Administration of nigerloxin decreased kidney lipid peroxides and AGEs. Activities of polyol pathway enzymes were reduced while activities of all antioxidant enzymes, glutathione, and ascorbic acid were elevated in the kidney of nigerloxin-treated diabetic rats. We also investigated antioxidant potential of nigerloxin in gentamicin-induced nephrotoxicity in Wistar rats. Groups of rats were orally administered with nigerloxin for 8 days (25 mg or 100 mg kg^?1 body weight day^?1) along with gentamicin (80 mg/kg, i.p., for 8 days). Gentamicin induced increase in lipid peroxides, decrease in glutathione and activities of antioxidant enzymes in the kidney, and increase in blood creatinine, and urea concentrations were significantly countered by nigerloxin treatment. Thus, the results indicated the beneficial influence of nigerloxin on polyol pathway and oxidative stress associated with diabetes, which are implicated in ameliorating the development of diabetic nephropathy. Nigerloxin also ameliorated oxidative stress induced by gentamicin in the renal tissue.     

姜黄素固体分散体对2型糖尿病大鼠氧化应激的影响

目的研究姜黄素固体分散体对2型糖尿病大鼠氧化应激的影响。方法以聚乙烯吡咯烷酮（PVP）为载体制备姜黄素固体分散体。大鼠腹腔注射小剂量链脲佐菌素（STZ）建立2型糖尿病模型,随机分成糖尿病模型（MD）组、聚乙烯吡咯烷酮（PVP）组、姜黄素（CU）组、姜黄素固体分散体低剂量（LSD）组、姜黄素固体分散体高剂量（HSD）组。大鼠给药6周后,测定血清及肾脏组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）的活力,丙二醛（MDA）的含量。结果与正常对照组比较,MD组大鼠超氧化物歧化酶、谷胱甘肽过氧化物酶活力显著降低,氧化应激增强;与MD组比较,姜黄素固体分散体组SOD、GSH-Px活力显著提高,MDA含量显著降低。结论姜黄素固体分散体可显著提高糖尿病大鼠的抗氧化能力,抑制氧化应激。     

Antioxidant Effect of Tinospora cordifolia Extract in Alloxan-induced Diabetic Rats

Many plants are claimed to possess antidiabetic and antioxidant activity. In practice, it is being increasingly recognized to be an alternative approach to modern medicine. This study assess the antioxidant capacity of Tinospora cordifolia stem methanol extract in daily oral administration of 500 mg/kg of body weight for 40 days in alloxan induced diabetic rats. The erythrocytes membrane lipid peroxide and catalase activity was increased where as the activities of superoxide dismutase, glutathione peroxidase were found to be decreased significantly (P<0.01) in alloxan-induced diabetic rats. The levels of lipid peroxide in liver of diabetic rats increased significantly (P<0.01) and catalase, superoxide dismutase, glutathione peroxidase in liver was significantly decreased in alloxan-induced diabetic rats, when compared to normal rats. After treatment of methanol Tinospora cordifolia stem extract brings back to normal (P<0.01) in the erythrocytes membrane and liver cell enzymes activities.     

Effect of taurine supplementation on cytochrome P450 2E1 and oxidative stress in the liver and kidneys of rats with streptozotocin-induced diabetes

To investigate whether diabetes-induced alterations of CYP2E1 and oxidative stress can be modulated by dietary taurine supplementation, male Wistar rats were divided into non-diabetic, diabetic, and diabetic taurine-supplemented groups (administered at 2% in the drinking water). Increased levels of CYP2E1-catalyzed p-nitrophenol hydroxylation were found in liver and kidney microsomes of rats with STZ-induced diabetes compared to those of non-diabetic control rats. Immunoblot and RT-PCR analyses of CYP2E1 protein and mRNA levels in the liver and kidneys showed the same trend as with enzyme activities. Taurine supplementation significantly decreased the enzyme activity and expression (protein and mRNA) of CYP2E1 in diabetic rat kidneys. Plasma β-hydroxybutyrate concentration was significantly reduced in taurine-treated diabetic rats. The induction of heme oxygenase-1 mRNA was suppressed by taurine treatment in diabetic rat kidneys. An increase in reduced glutathione (GSH) and a higher ratio of reduced to oxidized glutathione (GSH/GSSG) together with lower values of thiobarbituric acid-reactive substances (TBARS) were observed in the kidneys of taurine-treated diabetic rats. However, taurine supplementation caused only a slight or insignificant effect on these alternations in the liver of diabetic rats. Our results show dietary taurine may reduce CYP2E1 expression and activity, and oxidative stress in kidneys of diabetic rats.     

Antioxidant activity of Albizzia lebbeck (Linn.) Benth. in alloxan diabetic rats

There is an increasing demand for natural anti-diabetic drugs, as continuous oral administration of insulin can culminate in many side effects and toxicity. In our endeavour to formulate some cost-effective herbal medicines for diabetes, we undertook this study to evaluate the antioxidant potential of aqueous extract of Albizzia lebbeck (ALL) in diabetic rats. The oxidative stress in alloxan-induced diabetic rats was determined by estimating the levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and reduced glutathione (GSH) in liver and kidneys. Activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S transferase (GST) were assessed in diabetic as well as rats co-administered with ALL. Oxidative damage in the liver and kidneys of diabetic rats as evidenced by a marked increment in the levels of TBARS and CD, and also a distinct diminution in GSH content was nullified by ALL, as these parameters showed a tendency to retrieve towards normalcy on co-administration of the herbal drug. The antioxidant enzymes registered a decline in activity in diabetic rats thus revealing the damaging effects of free radicals generated due to alloxan exposure. The activities of these enzymes returned to normalcy in ALL-administered rats indicating the antioxidant efficacy of the drug in resisting oxidative insult. The findings provide a rationale for further studies on isolation of active principles and pharmacological evaluation.     

Effect of Terminalia arjuna stem bark on antioxidant status in liver and kidney of alloxan diabetic rats

Free radicals and associated oxidative stress induced by alloxan are implicated in eliciting pathological changes in diabetes mellitus. Terminalia arjuna bark, an indigenous plant used in ayurvedic medicine in India, primarily as a cardiotonic is also used in treating diabetes, anemia, tumors and hypertension. The present study examined the effect of ethanolic extract (250 and 500 mg/kg body weight) of Terminalia arjuna stem bark in alloxan induced diabetic rats and its lipid peroxidation, enzymatic and nonenzymatic activity was investigated in the liver and kidney tissues. The extract produced significant (P<0.05) reduction in lipid peroxidation (LPO). The effect of oral T. arjuna at the dose of 500 mg/kg body weight was more than the 250 mg/kg body weight. The extract also causes a significant (P<0.05) increase in superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase glutathione reductase and glucose-6-phosphate dehydrogenase, reduced glutathione, vitamin A, vitamin C, vitamin E, total sulfhydryl groups (TSH) and non protein sulfhydryl groups (NPSH) in liver and kidney of alloxan induced diabetic rats, which clearly shows, the antioxidant property of T. arjuna bark. The result indicates that the extract exhibit the antioxidant activity through correction of oxidative stress and validates the traditional use of this plant in diabetic animals.     

Flax and Pumpkin seeds mixture ameliorates diabetic nephropathy in rats

This study investigated the hypoglycemic and antioxidant effects of Flax and Pumpkin seeds mixture on the kidney of alloxan-induced diabetic rats. Animals were allocated into three groups of six rats each: a control group (CD), a diabetic group (DD) and diabetic rats fed with Flax and Pumpkin seeds mixture (DMS) group. The DD rats showed a significant increase of glycemia and lipid parameters such as total lipid, total cholesterol and triglycerides levels compared to those of the control group (CD). In addition, plasma and kidney malonaldialdehyde levels (MDA) were significantly increased compared to (CD) group. Antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD) and non-enzymatic levels of reduced glutathione (GSH) significantly decreased in the plasma and kidney of diabetic rats compared to those of controls. Diet supplemented with Flax and Pumpkin seeds mixture ameliorated the antioxidant enzymes activities observed in diabetic rats and significantly decreased MDA levels. Kidney histological sections, showed glomerular hypertrophy and tubular dilatation. In DMS rats, these histopathological changes were less prominent. Our results suggest that Flax and Pumpkin seeds mixture supplemented in diet of diabetic rats may be helpful to prevent diabetes and its complications.     

Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes

Diospyros peregrina is an edible fruit of costal West-Bengal. The present investigation was undertaken to evaluate the role of aqueous extract of D. peregrina fruit in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration of extract at the doses of 50 and 100 mg/kg body weight per day for 28 days to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity. An increased reactive oxygen species and insufficient antioxidant activity is associated with diabetes mellitus, which is mainly responsible for diabetic pathogenesis. The role of extract on antioxidant markers of liver and kidney were estimated. The diabetic rats exhibited 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 level of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxide) in diabetic rats was also found to be reverted back to near normal status in extract treated groups.     

Effect of the sulfonylurea glyburide on glutathione and glutathione peroxidase activity in alloxan-induced diabetic rat hepatocytes

1. The effect of glyburide treatment on glutathione peroxidase activity and glutathione levels of non-insulin diabetic rats has been studied.2. Hepatic glutathione and glutathione peroxidase concentrations were significantly reduced in diabetic animals.3. Glyburide treatment of diabetic rats for 4 weeks corrected the changes on the glutathione levels observed in diabetic liver.4. High blood glucose levels of untreated diabetic rats were decreased following glyburide treatment as well.5. Administration of glyburide to diabetic rats reversed the diabetes-induced changes suggesting that glyburide may directly increase liver glutathione concentrations.     

Enicostemma littorale Blume aqueous extract improves the antioxidant status in alloxan-induced diabetic rat tissues

This study investigates the effect of oral administration of an aqueous Enicostemma littorale whole plant extract on antioxidant defense in alloxan-induced diabetes in rats. A significant increase in blood glucose and increased concentration of thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) in liver, kidney and pancreas were observed in alloxan diabetic rats. Decreased concentration of reduced glutathione (GSH) and decreased activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were also observed in these tissues of diabetic rats. Oral administration of aqueous E. littorale whole plant extract (1 and 2 g/kg) to diabetic rats daily for 45 days significantly decreased blood glucose, TBARS, HP and increased GSH, SOD, catalase and GPx. E. littorale extract at the dose of 2 g/kg was more effective than 1 g/kg. Insulin (6 units/kg) administration to diabetic rats for 45 days brought back all the parameters to near normal status.     

Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine

Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague–Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.     

Fisetin,a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats

Oxidative stress is a biological entity quoted as accountable for several pathological conditions including diabetes mellitus. Chronic hyperglycemia in diabetes is associated with oxidative stress mediated tissue damage. The present study is aimed to explore the role of fisetin, in ameliorating hyperglycemia-mediated oxidative damage to liver in streptozotocin induced diabetic rats. In addition to the levels of blood glucose, plasma insulin, glycosylated hemoglobin, the extent of oxidative stress was assessed by hepatic lipid peroxides and hydroperoxides. The levels of reduced glutathione and the activities of enzymatic antioxidants were determined in the liver tissues. The activities of serum aminotransferases and alkaline phosphatase were assayed. A portion of liver was processed for histological and ultrastructural studies. Oral administration of fisetin (10 mg/kg b.w.) to diabetic rats decreased the levels of blood glucose and glycosylated hemoglobin and increased the plasma insulin level. A reduction in lipid peroxides and hydroperoxides were observed. The diminished activities of antioxidant enzymes and reduced glutathione in diabetic rats were improved upon fisetin administration. Thus, the results of the present study indicate that fisetin treatment protects the hepatocytes by improving the antioxidant competence in hepatic tissues of diabetic rats which is further evidenced from histological and ultra structural observations.     

Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA damage in Wistar rats

We have investigated the protective effect of quercetin (QN) against nicotine-induced prooxidant and antioxidant imbalance in circulation, lung, liver and kidney of experimental rats. The protective effect of QN was compared with N-acetylcysteine (NAC), a well-known antioxidant. Male albino rats of Wistar stain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and QN was given simultaneously by intragastric intubations for 22 weeks. The body weight gain of rats during experimental period was significantly decreased in nicotine treated group, whereas QN co-treated rats significantly increased in their body weight. The levels of lipid peroxidative indices viz., thiobarbituric acid reactive substances and hydroperoxides, and nitric oxide in circulation, lung, liver and kidney of nicotine-treated rats were increased significantly when compared to normal, which were brought down to near normal in QN co-treated group. Endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione were found to be significantly decreased in circulation, lung, liver and kidney of nicotine-treated group, which were significantly increased in QN-administered groups. The extent of DNA damage (evaluated by comet assay) was significantly increased in circulatory blood of nicotine-treated rats, which was effectively brought down by QN treatment. The protective effect of QN against nicotine toxicity was comparable to that of NAC. Our data suggest that QN exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the DNA in experimental animals.     

紫檀芪延缓糖尿病肾病发展的作用及机制

目的研究紫檀芪对链脲佐菌素(STZ)诱导的糖尿病肾病(DN)进展的延缓作用及可能机制。方法将C57BL/6J小鼠(n=50)随机分为对照组、模型组、低剂量药物组(20 mg·kg^-1)、中剂量药物组(40 mg·kg^-1)和高剂量药物组(80 mg·kg^-1),每组10只。对照组和模型组灌胃5 g·L^-1羧甲基纤维素钠,高、中、低剂量药物组小鼠灌胃相应剂量的紫檀芪12周。测定24 h蛋白尿,检测血液中血糖、血肌酐和血尿素氮水平,检测肾脏组织中炎症因子白介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的表达,HE染色和PAS染色检测肾脏组织的病理改变情况,Western blot法测定肾脏组织中沉默信息调节因子1(SIRT1)蛋白的表达。结果紫檀芪可延缓STZ诱导的1型DN的进展,降低血肌酐和血尿素氮的水平。紫檀芪对血糖及24 h尿蛋白无影响。紫檀芪可降低肾脏组织中炎症因子IL-6和MCP-1的表达。HE染色和PAS染色发现,紫檀芪能降低糖尿病小鼠肾小球体积和基底膜厚度,还能增加糖尿病小鼠肾脏组织中SIRT1蛋白的表达。结论紫檀芪可延缓1型DN的发展,其机制与其调节SIRT1的表达有关。