Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism

Thymoquinone (TQ) is the major active component of the volatile oil of Nigella sativa seeds. The effects of TQ on carbon tetrachloride (CCl4)-induced hepatotoxicity was investigated in male Swiss albino mice. Carbon tetrachloride (20 microliters/Kg, i.p.) injected into mice, induced damage to liver cells and was followed by the increase in serum alanine aminotransferase (ALT) activity after 24 h. Oral administration of TQ in a single dose (100 mg/Kg) resulted in significant (p < 0.001) protection against the hepatotoxic effects of CCl4. TQ was tested as a substrate for mice hepatic DT-diaphorase in the presence of NADH. TQ appears to undergo reduction to dihydrothymoquinone (DHTQ). Reduction rates as a function of protein (liver homogenate) and substrate (TQ) concentrations are reported. An apparent K(m) of 0.1 mM and an apparent Vmax of 74 mumol/min/g liver were measured. TQ and DHTQ inhibited the in vitro non-enzymatic lipid peroxidation in liver homogenate (induced by Fe(3+)-ascorbate) in a dose dependent manner. In this in vitro model DHTQ was more potent in comparison with TQ and butylated hydroxytoluene (BHT). The IC50 for DHTQ, TQ and BHT were found to be 0.34, 0.87 and 0.58 microM respectively. The data suggest that the in vivo protective action of TQ against CCl4-induced hepatotoxicity may be mediated through the combined antioxidant properties of TQ and its metabolite DHTQ.     

Effects of dietary vitamin E and selenium on antioxidative defense mechanisms in the liver of rats treated with high doses of glucocorticoid

The aim of this work was to determine the effects of dietary intake vitamin E and selenium (Se) on lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and on the antioxidative defense mechanisms in the liver of rats treated with high doses of prednisolone. Two hundred fifty adult male Wistar rats were randomly divided into five groups. The rats were fed a normal diet, but groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se, respectively, for 30 d. For 3 d subsequently, the control group (group 1) was treated with a placebo, and the remaining four groups were injected intramuscularly with 100 mg/kg body weight (BW) prednisolone. After the last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) enzymes and the levels of glutathione (GSH) and TBARS in their livers were measured. GSH-Px, SOD, and CAT enzyme activities and GSH levels in prednisolone-treatment group (group 2) began to decrease gradually at 4 h, falling respectively to 38%, 55%, and 40% of the control levels by 24 h, and recovering to the control levels at 48 h. In contrast, prednisolone administration caused an increase in the hepatic TBARS, reaching up to four times the levels of the control at 24 h. However, supplementation with vitamin E and Se had a preventive effect on the elevation of the hepatic TBARS and improved the diminished activities of the antioxidative enzymes and the levels of GSH. Therefore, the present study demonstrates the effectiveness of vitamin E and Se in reducing hepatic damage in glucocorticoid-treated rats and suggests that reductions in increased TBARS as a result of prednisolone may be an important factor in the action of vitamin E and Se.     

Do Zinc and Selenium Prevent the Antioxidant, Hepatic and Renal System Impairment Caused by Aspirin in Rats?

Aspirin is widely used as an antiinflammatory drug especially in children with rheumatic fever arthritis. The diminishing effects of aspirin on antioxidant enzymes and hepato-renal systems at high doses are well-known. It is now evident that the damage at antioxidant system worsens the clinical picture of the disease and prolongs the treatment time. Thus, we investigated the effect of antioxidant enzyme cofactors-zinc and selenium-supplementation on superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels (erythrocyte and liver) and hepato-renal toxicity during aspirin treatment at therapeutic doses. The rats were divided into five groups. The first and second groups were given aspirin 75 mg/kg/day and aspirin plus selenium (Selenium 200, selenium 200 mg tablet as selenium yeast, GNC) and zinc (Zinc 100, zinc 100 mg tablet as zinc gluconate, GNC), respectively, the third and fourth take 50 mg/kg/day aspirin and aspirin plus selenium and zinc twice a day, respectively. The fifth group was control. The rats were treated with aspirin for 5 weeks as in the treatment of rheumatic fever arthritis in children. Erythrocyte SOD and MDA levels were preserved with supplementation, whereas there was no change for GSH-Px levels. Liver SOD, GSH-Px, and MDA levels were not changed. In zinc- and selenium-supplemented groups, the levels of serum alanine aminotransferase, uric acid, and direct bilirubin levels were found statistically decreased compared with nonsupplemented groups. There was no significant histopathologic change in specimens of hepatic and renal tissues. Trace element supplementation may prevent free radical damage and shorten treatment time in children using long-term aspirin treatment.     

The effects of some antioxidant vitamin- and trace element-supplemented diets on activities of SOD, CAT, GSH-Px and LPO levels in chicken tissues

The effect of diets containing antioxidant vitamins and trace elements on chicken tissue activities of SOD, CAT, GSH-Px and of LPO levels was investigated. Chickens, 45 weeks of age were divided into six groups: control group, Cu group (13.2 mg Cu kg(-1) diet); Se group (0.07 mg Se kg(-l) diet); vitamin E group (70 mg DL-alpha-tocopherol acetate kg(-1) diet) and a constant level vitamin C, 200 mg kg(-1) diet); vitamin A group (240 mg retinol acetate kg(-1) diet) and vitamin C group (500 mg ascorbic acid kg(-1) diet). Significant variation of these antioxidant enzyme activities and LPO levels according to gender was demonstrated statistically. In the Cu group, CuZnSOD activity in the liver, erythrocyte, kidney and heart significantly increased by 75, 40, 12, 12% respectively (P<0.05). MnSOD activity in the heart, liver, kidney and brain of the vitamin C and in the heart of Cu group were found to be increased by approximately 15%, while in liver tissue of the Cu group it was reduced by 19% (P<0.05). GSH-Px activities in the Se, vitamin E and C groups were significantly increased, conversely LPO levels decreased (P<0.001). CAT activities in the liver and heart of the vitamin C group were significantly decreased (by 32%), but in kidney tissue only that of the Cu group was increased from 30.2 +/- 4.767 to 144.49 +/- 6.93 U mg(-1) P<0.001. The resistance to stress of the vitamin E and C groups, which had significantly increased activities of antioxidant enzymes and decreased lipid peroxide levels, were determined in 60% moisture medium at 45 degrees C.     

Comparison of melatonin, vitamin E and L-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide

This study was designed to evaluate and compare the effect of melatonin, vitamin E and L-carnitine on brain and liver oxidative stress and liver damage. Oxidative stress and hepatic failure were produced by a single dose of thioacetamide (TAA) (150 mg kg(-1)) in Wistar rats. A dose of either melatonin (3 mg kg(-1)) vitamin E (20 mg kg(-1) ) or L-carnitine (100 mg kg(-1)) was used. Blood samples were taken from the neck vasculature in order to determine ammonium, blood urea nitrogen (BUN) and liver enzymes. Lipid peroxidation products, glutathione (GSH) content and antioxidative enzymes were determined in cerebral and hepatic homogenates. The results showed a decrease in BUN and in the antioxidant enzymes activities and GSH in the brain and liver. Likewise, TAA induced significant enhancement of lipid peroxidation products levels in both liver and brain, as well as in ammonia values. Melatonin, vitamin E and L-carnitine, although melatonin more significantly, decreased the intensity of the changes produced by the administration of TAA alone. Furthermore melatonin combined with TAA, decreased the ammonia levels and increased the BUN values compared with TAA animals. Also it was more effective than vitamin E or L-carnitine in these actions. These data show the protective effect of these agents, especially melatonin, against oxidative stress and hepatic damage present in fulminant hepatic failure.     

Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome

In this study, we investigated the effects of erythropoietin (Epo), and pentoxifylline (Ptx) on the oxidant and antioxidant systems in the experimental short bowel syndrome. Spraque-Dawley rats were divided into four groups and all animals underwent 75% small bowel resection. Group E was treated with 500 IU kg(- 1) Epo subcutaneously (s.c.), group P with 50 mg kg(- 1) day(- 1) s.c. Ptx and group E+P with 500 IU kg(- 1) s.c. Epo plus 50 mg kg(- 1) day(- 1) s.c. Ptx for a period of 28 days. In group C, which is the control group, no drug treatment was given. At the end of 28 days the experimented rats were killed and ileum samples excised for biochemical and histopathological testing. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined in ileum homogenates. When compared to group C, the MDA and GSH-Px levels were significantly decreased (p < 0.05), but SOD activity was not changed (p > 0.05) in groups P and E+P, whereas both MDA and SOD and also GSH-Px activities were not changed significantly in group E (p > 0.05). The average villous length, crypt depth, muscular thickness and mucosal length were measured in all groups. The average crypt depth and mucosal length were statistically higher in the group P than group C (p < 0.001, p < 0.01, respectively). In addition, the crypt depth was statistically higher in both E and E+P groups as compared to group C (p < 0.001, p < 0.01, respectively). Therefore, our study indicates that Ptx may be more effective than Epo in reducing lipid peroxidation. Moreover, we considered that Ptx may give this protective effect by inhibiting the free oxygen radicals to a greater extent than developing the antioxidant capacity.     

17β-Estradiol and Vitamin E Modulates Oxidative Stress-Induced Kidney Toxicity in Diabetic Ovariectomized Rat

The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40?μg?kg(-1)/day) and alpha-tocopherol (100?μg?kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4?weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.     

Effects of extract of Ginkgo biloba leaves and its constituents on carcinogen-metabolizing enzyme activities and glutathione levels in mouse liver

The effects of a standardized extract of Ginkgo biloba L. leaves (EGb) and its terpene constituents, bilobalide and ginkgolides, on the activities of detoxification enzymes, i.e., glutathione S-transferases (GSTs) and DT-diaphorase, and glutathione contents, were investigated in the mouse liver. Oral treatment with EGb (100-1,000 mg/kg) and bilobalide (10-30 mg/kg) once a day for 4 days caused a dose-dependent elevation in GST activity. Ginkgolide A (30 mg/kg, for 4 days) also significantly elevated GST activity, whereas ginkgolide B and ginkgolide C at the same dose had no effects. EGb significantly increased the protein level of GST pi, and bilobalide significantly increased those of GST alpha and GST mu Moreover, EGb-treatment and bilobalide-treatment caused significant elevations in DT-diaphorase activity and in hepatic glutathione contents.     

Dietary High Vanadium Causes Oxidative Damage-Induced Renal and Hepatic Toxicity in Broilers

The purpose of this study was to investigate the renal and hepatic oxidative damage and toxicity caused by dietary high vanadium in broilers. A total of 420 one-day-old avian broilers were divided into six groups and fed on a corn–soybean basal diet as control diet (vanadium 0.073 mg/kg), and five high vanadium diets (vanadium 5 mg/kg, high vanadium group I; 15 mg/kg, high vanadium group II; 30 mg/kg, high vanadium group III; 45 mg/kg, high vanadium group IV; and 60 mg/kg, high vanadium group V) throughout the experimental period of 42 days. The results showed that the renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxy radical, and malondialdehyde (MDA), glutathione, and vanadium contents were not significantly changed in high vanadium group I and II when compared with those of the control groups. However, the SOD and GSH-Px activities, ability to inhibit hydroxy radical, and GSH content were significantly decreased, and the MDA and vanadium contents were markedly increased in high vanadium groups III, IV, and V. At the same time, the lesions were also observed in the kidney and liver of high vanadium groups III, IV, and V. The renal tubular epithelial cells showed granular degeneration and vacuolar degeneration, and hepatocytes showed granular degeneration, vacuolar degeneration, and fatty degeneration. It was concluded that dietary vanadium in the range of 30–60 mg/kg could cause oxidative damage and vanadium accumulation, which induced renal and hepatic toxicity and lesions. The renal and hepatic function was finally impaired in boilers.     

Effect of oral vitamin E supplementation on oxidative stress in guinea-pigs with short-term hypothermia

Effects of oral vitamin E supplementation on blood malondialdehyde (MDA), glutathione (GSH) and vitamin E levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities in acute hypothermia of guinea-pigs were investigated. Thirty male guinea pigs, weighing 500-800 g were randomly divided into one of three experimental groups: A (control, without cooling), B (hypothermic) and C (hypothermic with vitamin E supplementation). The guinea-pigs of group C received daily oral supplementation of 460 mg kg(-1) bw vitamin E for 4 days before inducing hypothermia. Twenty-four hours after the last vitamin E supplementation, the guinea-pigs of the B and C groups were cooled by immersion into cold water (10-12 degrees C), and the control guinea-pigs were immersed into water of body temperature (37 degrees C) up to the neck for 5 min without using any anaesthetic or tranquilizer. Rectal body temperatures of groups were measured and blood samples for biochemical analysis were collected immediately after the cooling. The body temperature, GSH and vitamin E levels and GSH-Px enzyme activity of hypothermic guinea-pigs were lower (p < 0.05), but SOD enzyme activity was not different (p > 0.05) from those of control animals. Although, the body temperature of hypothermic with vitamin E supplementation group was lower (p < 0.05), all other parameters of this group were not different (p > 0.05) from the controls. It was concluded that oral supplementation of vitamin E can alleviate the lipid peroxidation-induced disturbances associated with hypothermia by increasing the serum vitamin E level to normal. However, more studies are needed to prove whether this vitamin can improve quality of life during the cold seasons.     

The protective mechanisms of defibrotide on liver ischaemia-reperfusion injury

During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia-reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45 min of portal occlusion. DEF 175 mg/kg(-1) was infused before ischaemia in 10 ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p < 0.01 and p < 0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p < 0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p < 0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels.     

Gluconeogenesis and ketogenesis in perfused liver of rats submitted to short-term insulin-induced hypoglycaemia

Gluconeogenesis and ketogenesis of in situ rat perfused liver submitted to short-term insulin-induced hypoglycaemia (IIH) were investigated. For this purpose, 24-h fasted rats that received intraperitoneal (ip) regular insulin (1.0 U kg(-1)) or saline were compared. The studies were performed 30 min after insulin (IIH group) or saline (COG group) injection. For gluconeogenesis studies, livers from the IIH and COG groups were perfused with increasing concentrations (from basal blood concentrations until saturating concentration) of glycerol, L-lactate (Lac) or pyruvate (Pyr). Livers of the IIH group showed maintained efficiency to produce glucose from glycerol and higher efficiency to produce glucose from Lac and Pyr. In agreement with these results the oral administration of glycerol (100 mg kg(-1)), Lac (100 mg kg(-1)), Pyr (100 mg kg(-1)) or glycerol (100 mg kg(-1)) + Lac (100 mg kg(-1)) + Pyr (100 mg kg(-1)) promoted glycaemia recovery. It can be inferred that the increased portal availability of Lac, Pyr and glycerol could help glycaemia recovery by a mechanism mediated, partly at least, by a maintained (glycerol) or increased (Lac and Pyr) hepatic efficiency to produce glucose. Moreover, in spite of the fact that insulin inhibits ketogenesis, the capacity of the liver to produce ketone bodies from octanoate during IIH was maintained.     

Detection of ischemia-reperfusion cardiac injury by cardiac muscle chemiluminescence

Various methods have been used in the past to assess the implication of oxygen free radicals (OFR) in ischemia-reperfusion-induced cardiac injury. Luminol-enhanced tert-butyl-initiated chemiluminescence in cardiac tissue reflects oxidative stress and is a very sensitive method. It was used to elucidate the role of OFR in cardiac injury due to ischemia and reperfusion. Studies were conducted on perfused isolated rabbit hearts in three groups (n = 8 in each): I, control; II, submitted to global ischemia for 30 min; III, submitted to ischemia for 30 min followed by reperfusion for 60 min. The heart tissue was then assayed for chemiluminescence (CL); content of malondialdehyde (MDA), an indicator of OFR-induced cardiac injury; and activity of tissue levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)].The control values for left and right ventricular CL and malondialdehyde were 81.1 ± 15.4 (S.E.) and 182.4 ± 50.3 (S.E.), mv-min-mg protein^–1; and 0.024 ± 0.006 (S.E.) and 0.324 ± 0.005 (S.E.) nmoles-mg protein^–1 respectively. Ischemia produced an increase in the cardiac CL (3.3 to 4.4 fold) and MDA content (2 to 2.6 fold). Reperfusion following ischemia also produced similar changes in CL and MDA content. The control values for activity of left ventricular SOD, catalase, and GSH-Px were 45.77 ± 1.73 (S.E.) U-mg protein^–1 5.35 ± 0.51 (S.E.) K-10^–3-sec^–1-mg protein^–1, and 77.50 ± 7.70 (S.E.) nmoles NADPH-min^–1-mg protein^–1 respectively. Activities of SOD and catalase decreased during ischemia but were similar to control values in ischemic-reperfused hearts. The GSH-Px activity of left ventricle was unaffected by ischemia, and ischemia-reperfusion. GSH-Px activity of the right ventricle increased with ischemia, and ischemic-reperfusion.These results indicate that cardiac tissue chemiluminescence would be a useful and sensitive tool for the detection of oxygen free radical-induced cardiac injury.     

The effect of melatonin against oxidative damage during total-body irradiation in rats

Melatonin has been reported to participate in the regulation of a number of important physiological and pathological processes. Melatonin, which is a powerful endogenous antioxidant, may play a role in the prevention of oxidative damage. The aim of this study was to investigate the effect of pretreatment with melatonin (5 mg kg(-1) and 10 mg kg(-1)) on gamma-radiation-induced oxidative damage in plasma and erythrocytes after total-body irradiation with a single dose of 5 Gy. Total-body irradiation resulted in a significant increase in plasma and erythrocyte MDA levels. Melatonin alone increased the levels of SOD and GSH-Px. Erythrocyte and plasma MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg kg(-1)) were significantly lower than those in rats that were not pretreated. There was no significant difference between the effects of 5 and 10 mg kg(-1) on plasma MDA activities and CAT activities. However, erythrocyte MDA levels showed a dose-dependent decrease, while GSH-Px activities increased with dose. Our study suggests that melatonin administered prior to irradiation may protect against the damage produced by radiation by the up-regulation of antioxidant enzymes and by scavenging free radicals generated by ionizing radiation.     

Effects of photodynamic treatment on biological antioxidant systems in rats

Effects of photodynamic treatments on inherent antioxidant metabolites and cellular defence enzymes have been investigated in rats. Wistar rats were grouped into untreated controls, light controls, hematoporphyrin derivative (Hpd) (treated with 5 and 10 mg Hpd/kg body weight and kept in dark) and sets treated with both Hpd and red light (dose 172 and 344 j/m2 ). After 2, 24, 48 and 72 hr of Hpd injection the rats sacrificed, livers quickly excised to analyze Hpd uptake, activities of enzymes like catalase, GSH-Px and antioxidants like GSH, vitamin A, vitamin E and vitamin C. The results showed that the loss of Hpd from liver as a function of post- injection time was non- linear. An increased generation of lipid radicals was observed in the groups treated with 5 mg Hpd and higher dose of light and in groups treated with 10 mg Hpd at both the doses of light. Combination of light and Hpd reduced hepatic GSH content with a concomitant reduction in GSH-Px. At higher doses of Hpd and light, there was a significant reduction in hepatic vitamin A levels. Combination of Hpd and light in all doses reduced vitamin E content in liver. The decreased biological antioxidant contents and GSH-Px may be attributed to their utilization for the scavenging of free radicals generated by Hpd and light in tissues. However, no change in catalase activity and vitamin C content in liver was noted in experimental rats. The results suggest that exposure to higher doses of Hpd with light alters oxidant stress system and TBARS content in rat.     

阿里红黄酮对衰老模型小鼠的抗衰老作用

目的：研究阿里红黄酮对衰老模型小鼠的抗衰老作用。方法：将小鼠随机分为6组（n=12）：正常对照组,衰老模型组,阳性对照组,低、中、高剂量阿里红黄酮组。除正常对照组外,其余各组均采用D-半乳糖颈背部皮下注射建立亚急性衰老小鼠模型,用不同剂量的阿里红黄酮（100、200和400 mg/（kg·d））灌服小鼠6周后,计算衰老模型小鼠脑指数及脾脏指数、胸腺指数,测定其脑组织丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GSH-Px）活性、肝组织过氧化氢酶（CAT）及超氧化物歧化酶（SOD）活性。结果：阿里红黄酮3个剂量组可不同程度的升高衰老模型小鼠的脑指数、脾脏指数、胸腺指数、脑组织中的GSH-Px活性及肝组织中的CAT、SOD活性,降低其脑组织中的MDA含量。结论：阿里红黄酮可能通过提高机体的抗氧化能力而达到抗衰老作用。     

Reduction of Brain Antioxidant Defense Upon Treatment with Butylated Hydroxyanisole (BHA) and Sudan III in Syrian Golden Hamster

Treatment with the antioxidant butylated hydroxyanisole (BHA) or the azo dye Sudan III during two weeks led to changes in the brain enzymatic antioxidant defense of Syrian golden hamsters. BHA was able to induce liver superoxide dismutase (SOD) 2-fold but had no effect on the brain SOD activity, whereas SOD activity was reduced to 50% in brain and remained unchanged in liver with Sudan III. These two substances are known inducers of DT-diaphorase and in fact this enzymatic activity was induced 4- and 6-fold in liver with BHA and Sudan III, respectively. However, BHA promoted a significant 40% reduction, whereas no change was observed with Sudan III in brain DT-diaphorase activity. Glutathione(GSH)-related enzymatic activities were also assayed in brain and liver. No induction was observed with BHA or Sudan III for any of the activities tested in hamster brain: GSH S-transferase (GST), GSH peroxidase (GSH-Px) and glutathione disulfide (GSSG) reductase (GR). Only 1.3- and 1. 4-fold increases of GST and GR activities were observed in liver and no change in any of these enzymatic activities in brain with BHA; a partial limitation of permeability to BHA of the blood-brain barrier may explain this results. Furthermore, Sudan III promoted reductions in all these GSH-related enzymatic activities in brain and liver. The possible explanations for these results are discussed.Deceased 4th November 1998     

达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2及葡萄糖转运蛋白4基因表达的影响*

目的:探讨达格列净对2型糖尿病大鼠肾脏葡萄糖转运蛋白2(GLUT2)和葡萄糖转运蛋白4(GLUT4)基因表达的影响。方法:使用高脂饲料和一次性注射40 mg/kg链脲佐菌素(STZ)建立2型糖尿病大鼠模型,造模大鼠以空腹血糖(FBG)含量≥16.7 mmol/L时视为造模成功。造模成功后随机分为模型组(B组,生理盐水)、达格列净低剂量组(C组,0.75 mg/kg)、达格列净中剂量组(D组,1.5 mg/kg)、达格列净高剂量组(E组,3.0 mg/kg),每组6只;另选取6只健康的SD大鼠作为正常对照组(A组,生理盐水)。各组均为灌胃给药,每天1次,连续7周。灌胃给药7周后测定大鼠的体重以及血清FBG、糖化血红蛋白(HbA1c)、血尿素氮(BUN)、血肌酐(Scr)的变化;采用酶联免疫吸附测定血清及肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px);采用HE观察肾脏病理学变化;采用Western blot检测肾脏组织中GLUT2、GLUT4蛋白表达;RT-qPCR检测肾脏组织中GLUT2、GLUT4 mRNA相对表达量。结果: 与A组比较,各组大鼠的体重及SOD、GSH-PX水平明显降低(P＜ 0.05),FBG、HbA1c、BUN、Scr、MDA水平明显升高(P＜0.05),肾脏病理损伤严重,肾组织GLUT2、GLUT4 mRNA相对表达量和蛋白表达均明显降低(P均＜0.05)。与B组比较,C组、D组和E组大鼠的体重、SOD、GSH-PX水平和肾组织GLUT2、GLUT4 mRNA相对表达量明显升高(P＜0.05),FBG、HbA1c、BUN、Scr、MDA水平明显降低(P＜ 0.05);D组和E组肾脏病理损伤明显减轻,肾组织GLUT2、GLUT4蛋白表达均明显升高(P均＜0.05)。结论:达格列净可缓解2型糖尿病模型大鼠的病情,并上调肾脏GLUT2及GLUT4基因的表达。     

Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study

We investigated the antihypertensive and antioxidant potential of vanillic acid (VA) in N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) - treated adult male albino Wistar rats. Treatment of rats with L-NAME (40 mg/kg Bw for 30 days) caused a sustained increase in systolic- (SBP) and diastolic blood pressure (DBP) and significantly decreased the concentration of nitrite/nitrate (NO(x)) in plasma as compared with that in the control. Rats treated with VA restored SBP and DBP to normal level and preserve the plasma NO metabolites concentration. Moreover, VA reduced lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) and significantly restored enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase), non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma. To assess the toxicity if any of VA treatment, hepatic and renal function markers were measured. Our results showed that the effect at a dose of 50 mg/kg Bw of VA was more pronounced than that of the other two doses, 25 and 100 mg/kg Bw. These results were supported by histopathology studies. We conclude that VA possesses an antihypertensive and antioxidant activity in L-NAME-induced hypertensive rats.     

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.