THE VARIATION OF ANTIOXIDANT DEFENSE SYSTEM OF Streptomyces sp. M4018 WITH RESPECT TO CARBON SOURCES

The effect of glycerol, glucose, and starch as carbon sources on the antioxidant defense system such as superoxide dismutase (SOD) and catalase (CAT) activities, pyruvate levels, and membrane lipid peroxidation (LPO) levels of Streptomyces sp. M4018, after isolation from the rhizosphere samples of Colutea arborescens and identification as a strain of S. hiroshimensis based on phenotypic and genotypic characteristics, were investigated. As an antioxidant defense enzyme, SOD activities increased up to 20 g/L of glycerol and 15 g/L of starch, while they showed negative correlation with glucose concentration. CAT activity variations of glycerol- and glucose-supplemented mediums showed significant positive correlations with the trend of SOD activities. However, CAT activity, in contrast to SOD, in Streptomyces sp. M4018 tended to decrease as the starch concentration increased. The production of pyruvate increased with respect to glycerol and starch up to 15 g/L, while it was positively correlated with glucose concentration. The highest pyruvate production was seen at 20 g/L glucose. Membrane LPO levels were negatively correlated with the activities of SOD and CAT enzymes, and the minimum LPO level was determined at 5 g/L of glucose, where SOD and CAT activities reached their maximum levels. Nevertheless, the higher SOD and CAT activities in a wider range of incubation period compared to the beginning by resulting in insignificant increases in membrane LPO levels showed the unusual antioxidant response capacities of the in Streptomyces sp. M4018 against the potentially deleterious effects of reactive oxygen species (ROS) for glycerol, glucose, and starch as carbon sources.     

Melatonin reduces oxidative stress induced by ochratoxin A in rat liver and kidney

Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by ochratoxin A (OTA) administration in rats was investigated. Four groups of 15 rats each were used: controls, MEL-treated rats (5 mg/kg body mass), OTA-treated rats (250 μg/kg) and MEL+OTA-treated rats. After 4 weeks of treatment, the levels of malondialdehyde (MDA), a lipid peroxidation product (LPO) were measured in serum and homogenates of liver and kidney. Also, the levels of glutathione (GSH), and activities of glutathione reductase (GR), glutathione peroxidase (GSPx), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in liver and kidney were determined. In OTA-treated rats, the levels of LPO in serum and in both liver and kidney were significantly increased compared to levels in controls. Concomitantly, the levels of GSH and enzyme activities of SOD, CAT, GSPx and GR in both liver and kidney were significantly decreased in comparison with controls. In rats received MEL+OTA, the changes in the levels of LPO in serum and in liver and kidney were not statistically significant compared to controls. Concomitantly, the levels of GSPx, GR and GST activities in both liver and kidney tissues were significantly increased in comparison with controls. Similar increases in GSPx, GR and GST activities were also observed in MEL-treated rats when compared with controls. In conclusion, the oxidative stress may be a major mechanism for the toxicity of OTA. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and stimulation of GST activities. Thus, clinical application of melatonin as therapy should be considered in cases of ochratoxicosis.     

The variation of antioxidant defense system of Streptomyces sp. M4018 with respect to carbon sources

The effect of glycerol, glucose, and starch as carbon sources on the antioxidant defense system such as superoxide dismutase (SOD) and catalase (CAT) activities, pyruvate levels, and membrane lipid peroxidation (LPO) levels of Streptomyces sp. M4018, after isolation from the rhizosphere samples of Colutea arborescens and identification as a strain of S. hiroshimensis based on phenotypic and genotypic characteristics, were investigated. As an antioxidant defense enzyme, SOD activities increased up to 20 g/L of glycerol and 15 g/L of starch, while they showed negative correlation with glucose concentration. CAT activity variations of glycerol- and glucose-supplemented mediums showed significant positive correlations with the trend of SOD activities. However, CAT activity, in contrast to SOD, in Streptomyces sp. M4018 tended to decrease as the starch concentration increased. The production of pyruvate increased with respect to glycerol and starch up to 15 g/L, while it was positively correlated with glucose concentration. The highest pyruvate production was seen at 20 g/L glucose. Membrane LPO levels were negatively correlated with the activities of SOD and CAT enzymes, and the minimum LPO level was determined at 5 g/L of glucose, where SOD and CAT activities reached their maximum levels. Nevertheless, the higher SOD and CAT activities in a wider range of incubation period compared to the beginning by resulting in insignificant increases in membrane LPO levels showed the unusual antioxidant response capacities of the in Streptomyces sp. M4018 against the potentially deleterious effects of reactive oxygen species (ROS) for glycerol, glucose, and starch as carbon sources.     

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.     

Investigation of in vitro and in vivo antioxidant potential of secoisolariciresinol diglucoside

The present study was designed to evaluate the in vitro and in vivo ameliorative antioxidant potential of secoisolariciresinol diglucoside (SDG). In vitro antioxidant activity of synthetic SDG was carried out using DPPH, reducing power potency, and DNA protection assays. Wistar albino rats weighing 180–220 g were used for in vivo studies and liver damage was induced in the experimental animals by a single intraperitoneal (I.P.) injection of CCl₄ (2 g/kg b.w.). Intoxicated animals were treated orally with synthetic SDG at (12.5 and 25 mg/kg b.w.) and Silymarin (25 mg/kg) for 14 consecutive days. The levels of catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), and lipid peroxidase (LPO) were measured in liver and kidney homogenates. The synthetic SDG exerts high in vitro antioxidant potency as it could scavenge DPPH at a IC₅₀ value of 78.9 μg/ml and has dose-dependent reducing power potency and protected DNA at 0.5 mg/ml concentration. Oral administration of synthetic SDG at 12.5 and 25 mg/kg b.w. showed significant protection compared to Silymarin (25 mg/kg) and the activities of CAT, SOD, and POX were markedly increased (P < 0.05), whereas LPO significantly decreased (P < 0.001) in a dose-dependent manner in liver and kidney in both pre- and post-treatment groups when compared to toxin-treated group. The results of in vitro and in vivo investigations revealed that synthetic SDG at 25 mg/kg b.w. is associated with beneficial changes in hepatic enzyme activities and thereby plays a key role in the prevention of oxidative damage in immunologic system.     

Seasonal changes in antioxidant defence system of liver and gills of Salmo trutta caspius, Salmo trutta labrax and Salmo trutta macrostigma

Seasonal changes in antioxidant enzyme activities (superoxide dismutase, SOD, EC 1.15.1.1; catalase, CAT, EC 1.11.1.16; glutathione peroxidase, GPx, EC 1.11.1.9; glutathione reductase, GR, EC 1.6.4.2; glucose-6-phosphate dehydrogenase, G6PD, EC 1.1.1.49 and glutathione S -transferase, GST, EC 1.5.1.18) and lipid peroxidation (LPO) levels of livers and gills of female Caspian trout Salmo trutta caspius , Black Sea trout Salmo trutta labrax and mountain trout Salmo trutta macrostigma were investigated. SOD, CAT, GPx, G6PD and GST activities were higher in liver compared to gills of all sub-species; concomitantly, the GR activity was also higher in the livers of S. t. caspius and S. t. labrax , but the reverse was seen in S. t. macrostigma . LPO levels were higher in the gills compared to the liver of all sub-species. There was no general trend in the seasonal changes in the gill antioxidant enzyme (AE) activities or LPO levels. Higher AE activities, however, were found in the liver of each sub-species during autumn, and this coincided with an increase in the gonado-somatic index.     

Effect of ruthenium complexes on the activities of succinate dehydrogenase and cytochrome oxidase

In this article, we report the effects of acute administration of ruthenium complexes, trans-[RuCl(2)(nic)(4)] (nic=3-pyridinecarboxylic acid) 180.7 micromol/kg (complex I), trans-[RuCl(2)(i-nic)(4)] (i-nic=4-pyridinecarboxylic acid) 13.6 micromol/kg (complex II), trans-[RuCl(2)(dinic)(4)] (dinic=3,5-pyridinedicarboxylic acid) 180.7 micromol/kg (complex III) and trans-[RuCl(2)(i-dinic)(4)]Cl (i-dinic=3,4-pyridinedicarboxylic acid) 180.7 micromol/kg (complex IV) on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) activities in brain (hippocampus, striatum and cerebral cortex), heart, skeletal muscle, liver and kidney of rats. Our results showed that complex I inhibited SDH activity in hippocampus, cerebral cortex, heart and liver; and inhibited COX in heart and kidney. Complex II inhibited SDH in heart and hippocampus; COX was inhibited in hippocampus, heart, liver and kidney. SDH activity was inhibited by complex III in heart, muscle, liver and kidney. However, COX activity was increased in hippocampus, striatum, cerebral cortex and kidney. Complex IV inhibited SDH activity in muscle and liver; COX activity was inhibited in kidney and increased in hippocampus, striatum and cerebral cortex. In a general manner, the complexes tested in this work decrease the activities of SDH and COX in heart, skeletal muscle, liver and kidney. In brain, complexes I and II were shown to be inhibitors and complexes III and IV activators of these enzymes. In vitro studies showed that the ruthenium complexes III and IV did not alter COX activity in kidney, but activated the enzyme in hippocampus, striatum and cerebral cortex, suggesting that these complexes present a direct action on COX in brain.     

Reactive oxygen species generation is modulated by mitochondrial kinases: correlation with mitochondrial antioxidant peroxidases in rat tissues

Mitochondrial hexokinase (mt-HK) and creatine kinase (mt-CK) activities have been recently proposed to reduce the rate of mitochondrial ROS generation through an ADP re-cycling mechanism. Here, we determined the role of mt-HK and mt-CK activities in regulate mitochondrial ROS generation in rat brain, kidney, heart and liver, relating them to the levels of classical antioxidant enzymes. The activities of both kinases were significantly higher in the brain than in other tissues, whereas the activities of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were higher in both liver and kidney mitochondria. In contrast, manganese superoxide dismutase (Mn-SOD) activity was not significantly different among these tissues. Activation of mitochondrial kinases by addition of their substrates increased the ADP re-cycling and thus the respiration by enhancing the oxidative phosphorylation. Succinate induced hydrogen peroxide (H(2)O(2)) generation was higher in brain than in kidney and heart mitochondria, and the lowest in liver mitochondria. Mitochondrial membrane potential (DeltaPsi(m)) and H(2)O(2) production, decreased with additions of 2-DOG or Cr to respiring brain and kidney mitochondria but not to liver. The inhibition of H(2)O(2) production by 2-DOG and Cr correspond to almost 100% in rat brain and about 70% in kidney mitochondria. Together our data suggest that mitochondrial kinases activities are potent preventive antioxidant mechanism in mitochondria with low peroxidase activities, complementing the classical antioxidant enzymes against oxidative stress.     

The relationship between total sialic acid levels and antioxidant status in the tadpoles of Bufo viridis and Rana ridibunda ridibunda

Total sialic acid levels (TSA), antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) levels were investigated during the developmental period in tadpoles of the predominantly terrestrial amphibian B. viridis and the predominantly aquatic amphibian R. r. ridibunda. Maximum TSA levels were observed in B. viridis and R. r. ridibunda at the fifth and third week of their development, respectively. SOD and CAT activity variations during development in B. viridis were higher than in R. r. ridibunda. Although SOD activity in B. viridis was higher than R. r. ridibunda at the eighth week, SOD activity increased 19.2-fold in R. r. ridibunda and 10.4-fold in B. viridis between the first and eighth week. CAT activity in R. r. ridibunda did not significantly change (p>0.001) until the fifth week then increased, whereas in B. viridis CAT increased after the third week. In contrast to the rise in the antioxidant enzyme activities, LPO levels tended to decrease during the developmental period. Levels of LPO showed a similar trend until the third week for both species. The minimum LPO levels in B. viridis and R. r. ridibunda were 23+/-1.2 and 146+/-7.3 nmol MDA g(-1) tissue, at the eighth week, respectively. While decreasing LPO levels correlated with increasing antioxidant enzyme activities, TSA tended to decrease after reaching a maximum point.     

Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton’s lymphoma-bearing mice

Cisplatin treatment of tumor-bearing mice and analysis of ultrastructural features of mitochondria in the kidney and Dalton’s lymphoma cells showed the appearance of more roundish mitochondria with thickened membranes. It also caused the reduction in the number and irregularity in the shape of cristae and formation of vacuoles in the mitochondria. After cisplatin treatment, decreased level of protein, succinate dehydrogenase activity, and increased level of lipid peroxidation were noted in Dalton’s lymphoma tumor cells and kidney. Cisplatin-mediated decrease in SDH activity, GSH level and an increase in LPO in the mitochondria of kidney could play an important role to produce nephrotoxicity. However, in DL cells, decrease in cellular GSH could be noteworthy than mt-GSH, along with decrease in SDH activity and increase in LPO in the cisplatin-mediated anticancer activity. These changes could play an important role to produce both the cisplatin-mediated effects i.e. anticancer activity and nephrotoxicity. Cisplatin-induced biochemical and ultrastructural changes in mitochondria after cisplatin treatment should be an important factor in the development of biochemical injury in mitochondria and affecting the overall metabolism in the cells. The findings from the present studies indicate multilevel effect of cisplatin in the cells and do support the earlier view that mitochondria could be a critical target in cisplatin-mediated anticancer activity and toxicity in the hosts.     

Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities.     

Myocardial antioxidant status and oxidative stress after combined action of exercise training and ethanol in two different age groups of male albino rats

The interaction of exercise training and ethanol on the myocardial antioxidant enzymes and the oxidative stress markers was investigated in the Wistar strain male albino rats. We also tested the interactive effects of exercise training and ethanol on the age-associated free radical production and antioxidant defense system. We found a significant decrease (p<0.05) in the activity levels of superoxide dismutase (SOD) and catalase (CAT) in the myocardium of old rats when compared to young rats by 26% and 58%, respectively, suggesting the onset of age-dependent decrease in the myocardial antioxidant enzyme system. In contrast to the decreased antioxidant enzyme activity, xanthine oxidase (XOD) and lipid peroxidation (LPO) levels were elevated, suggesting the age-induced oxidative stress. Exercise training significantly (p < 0.05) elevated the activities of SOD, CAT, XOD and LPO levels in both the age groups of animals. Ethanol consumption significantly lowered the SOD and CAT activities in both the age groups, whereas a significant increase was observed in the XOD and LPO levels. In contrast, the combination of exercise training plus ethanol lowered XOD and LPO levels in both the age groups of rats compared to ethanol treated rats. A significant (p < 0.05) increase in the activities of SOD and CAT was reported in the rats treated with the combination of exercise training plus ethanol. This increase was more pronounced in the younger rats than the older rats. The findings of the present investigation on the potential role of antioxidant enzymes to counter the ethanol-induced pro-oxidants showed an increase with the interaction of exercise training. With age, a decrease in the antioxidant enzyme capacity was observed. This reveals that the old age rats were more affected to the pro-oxidants when compared to the young age rats. In conclusion it is demonstrated that two months treadmill endurance exercise training is beneficial to both young and old rats in improving antioxidant defense to challenge the oxidative stress in the myocardial tissue and thereby successfully countering the free radical production due to ethanol intoxication.     

Melatonin and schistosomal antigens ameliorate the anti-oxidative and biochemical response to Schistosoma mansoni infection in hamster

The present study was designed to investigate the potential protective effect of melatonin as an antioxidant separately or in combination with antigens (cercarial; CAP or soluble worm; SWAP) against Schistosoma mansoni infection in hamsters. Each hamster was sensitized with an initial immunization of 0.6 ml of the extracted antigen (30 μg protein/mL). After four days,a second injection of 0.4 mL was given (20 μg protein/mL). Then,each hamster was exposed to 260±20 S.mansoni cercariae followed with melatonin...     

Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats

Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.     

Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin

This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme activity in blood, liver, and kidney, as well as on lipid peroxidation and delta aminolevulinic dehydratase (δ-ALA-D) activity, and a histopathological analysis of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 6): control/saline (C); control/curcumin (CCur); diabetic/saline (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and diabetic/insulin/curcumin (DInsCur). After 30 days of treatment with curcumin and/or insulin, the animals were sacrificed and the liver, kidney, and serum were used for experimental determinations. Results of histopathological analysis showed that the treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. TBARS levels were significantly increased in serum, liver, and kidney in D group and the administration of curcumin and insulin prevented this increase in DIns and DCur groups. The activities of catalase (CAT), superoxide dismutase, and δ-ALA-D presented a significant decrease in the liver and kidney D group when compared to C group (P < 0.05). The animals treated with curcumin and insulin presented an increase of CAT activity, revealing a positive interaction between both substances. The treatments with curcumin or insulin prevented oxidative stress in blood, through modulation of enzymatic antioxidant defenses. These findings contributed to the comprehension that antioxidants from medicinal plants could be used as adjuvant in the treatment of this endocrinopathy and not as single therapy.     

黄河上游环境污染对花背蟾蜍抗氧化酶活性及丙二醛含量的影响

选择黄河上游污染程度较严重的兰州地区和相对无污染的刘家峡地区作为研究样点,比较分析了两地花背蟾蜍（Bufo raddei）肝脏和肾脏中抗氧化酶SOD、CAT和GPx活性及丙二醛（MDA）含量。与刘家峡地区相比,兰州地区花背蟾蜍肝脏的SOD活性升高,CAT和GPx活性极显著降低,肾脏GPx活性显著增高,肝脏和肾脏MDA含量明显高于刘家峡。结果表明,黄河上游环境污染使得花背蟾蜍体内氧化胁迫加重,导致其组织脂质过氧化程度升高。     

Diurnal changes in succinate and D-3-hydroxybutyrate dehydrogenase activities of rat liver mitochondria after chronic alcohol consumption and withdrawal

1. The succinate dehydrogenase (SDH) and D-3-hydroxybutyrate dehydrogenase (HBDH) activities were measured over a 24-hr period in rat liver mitochondria after chronic alcohol ingestion and withdrawal. 2. The diurnal patterns of both the enzyme activities were shown to change after alcohol consumption, with 64-66% decrease in the daily mean levels. 3. The diurnal rhythms of the SDH and HBDH activities are partially restored 24-72 hr after alcohol withdrawal. 4. There was no correlation between changes in both the enzyme activities and the NAD+/NADH ratio of liver mitochondria from control, ethanol-fed and withdrawn rats over the day.     

The effects of oxidative stress in urinary tract infection during pregnancy

The purpose of this study was to determine the effect of urinary tract infection (UTI) on antioxidant systems and lipid peroxidation (LPO) levels during pregnancy. We also investigated if these antioxidant systems and LPO levels differed in each trimester. One hundred forty-three nonpregnant women, as a control group, and 77 pregnant women were included in the study. Urine cultures were performed according to standard techniques. Catalase (CAT), superoxide dismutase (SOD), and LPO levels were measured using a spectrophotometer. UTI was observed in 14 of 77 pregnant women and the isolated microorganisms were Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus. CAT, SOD, and LPO levels were increased in pregnant women compared with nonpregnant women (P<.01). CAT, SOD activities, and LPO levels were increased from the first trimester to the third trimester in pregnancy without UTI. However, CAT and SOD activities were decreased, LPO levels were increased from the first trimester to the third trimester in pregnancy with UTI (P<.01). Pregnancy causes oxidative stress and also UTI during pregnancy may aggravate oxidative stress.     

Mitochondrial Modulation by Epigallocatechin 3-Gallate Ameliorates Cisplatin Induced Renal Injury through Decreasing Oxidative/Nitrative Stress,Inflammation and NF-kB in Mice

Cancer chemotherapy drug cisplatin is known for its nephrotoxicity. The aim of this study is to investigate whether Epigallocatechin 3-Gallate (EGCG) can reduce cisplatin mediated side effect in kidney and to understand its mechanism of protection against tissue injury. We used a well-established 3-day cisplatin induced nephrotoxicity mice model where EGCG were administered. EGCG is a major active compound in Green Tea and have strong anti-oxidant and anti-inflammatory properties. EGCG protected against cisplatin induced renal dysfunction as measured by serum creatinine and blood urea nitrogen (BUN). EGCG improved cisplatin induced kidney structural damages such as tubular dilatation, cast formation, granulovaculoar degeneration and tubular cell necrosis as evident by PAS staining. Cisplatin induced kidney specific mitochondrial oxidative stress, impaired activities of mitochondrial electron transport chain enzyme complexes, impaired anti-oxidant defense enzyme activities such as glutathione peroxidase (GPX) and manganese superoxide dismutase (MnSOD) in mitochondria, inflammation (tumor necrosis factor α and interleukin 1β), increased accumulation of NF-κB in nuclear fraction, p53 induction, and apoptotic cell death (caspase 3 activity and DNA fragmentation). Treatment of mice with EGCG markedly attenuated cisplatin induced mitochondrial oxidative/nitrative stress, mitochondrial damages to electron transport chain activities and antioxidant defense enzyme activities in mitochondria. These mitochondrial modulations by EGCG led to protection mechanism against cisplatin induced inflammation and apoptotic cell death in mice kidney. As a result, EGCG improved renal function in cisplatin mediated kidney damage. In addition to that, EGCG attenuated cisplatin induced apoptotic cell death and mitochondrial reactive oxygen species (ROS) generation in human kidney tubular cell line HK-2. Thus, our data suggest that EGCG may represent new promising adjunct candidate for cisplatin.     

The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C

Diazinon is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programs. Reactive oxygen species (ROS) caused by OPIs may be involved in the toxicity of various pesticides. The aim of this study was to investigate how diazinon affects lipid peroxidation (LPO) and the antioxidant defense system in vivo and the possible ameliorating role of vitamins E and C. For this purpose, experiments were done to study the effects of DI on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in adult rat heart. Experimental groups were: (1) control group, (2) diazinon treated (DI) group, (3) DI+vitamins E and C-treated (DI+Vit) group. The levels of malondialdehyde (MDA) and the activities of SOD and CAT increased significantly in the DI group compared with the control group. The activity of SOD and the levels of MDA decreased significantly in the DI+Vit group compared with the DI group. The differences between the DI+Vit and control groups according to the MDA levels and the activities of both SOD and CAT were statistically significant. These results suggest that treating rats with a single dose of diazinon increases LPO and some antioxidant enzyme activities in the rat myocardium and, in addition, that single-dose treatment with a combination of vitamins E and C after the administration of diazinon can reduce LPO caused by diazinon, though this treatment was not sufficiently effective to reduce the values to those in control group.