Effect of Curcumin on Cisplatin- and Oxaliplatin-Induced Oxidative Stress in Human Embryonic Kidney (HEK) 293 Cells

Generation of reactive oxygen species (ROS) is involved in the nephrotoxicity of platinum anticancer drugs. This study involved incubation of human embryonic kidney (HEK) 293 cells in cell culture media supplemented with cisplatin or oxaliplatin in the presence or absence of curcumin, a well-studied antioxidant. Thereafter several indices of oxidative stress have been measured, which included glutathione (GSH), total antioxidant capacity (TAC), and antioxidant enzymes [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX)]. The impact of platinum drugs on cells viability, lipid peroxidation, and lactate dehydrogenase leakage was also examined. The results show that at both acute (60 min) and chronic (24 h) durations of incubation, cisplatin and oxaliplatin induced oxidative stress as evidenced by significant inhibition of the activities of SOD, CAT, and GPX enzymes as well as significant reduction of the concentrations of GSH and TAC. Curcumin ameliorated the oxidative stress induced by these insults by significantly restoring the measured oxidative indices. Our findings provide evidence that curcumin significantly ameliorates oxidative stress induced by both cisplatin and oxaliplatin in HEK cells.     

Beneficial effects of aminoguanidine on radiotherapy‐induced kidney and testis injury

This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine (AG), on radiotherapy (RT)‐induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+RT and (v) RT+AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total oxidant status (TOS), total antioxidant capacity, oxidative stress index (OSI), blood urea nitrogen (BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT‐treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT‐treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT‐treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT‐induced kidney and testis injury.     

Altered antioxidant capacity in human renal cell carcinoma: role of glutathione associated enzymes

PURPOSE: We aimed to discern the role of glutathione (GSH) associated enzymes in maintaining high GSH levels in renal cell carcinoma (RCC) of the clear cell type and analyze RCC enzyme antioxidant capacity. Since changes in cellular redox balance in RCC might also be related to alterations of glutathione S-transferase (GST) phenotype, GST class alpha and pi expression was also explored. METHODS AND MATERIALS: Human kidney specimens of tumor and distant nontumor regions were obtained from 15 patients with RCC at the time of surgery. The activities of GSH-replenishing enzymes, gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transferase (gamma-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST alpha and pi class expression was determined by immunoblot. RESULTS: In the course of renal cancerization, significant changes appear in the activities of GSH-replenishing and antioxidant enzymes. The activity of the key enzyme of GSH synthesis, gamma-GCS, is up-regulated (P < 0.001), while the activities of gamma-GT and GR are down-regulated in renal tumors compared to nontumor tissue (P < 0.001 and P < 0.05, respectively). Activities of GPX and CAT were also down-regulated (P < 0.001 and P < 0.05, respectively) in RCC. Changes in enzyme antioxidant capacity in RCC were associated with decreased GST class alpha (P < 0.001) and unchanged GST pi expression at the protein level. CONCLUSIONS: Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST alpha expression, may be important factors in development and tumor growth. The up-regulation of gamma-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress.     

Glutathione S-transferase-P1 expression correlates with increased antioxidant capacity in transitional cell carcinoma of the urinary bladder

OBJECTIVES: Our aim was to perform a comprehensive analysis of the antioxidant capacity of transitional cell carcinoma (TCC) of urinary bladder and discern the role of enzymes associated with glutathione (GSH) in maintaining high GSH levels in these tumours. Because the redox-sensitive protein glutathione S-transferase P1 (GSTP1) might provide an important link between high antioxidant capacity and inhibition of apoptotic pathways, we also explored how the redox state in tumour cells interacts with the expression of GSTP1. METHODS: We examined spectrophotometrically the specific activities of GSH-replenishing enzymes involved in GSH synthesis (gamma-glutamylcysteine synthetase, gamma-GCS), GSH regeneration (glutathione reductase, GR), and antioxidant protection (glutathione peroxidase, GPX; superoxide dismutase, SOD) in the cytosolic fraction of tumours and the surrounding normal tissue of 30 TCC patients. GSTP1-1 expression was also analyzed. RESULTS: We found a significant increase in the activity of both GSH-replenishing and antioxidant enzymes as well as enhanced GSTP1-1 expression in tumours in comparison with adjacent normal uroepithelium. Mean gamma-GCS and GR activities in tumours were about 4- and 2-fold higher, respectively, than in corresponding normal tissue. Expression of GSTP1 correlated significantly with GSH level and gamma-GCS and GR activities. GPX and SOD activities in TCC were also markedly increased. CONCLUSIONS: Enhanced GSH-replenishing pathways account for increased GSH levels in TCC. Upregulated GPX and SOD also contribute to high antioxidant potential in TCC. Under such conditions, expression of redox-sensitive GSTP1 protein is upregulated.     

Iron and oxidative stress in renal insufficiency

BACKGROUND/AIMS: Iron (Fe) can cause tissue injury and oxidative stress by catalyzing hydroxyl radical production and lipid peroxidation. Intravenous (i.v.) Fe preparations are routinely administered to treat anemia in patients with chronic renal failure (CRF), a condition marked by oxidative stress and inflammation. In an earlier study, we showed that iron overload augments oxidative stress in the cardiovascular tissues of CRF rats. This study was designed to expand these observations to other major organs. METHODS: Rats were randomized into CRF (5/6 nephrectomized) and sham-operated control (CTL) groups. Each group was subdivided into Fe-loaded (single i.v. injection of iron dextran complex, 0.5 g/kg) and placebo-treated subgroups. After 13 weeks, systolic blood pressure, blood hemoglobin (Hb), plasma Fe concentration, lipid peroxidation products, superoxide generating enzyme, NAD(P)H oxidase, and antioxidant enzymes were determined. RESULTS: Systolic blood pressure was equally elevated and creatinine clearance was equally reduced in both CRF groups. Fe administration raised Hb, serum Fe and transferrin saturation in both CRF and CTL groups. The plasma concentration of lipid peroxidation product, malondialdehyde, was increased by Fe injection in CRF rats but not the control group. Renal tissue abundance of gp91(phox) subunit of NAD(P)H oxidase was elevated in the untreated CRF group and was partially reduced in the iron dextran-treated CRF group. Tissue abundance of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were decreased in both untreated and iron dextran-treated CRF groups. CONCLUSION: CRF resulted in marked SOD, CAT and GPX deficiencies. A single i.v. administration of iron dextran in rats with CRF induced oxidative stress as measured by increased lipid peroxidation products and decreases in antioxidant enzymes.     

Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.     

Time course of antioxidant enzyme activities in liver transplant recipients

Reactive oxygen species (ROS) play a central role in ischemia-reperfusion injury after organ transplantation. They are degraded by endogenous radical scavengers such as antioxidant enzymes. The purpose of this study was to evaluate the temporal variations of antioxidant enzyme activities in liver transplant recipients. The study was performed in 13 liver transplant patients (11 men and 2 women). Blood samples were obtained pre- and postsurgical intervention: before transplant (T(0)), and 1, 6, 12, 24, 48, and 72 hours, as well as 5 and 7 days thereafter. We determined total and specific superoxide dismutase (SOD) activity, catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) activities as well as malondialdehyde (MDA) and low-density lipoproteins (LDL). The results showed increased SOD and mainly GPX activities after liver transplantation, which correlated with MDA levels. Total SOD activity was mainly represented by Mn-SOD (75%) and Cu,Zn-SOD (25%), whereas Fe-SOD was not detected. In conclusion, the enhanced antioxidant enzyme activities reported in this study indicated a control of oxidative stress generated in liver transplantation. In this sense, although MDA levels showed an enormeous increase at 1 hour after transplantation, the lipid peroxidation was compensated for by GPX activity.     

Superoxide dismutase,catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension

BACKGROUND: Earlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (.OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative stress in animals with lead-induced HTN is associated with dysregulation of the main antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) or increased superoxide producing enzyme nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H]. METHODS: Male Sprague-Dawley rats were randomly assigned to lead-exposed and control groups. Animals in the lead-exposed group were provided with drinking water containing 100 ppm lead acetate for 12 weeks. The control group was provided with regular drinking water. At the conclusion of the experiment, immunodetectable Cu Zn SOD, Mn SOD, CAT, GPX and gp91 phox subunit of NAD(P)H oxidase were determined by Western analysis in the kidney, brain and left ventricle of control and lead-exposed rats. Subgroups of the study animals were treated with IV infusion (180 micromol/kg/h) of the superoxide trapping agent, tempol, and arterial pressure and urinary nitric oxide (NO) metabolite (NOx) excretion were determined. RESULTS: Lead exposure for 12 weeks resulted in a marked rise in systolic blood pressure, a significant reduction in urinary NOx excretion, a significant increase in kidney and brain Cu, Zn SOD, a significant increase in brain and insignificant increase in kidney and heart gp91 phox. In contrast, Mn SOD, CAT and GPX in the kidney, brain and left ventricle were unchanged. Incubation with lead acetate did not alter SOD activity in vitro. Infusion of tempol significantly lowered arterial pressure and raised urinary NOx excretion in the lead-exposed group (but had no effect in the control group) pointing to increased superoxide production in the lead-exposed animals. CONCLUSION: Animals with lead-induced hypertension exhibited oxidative stress which was associated with mild up-regulation of superoxide-generating enzyme, NAD(P)H oxidase, with no evidence of quantitative SOD, CAT or GPX deficiencies.     

Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study

Atherosclerotic cardiovascular disease is the most frequent cause of death in patients with end-stage renal disease who have undergone dialysis treatment. Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant systems may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of this study was to investigate the influence of a vitamin E-coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients. In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd month of the study, and 10 weeks after the interruption of the use of vitamin E-coated dialyzer. All HD patients were treated by erythropoietin (EPO) and received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37 micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten-week interruption of the use of the vitamin E-coated dialyzer led to near initial values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters. Statistical analysis of results was performed by conventional methods and analysis of variance. The findings of the current study confirm the beneficial effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.     

Lycopene inhibits caspase-3 activity and reduces oxidative organ damage in a rat model of thermal injury

Oxidative stress has been implicated in various pathological processes including burn induced multiple organ damage. This study investigated the effects of lycopene treatment against oxidative injury in rats with thermal trauma. Under ether anesthesia, shaved dorsum of the rats was exposed to 90°C bath for 10s to induce burn and treated either vehicle (olive oil) or lycopene (50mg/kg orally). Rats were decapitated 48 h after injury and the tissue samples from lung and kidney were taken for histological analysis and the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and caspase-3 activities. Proinflammatory cytokines, TNF-α and IL-1β, were assayed in blood samples. Severe skin scald injury caused a significant decrease in GSH levels, SOD and CAT activities, and significant increases in MDA levels, MPO and caspase-3 activities of tissues. Similarly, plasma TNF-α and IL-1β were elevated in the burn group as compared to the control group. Lycopene treatment reversed all these biochemical indices. According to the findings of the present study, lycopene possesses antiinflammatory, antiapoptotic and antioxidant effects that prevents burn-induced oxidative damage in remote organs.     

Effects of Aulosira fertilisima against Cisplatin-Induced Nephrotoxicity and Oxidative Stress in Rats

Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidence suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Aulosira fertilisima Ghose (EEA) was evaluated using cisplatin (5 mg/kg^?1 i.p.)-induced renal damage in rats. EEA showed higher significant effect on DPPH radical scavenging activity as compared with methanol extract of A. fertilisima (MEA) and water extract of A. fertilisima (WEA). Thus, EEA was selected for further in vivo studies. The serum urea and creatinine levels in the cisplatin alone-treated group were significantly elevated with respect to normal group of animals. The levels were reduced in the EEA (100 mg/kg, p.o) plus cisplatin-treated groups. Renal oxidative stress was determined by renal TBARS, CD and reduced glutathione levels, and by enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin-produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the study indicated that A. fertilisima significantly and dose-dependently protected the nephrotoxicity induced by cisplatin. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.     

Evaluation of renoprotective effect of Aphanizomenon flos-aquae on cisplatin-induced renal dysfunction in rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidence has implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Aphanizomenon flos-aquae (AFA), blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of AFA against cisplatin-induced oxidative stress and renal dysfunction. The ethanolic extract of Aphanizomenon flos-aquae (EEAFA) (25, 50, 100 mg/kg(-1) p.o.) was administered two days before through three days after cisplatin challenge (5 mg/kg(-1) i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEAFA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of AFA in cisplatin-induced nephrotoxicity.     

Evaluation of Renoprotective Effect of Aphanizomenon flos-aquae on Cisplatin-Induced Renal Dysfunction in Rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidence has implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Aphanizomenon flos-aquae (AFA), blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of AFA against cisplatin-induced oxidative stress and renal dysfunction. The ethanolic extract of Aphanizomenon flos-aquae (EEAFA) (25, 50, 100 mg/kg^?1 p.o.) was administered two days before through three days after cisplatin challenge (5 mg/kg^?1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEAFA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of AFA in cisplatin-induced nephrotoxicity.     

Protective effects of gallic acid against methotrexate-induced toxicity in rats

Background: Methotrexate, as a chemotherapy drug, can cause chronic liver damage and oxidative stress. Aim of this study was to evaluate the preventive effect of gallic acid (GA) on methotrexate (MTX)-induced oxidative stress in rat liver.

Methods: Twenty-eight male rats were randomly divided into four groups as control, MTX (20?mg/kg, i.p.), MTX?+?GA (30?mg/kg/day, orally) and GA treated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. Malondialdehyde (MDA) and glutathione (GSH) levels and hepatic antioxidant enzymes activities including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed in liver tissue. The expression of SOD2 and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was evaluated by light microscopy.

Results: The result obtained from current study showed that GA remarkably reduced MTX-induced elevation of AST, ALT and ALP and increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well as GPx1 and SOD2 gene expressions. Histological results showed that MTX led to liver damage and GA could improve histological changes.

Conclusions: Our results indicate that GA ameliorates biochemical and oxidative stress parameters in the liver of rats exposed to MTX.     

Influence Of Chronic Exercise On Red Cell Antioxidant Defense,Plasma Malondialdehyde And Total Antioxidant Capacity In Hypercholesterolemic Rabbits

Despite the knowledge on the antiatherogenic effects of exercise, the mechanism by which exercise reduces atherogenic risk remains unknown. In this study, we investigated the hypothesis that chronic exercise-induced oxidative stress may increase plasma total antioxidant capacity and antioxidant defense in the red cells. For 8 weeks, 60 male Dutch rabbits were fed rabbit chow with or without the addition of 2% cholesterol. The animals were further divided into rest and exercise groups (n = 15 for each group). Animals in exercise groups ran on a rodent treadmill at 15 m/min for 10 to 60 minutes gradually for 5 days per week for a total of 8 weeks. At the end of experiments, blood samples were collected and glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) activities were determined in red blood cells. Total antioxidant capacity (TAC), malondialdehyde (MDA) and total thiol (T-SH) levels were measured in plasma. Thoracic aorta and carotid arteries were isolated for histological examination to evaluate atherosclerosis. Eight weeks of chronic exercise reduced atherogenic diet-induced atherosclerotic lesions in all the arteries studied, along with positive changes in cholesterol profile, especially increase of serum HDL-C level. Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both control and hypercholesterolemic diet groups. Erythrocyte catalase activity was significantly increased by chronic exercise (p < 0.05), whereas total SOD activity rose with exercise only in the control group. Surprisingly, GPX activity was significantly reduced (P < 0.05) in response to exercise in the control group and also in the high cholesterol diet group. Exercise is a useful tool for the prevention and regression of atherosclerosis which is evident by our findings of the enhancement of plasma TAC and positive change in serum cholesterol profile. However, the effect of exercise on red cell antioxidant activities is limited in the hypercholesterolemic animals compared to control animals, possibly in part because of alterations in the ability to adapt to exercise-induced oxidative stress in high cholesterol diet.

Key Points

• Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both control and high cholesterol diet groups.
• GPX activity was significantly reduced in response to exercise in the control group and also in the high cholesterol diet group.
• Eight weeks of chronic exercise reduced atherogenic diet-induced atherosclerotic lesions in all the arteries studied.

Key words: Chronic exercise, antioxidant, malondialdehyde, thiol, atherosclerosis     

Increased oxidative stress and oxidative damage associated with chronic bacterial prostatitis

目的:探讨慢性细菌性前列腺炎是否会在患者体内引起氧化应激加剧和氧化损伤及其可能的机理。方法:采用病例对照研究设计,用分光光度分析法检测了随机纳入的70例慢性细菌性前列腺炎患者(CBPP)与70例健康成人志愿者(HAV)的血浆一氧化氮(NO),维生素 C(VC)、维生素 E(VE)和β-胡萝卜素(β-CAR)水平以及红细胞丙二醛(MDA)水平,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPX)活性。结果:与 HAV 组相比较,CBPP 组的血浆 NO 和红细胞 MDA 的均值显著增高(P<0.001),血浆 VC、VE 和β-CAR 及红细胞 SOD、CAT 和 GPX 活性均值显著降低(P<0.001)。70例 CBPP 的偏相关分析结果提示,随着病程的延长,NO 和 MDA 值逐渐增高(P<0.001),VC、VE、β-CAR、SOD、CAT 和 GPX 值逐渐降低(P<0.05-0.001)。70例 CBPP 的逐步回归提示其模型为 Y=-13.2077 0.1894MDA 0.0415NO-0.1999GPX,F=18.2047,P<0.001,r=0.6729,P<0.001。结论:本研究结果提示,患者体内存在着由慢性细菌性前列腺炎引起的氧化应激加剧和氧化损伤,且这种现象与患者的病程密切相关。     

Carotid artery intima-media thickness correlates with oxidative stress in chronic haemodialysis patients with accelerated atherosclerosis.

BACKGROUND: Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). Increased oxidative stress might be the major factor leading to high cardiovascular mortality rate in HD patients. The aim of our study was to clarify effects of uraemia and dialysis on oxidative stress parameters and explore the relation between oxidative stress markers and carotid artery intima-media thickness (CIMT) as an indicator of atherosclerosis. METHODS: Twenty chronic HD patients, 20 predialytic uraemic patients and 20 healthy subjects were included in the study. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. RESULTS: Both chronic HD and predialytic uraemic patients had enhanced oxidative stress indicated by higher levels of nitrite/nitrate, TBARS and PCO, and lower levels of P-SH, SOD, CAT and GPx compared to controls. HD patients had significantly higher CIMT and nitrite/nitrate while significantly lower P-SH,vitamin E, SOD, CAT and GPx compared to predialytic uraemic patients. There was a significant positive correlation between CIMT and TBARS (r = 0.38, P = 0.003) and nitrite/nitrate levels (r = 0.41, P = 0.001), while there was a significant negative correlation between CIMT and SOD (r = -0.35, P = 0.01), CAT (r = -0.65, P < 0.001) and P-SH levels (r = -0.50, P < 0.001). A linear regression analysis showed that TBARS were still significantly and positively correlated with CIMT (P = 0.001), while CAT and P-SH were significantly and negatively correlated with CIMT (P = 0.002 and P = 0.048, respectively). CONCLUSIONS: HD exacerbates oxidative stress and disturbances in antioxidant enzymes in uraemic patients. We propose that serum TBARS and nitrite/nitrate can be used as positive determinants, while erythrocyte SOD, CAT and P-SH may be used as negative determinants of atherosclerosis assessed by CIMT in uraemic and HD patients.     

Evaluation of protective effects of gallic acid on cisplatin-induced testicular and epididymal damage

Cisplatin is an effective chemotherapeutic drug used to treat many types of tumours. However, it may cause male reproductive toxicity. Gallic acid exhibits beneficial effects such as antioxidant, anti-inflammatory and antitumor. The current study investigated the beneficial effects of gallic acid against testis and epididymis toxicity induced by cisplatin. Male rats were divided into 4 groups as follows (n = 7): Control, cisplatin (a single dose of 8 mg/kg), Gallic acid (50 mg/kg) and cisplatin +Gallic acid groups. Testis was examined morphometrically by stereological methods. In addition, apoptosis, DNA damage, oxidative stress parameters in testis and testosterone in serum were measured. Epididymis was histopathologically evaluated. As a result, a significant decrease was observed in the number of spermatogonia, Leydig and Sertoli cells, testicular volume, height of germinal epithelial, Bcl-2 immunopositive cell number, activity of CAT, GSH and SOD enzymes and serum testosterone levels compared with the cisplatin group control group, while a significant increase was observed in the number of Caspase-3, Bax and 8-OHdG immunopositive cells and the MDA levels. However, Gallic acid significantly restored these parameters. Our study reveals that Gallic acid may improve Cisplatin-induced male reproductive toxicity by reducing oxidative stress, suppressing apoptosis and DNA damage and restoring structural and functional deterioration.     

The effect of dehydroepiandrosterone on renal ischemia-reperfusion-induced oxidative stress in rabbits

Reactive oxygen species (ROS) can play an important role in the pathogenesis of ischemia-reperfusion (I/R) injury. Dehydroepiandrosterone (DHEA) is one of the hormones secreted from adrenal glands, and in some studies it has been shown that DHEA has antioxidant properties. This experimental study was designed to determine the effect of DHEA on I/R-induced oxidative stress in rabbit kidney. Twenty-one rabbits were divided into three groups. Rabbits were subjected to 60 min of left renal pedicle occlusion followed by 24 h of reperfusion. DHEA (50 mg/kg) (I/R + DHEA group) or equal volume of vehicle (I/R group) was administered 3 h prior to ischemia. The control group received only laparotomy without I/R, DHEA or vehicle. At the end of the reperfusion periods, rabbits were decapitated. Renal tissues were taken for determination of malondialdehyde (MDA) levels as an indicator of lipid peroxidation and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities as antioxidant enzymes. In the I/R group, while renal SOD and CAT activities were significantly lower, MDA levels were significantly higher than in the I/R + DHEA group and controls. In the I/R + DHEA group, enzyme activities and MDA levels were similar to the controls. There was no significant difference in terms of renal GPX activity among the groups. DHEA may have a beneficial effect on renal tissue against oxidative damage due to I/R by preventing decreases in some antioxidant enzyme activities.     

Potential of morin and hesperidin in the prevention of cisplatin-induced nephrotoxicity

Oxidative stress is one of the important mechanisms of cisplatin-induced nephrotoxicity. Therefore, this study was designed to explore the potential protective effects of morin and/or hesperidin on oxidative stress in cisplatin-induced nephrotoxicity. This study was performed on 42 Wistar rats. Rats were divided into seven groups: control, morin, hesperidin, cisplatin, cisplatin?+?morin, cisplatin?+?hesperidin, and cisplatin?+?morin?+?hesperidin. Morin and/or hesperidin were given for 10 consecutive days by oral gavage and on the 4th day a single dose of cisplatin (7?mg/kg) was injected intraperitoneally. After administrations, on the 11th day of the experiment the animals were killed, and malondialdehyde (MDA), nitric oxide (NOx), glutathione (GSH) levels and myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD) activity were measured. Cisplatin-treated rats showed increased levels of MDA, and decreased levels of NOx also activity of CAT. Morin and/or hesperidin pretreatment prevent oxidative stress in kidney tissue, while they increase the NOx level, CAT activity, and decrease MPO activity. In conclusion, morin?+?hesperidin pretreatment may have a significant potential for protection of cisplatin-induced nephrotoxicity.