Hepatic and renal damage induced by oxidative stress are improved by administration of enalapril and nicorandil in diabetic rats

Oxidative stress plays a crucial role in tissue damage occurring in diabetes mellitus [DM]. A number of studies reported that antioxidants can attenuate the complications of DM. The present work was undertaken to study the histopathological and biochemical effects of oxidative stress on hepatic and renal tissue in streptozotocin-induced DM in rats, and to evaluate the role of enalapril and nicorandil and their combination in combating oxidative stress-induced pathological effects. Diabetic rats were divided into groups of six rats and received 10mgkg, intraperitoneally of enalapril [an angiotensin-converting enzyme [ACE] inhibitor that is used in the treatment of hypertension], 10lmg/kg, orally of nicorandil [a potassium channel opener which is effective in the treatment of hypertension and angina pectoris] and their combination once daily for one month. Analysis of plasma and tissue parameters of oxidative stress was done. In addition, specimens were taken from the liver and kidney for histopathological examination. Plasma of diabetic rats showed significant elevation of glucose level and alteration in oxidative stress parameters, Cytochernical studies on hepatic and renal tissues showed altered levels of oxidative stress parameters. Histopathological examination of hepatic and renal specimens showed degenerative changes. Treatments of the diabetic rats with enalapril, nicorandil and their combination led,to improvement of the abnormalities in oxidative stress parameters and also in the histopathological abnormalities of the liver may be and kidney. These results indicate that oxidative stress an important cause of the structural damage occurring in many organs in DM, even in early stages of the disease. The antioxidant activities of enalapril, nicorandil and their combination may play an important role in protection against oxidative stress in DM

Deterioration of testicular functions in adult male rabbit after exposure to mobile phone radiation with impending recovery

The accumulate effects of electromagnetic field [EMF] release from mobile phones have many effects on multiple organs. Nevertheless, its effect on testicular function is still debated. The objective of the study is to clarify the alterations in testicular functions after exposure to electromagnetic radiation of mobile phone and to investigate the possibility of recovery. Eighteen adult male rabbits are enrolled into 3 groups: control, exposed and recovery group. Tine exposed and recovery groups are exposed to mobile phones in standby position for 18 hours /day and six day/week for 14 weeks. After that, the recovery group was monitored for another 14 weeks. exposure to EMR induced a significant drop in sperm count, sperm motility and sperm fast forward motility at the 6[th], 12[th] and 9[th] week respectively and get maximum inhibition at the 14[th] week. These finding were concomitant with degenerative changes in seminiferous tubules and interstitial cells of Leydig. These negative effects may be attributed to the detectable decrease in the serum level of testosterone, gonadotophic hormones, increase the level of oxidative stress and direct deterioration of testicular tissue. The other study points [body and testicular weight, body temperature and percentage of sperm morphology and live sperm] did not show any alteration. Recovery period significantly ameliorated the suppressed testicular functions and also, restored the hormonal and oxidative biomarkers within the 14 weeks. the longitudinal exposure to EMR causes testicular dysfunction that may be mediated by hormonal disturbances, oxidative stress or direct damage on testicular tissue that could reverse and improve within the recovery period

Role of allium sativum in the protection against oxidative stress and associated biochemical changes in streptozotocin-induced diabetes in rats

Oxidative stress is involved in both pathogenesis and complications of diabetes. The need to identify agents with a potential for preventing such damage and complication has assumed great importance. The present study was devoted to the assessment of the effect of chronic oral administration of raw garlic homogenate on oxidative stress and associated biochemical changes in streptozotocin [STZ]-induced diabetic rats. Male Sprague- Dawley rats weighing 180-200 g were used. Rats were divided into four groups 6 rats each. Group 1: is a control group in which rats received only 0.5 ml of vehicle [citrate buffer pH 4.5] as a single intraperitoneal [i.p.] dose. Group II: in which rats were treated orally with 20% raw garlic homogenate in distilled water in a dose of 500 mg/kg once a day for 30 days. Group III: rats were treated with 0.5 ml 2.4% solution STZ in citrate buffer in a single i.p. dose of 60 mg/kg. Group IV: rats were treated with 0.5 ml 2.4% solution STZ in citrate buffer in a single i.p. dose of 60 mg/kg, plus orally with 20% raw garlic homogenate in distilled water in a dose of 500 mg/kg once a day for 30 days. Blood aliquots were collected for serum separation. Serum levels of glucose, aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], bilirubin, urea and creatinine as well as total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides were evaluated. HDL-cholesterol was also determined. The animals were then sacrificed and specimens were taken from the liver and kidney tissues and tissue homogenates were separated for determination of oxidative stress and antioxidant parameters such as malondialdehyde [MDA], reduced glutathione [GSH] and catalase [CAT] levels. Chronic oral administration of raw garlic homogenate produced a significant reduction in the serum levels of glucose[P<0.01], AST [P<0.05], ALT[P<0.05], ALP [P<0.05], bilirubin [P<0.01], urea [P<0.01] and creatinine [P<0.05] in STZ-induced diabetic rats. Furthermore,there was a significant decrease in total serum cholesterol [P<0.05], LDL-cholesterol [P<0.01], VLDL-cholesterol [P<0.05], and triglycerides [P<0.05] and a significant increase in HDL-cholesterol [P<0.01] as compared to STZ -induced diabetic group. On the other hand, hepatic and renal MDA were significantly reduced, [P<0.01] and [P<0.05], respectively. Also, there was a significant increase in both hepatic [P<0.01] and renal [P<0.05] GSH levels and catalase activity [P<0.001] as compared to STZ-induced diabetic rats. Chronic oral administration of raw garlic homogenate attenuates oxidative stress and associated biochemical changes in STZ-induced diabetic rats

Role of copper complexes in the protection against stress-induced gastric ulcer in rats

Copper complexes achieve an anti-ulcer activity, several investigations were submitted to clarify the possible mode of action of these copper complexes as potent anti-ulcer drugs. These agents have a wide range of pharmacological activities that could be explained on the basis of the activation of copper dependant enzymes and their physiochemical properties. Copper complexes are reported to have potent anti-inflammatory and anti-ulcer effects. All of these copper complexes were found to be more active than either inorganic copper salts or their parent completing agents, Copper complexes were effective in reducing ulcer number as well as ulcer severity, they have an antisecretory activity. To further clarify this point, the present study was conducted to evaluate anti-ulcer activity of two types of copper complexes which are: Cu [l]-[nicotinic acid][2]Cl complex and Cu[II] [glycinate][2] complexe and their combination in water immersion-restraint stressed [WIRS] ulcer rat model. The present study was conducted on 25 mule Wister albino rats, that were randomly divided info three groups:Group I: Control non-stressed group: in which animals were received only an intragastric dose of 0, 5ml of vehicle [0.25% Tween -80 in saline solution]. Group II: Non-pretreated WIRS group; in which rats were subjected to restraining by WIRS and received an intragastric dose of 0.5ml of vehicle. Group III: Treated WIRS groups: in which rats were subjected to restraining and subdivided according to the received drug into: Subgroup A: received an intragastric dose of 8 mg/kg body mass Cu[I]-[nicotinic acid][2]Cl complex, in 0.5ml of vehicle immediately prior to stress. Subgroup B: received an intragastric dose of 5 mg/kg body mass Cu[II][glycinate]2 complex, in 0.5ml of vehicle immediately prior to stress. Subgroup C: received an intragastric dose of 5 mg/kg body mass Cu[II] [glycinate][2] complex + 8 mg/kg body mass Cu[T]-[nicotinic acid][2]CI complex, in 0.5 ml of vehicle immediately prior to stress.Group II and III were subjected to restraining by fixing I he four limbs to a metal board, and placed in a water bath maintained to the level of the xiphoid process at a temperature of 23 +/- 1 °C for 3 to 5 hours.Blood samples were taken from all groups as plasma for determination of total superoxide dismutase [SOD] activity or serum for determination of total nitrite level. After withdrawal of the blood samples, their stomachs were removed and opened along the greater curvature. All the stomachs were formalin fixed and paraffin embedded, for assessment of histopathological changes affecting these structures using light microscopical examination. Administration of intragastric copper complexes increased plasma level of SOD from 0.54 +/- 0.02 unit/ml and 0.32 +/- 0.63 unit/ml for control non-stressed group and non-pretreated WIRS group to 0.84+0.10 unit/ml 1.39 +/- 0.15 unit/ml and 2.27 +/- 0.13 unit/ml for Cu[I]-[nicotinic acid][2]Cl complex, Cu[II][glycinate][2] complex and combination of two types of copper complexes, respectively. In the other hand, WIRS was associated with a significant increase in total serum nitrite level with a mean of 70.11 +/- 6.12 micro mol/1 in a comparison with non stressed group [32.09 +/- 2.05 micro mol/l]. Pretreatment of WIRS animals with both types of copper complexes; Cu[I]-[nicotinic acid][2]Cl complex and Cu[Il] [glycinate][2] complex and their combinations intragastrically did not produce a significant reduction of nitrite level, compared to WIRS group, with means 59 +/- 1.90 micro mol/L, 64.93 +/- 2.66pmol/L and 63.20+1.78 micro mol/L for both [Cu[l]-[nicotinic acid][2]Cl complex and Cu[II] [glycinate][2] complex and their combined mixture respectively. The histopathological findings of the light microscopical examination demonstrated that there was no microscopic abnormality in the gastric mucosae in the non-stressed control group [group I]. Moderate to severe gastric erosion was seen in the examined cases, with denudation of parts of the gastric mucosae of different thickness. A complete gastric ulceration with complete necrosis of parts of the gastric mucosaeseen in the most severe forms of non-pretreated WIRS group [group II]. Either no histopathologic abnormality or mild erosion was seen in WIRS groups treated with Cu[I]-[nicotinic acid][2]Cl, Cu[II][glycinate]2 complexes and their combined mixture [group III], From these results It can be concluded that both intragastrically injected copper complexes and their combined mixture exerted protective effect on the gastric mucosa of WIRS induced ulcer in rats. This is confirmed by the incosistantly measured biochemical parameters [plasma SOD and serum nitrite levels] and the histopathological examination of the gastric mucosa

Protective effects of oleanolic acid and vitamine E on thyroid dysfunction and lipid peroxidation in cadmium- induced toxicity in rats

The effect of oleanolic acid or vit. E on heavy metal [cadmium] -induced thyroid dysfunction and lipid peroxidation in male rats was studied. The animals divided into 3 groups each of which 6 rats. The first group were injected with 1mg/kg/day cadmium chloride, 1% solution in distilled water subcutaneously daily for 30 days. The second group were injected simultaneously with equivalent dose of cadmium chloride [1mg/kg/day] subcutaneously and oleanolic acid in a dose of 5 mg/kg/day, 2% suspension in 2% tween 80 intramuscularly for 30 days. The third group were injected simultaneously with equivalent dose of cadmium chloride [1mg/kg/day] subcutaneously and vit. E, in a dose of 100mg/kg [5% solution in saline] intramuscularly for 30 days. The control groups were divided into 3 groups. The first group was treated with distilled water, the second one was treated with tween 80 and lastly the third group was trated with saline. Cadmium chloride treatment alone led to decrease in concentrations of serum thyroid hormones, zinc and copper concentration [p<0.01]. In addition, a significant increase in both malondialdyhyde [MDA] levels and thyroid stimulating hormone [TSH] has been observed by Cd-treatment alone [p<0.01]. Treatment with either oleanolic acid or vit.E improved the metal-induced decrease in serum thyroid function. Treatment with oleanolic acid lead to decrease in levels of blood and hepatic malondialdyhyde but remain higher than normal rates [47.14 +/- 0.82 micro mol/L and 119 +/- 0.86 micro mol/g wet tissue, respectively]. However, treatment with Cd and vit. E restored blood and hepatic malondialdyhyde levels toward normal values [34.7 +/- 0.65 micro mol/L and 100.4 +/- 1.44 micro mol/g wet tissue, respectively]. The effect of vit. E combined with cadmium is significant compared with the effect of oleanolic acid treatment with cadmium [p<0.01]. The protective effect of each oleanolic acid or vit. E against cadmium-induced thyroid dysfunction is mediated through its antioxidative action

Role of oxidative stress in cisplatin - induced nephrotoxicity in rats

Cisplatin [cis diammine dichloroplatinum] is a potent antitumor drug. Expansion of the clinical utility of cisplatin has been limited by its toxicity where acute and chronic forms of renal injury have been described due to apoptosis. The mechanism by which it activates the myriad of apoptotic pathways remains unclear. Several studies have now documented the importance of reactive oxygen metabolites [ROM] in cisplatin-induced renal cell apoptosis. To further clarify this point the present study was conducted to evaluate the oxidative stress induced by cisplatin. Rats were treated either by high single intraperiotoneal dose [7mg/kg] or by repeated small doses [4mg/kg] twice weekly for one month. Rats were sacrificed by decapitation after 48 hours of high dose intake or 24 hours after intake repeated small doses. Kidney tissues were removed for histopathological examination, after homogenization these tissues were removed for determination of glutathione [GSH]. Blood samples were taken from rats for determination of serum level of creatinine, blood urea nitrogen [BUN] and nitric oxide [NO]. Histopathological examination of kidney tissue revealed degenerative changes with tubular change, especially in the proximal convoluted tubules. Significant elevation in serum creatinine [2.24 +/- 0.18 vs 2.12 +/- 0.18] and BUN [146 +/- 10.6 vs132 +/- 11.2] levels were observed. Administration of cisplatin in large dose or small repeated doses causes significant elevation in serum [NO] level [10.4 +/- 0.8 micro mol/l and 9 +/- 0.53 micro mol/l respectively] as well as depletion in renal [GSH] tissue levels [1.02 +/- 0.09 micro mol/l w.wt wet, weight] and 1.12 +/- 0.08 micro mol/g w.wt, respectively]. From these results, it can be concluded that single high dose or small repeated doses of cisplatin-induced nephrotoxicity was associated with induction of oxidative stress. Use of antioxidants in conjunction with cisplatin could be a value in minimizing its toxicity