Effects of reduced glutathion and vitamin c on cisplatin-induced hepatotoxicity in rats

Cisplatin [CDDP] is a widely used anticancer drug, however it can produce undesirable side effects such as hepatotoxicity when used at high doses. The aim of the present work to evaluate the protective effect of reduced glutathione [GSH] and vitamin C on CDDP-induced hepatotoxicity. Eighty male Sprague-Dawley rats were divided into eight groups, 10 rats each. Group I, control group. Group II received Cisplatin [7.5 mg /kg, i.p] for 5 consecutive days. Group III received GSH [600 mg/kg /day, i.p]. Group IV received vitamin C [250 mg/kg/day, orally]. Group V received GSH for 15 days then CDDP for 5 days. Group VI administered vitamin C for 15 days then CDDP for 5 days. Group VII administered both GSH and CDDP for 5 days. The last Group [VIII] administered both vitamin C and CDDP for 5 days. Serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities [markers of hepatotoxicity], antioxidants [superoxide dismutase [SOD], glutathione peroxidase [GSHPx], catalase [CAT], glutathione reductase [GSHR] activities and gene expression, glutathione [GSH] content] and lipid peroxidation products [malondialdehyde, MDA] in rat liver tissue were measured. CDDP hepatotoxicity was manifested by an increase in serum ALT and AST, elevation of MDA as well as a decrease in GSH and the activities and gene expression of antioxidant enzymes [SOD, GSHPx, CAT, GSHR] in liver tissues. Serum ALT, AST and hepatic MDA decreased in the combination groups in comparison with the CDDP group. The activities and gene expression of SOD, GSHPx, CAT and GSHR and the GSH concentration increased in the combination groups as compared to the CDDP group. Reduced glutathione and vitamin C either taken before or concomitant with cisplatin attenuated the CDDP hepatotoxicity

Metabolic effects of streptozotocin-induced diabetes in ovarectomized rats

Little information is available about how the changes that occur around the time of menopause might affect management of diabetes mellitus .The present study investigates the metabolic consequences of estrogen deficiency with streptozotocin induced-diabetes. The study was performed on 130 female Wistar rats, allocated into 4 groups: control [Sham]; diabetic [STZ]; ovarectomized [OVX] and ovarectomized diabetic [OVX-STZ] .Rats were subjected to determination of body weight and body mass index [BMI]. Estimation of blood glucose, plasma levels of insulin, estradiol, leptin, malondialdehyde, lipids, atherogenic index as well as in vitro diaphragmatic glucose uptake and renal glucose output. OVX- STZ rats showed significantly lower body weight and BMI than OVX rats. Blood glucose level was significantly higher than Sham, STZ and OVX groups. Diaphragmatic glucose uptake significantly decreased, while renal glucose output significantly increased compared to OVX and Sham groups .Plasma lipid profile in OVX-STZ rats was worse than Sham, STZ and OVX groups as indicated by the significant increase in plasma triglycerides, total plasma cholesterol and LDL-c. Atherogenic index was significantly higher than Sham and OVX rats. Similarly, lipid peroxidation was significantly higher than Sham, STZ and OVX groups. Plasma insulin decreased significantly compared to Sham, STZ and OVX groups, while the decrease in plasma leptin was significant when compared to Sham group. The present study demonstrates that metabolic derangements of combined insulin and estrogen deficiency overweigh the derangement of either hormone deficiency in postmenopausal period

Measurement of oxidized low-density lipoprotein and superoxide dismutase activity in patients with hypertension

Arterial hypertension is an important risk factor for coronary artery disease and cardiovascular-induced morbidity and mortality. It can cause end-organ damages such as cerebrovascular diseases, renal failure, and congestive heart failure. On the other hand, because of elevated blood pressure and rapid blood flow, there is an increase in oxidation and peroxidation reactions. The aim of this study was to evaluate the level of oxidized low-density lipoprotein and superoxide dismutase activity in sera of hypertensive patients. In this case-control study, 70 hypertensive patients without any other important diseases such as congestive heart failure, cardiomyopathy, liver disease, diabetes mellitus, renal disease, or thyroid disease were compared with 70 age-and gender-matched controls. The participants' age range was from 30 to 75 years. Measurement of oxidized low-density lipoprotein in serum was performed by enzyme-linked immunosorbent assay. The activity of superoxide dismutase in serum was measured by enzymatic colorimetry method. The patients' mean age +/- SD was 52.2 +/- 14 years. The controls' mean age +/- SD was 45 +/- 13 years. The level of superoxide dismutase activity in the patients' group was 100_27 U/mL, and in the controls_ group was 105 +/- 11 U/mL. The level of oxidized low-density lipoprotein in the patients' group was 14 +/- 4 mu/L, and in controls it was 7.7 +/- 3 mu/L. Data of this study demonstrated an elevation of oxidized low -density lipoprotein in hypertensive group that may be the result of oxidation processes. Superoxide dismutase activity was decreased in hypertensive patients, which can be the result of elevated oxidation reactions

Decreased Helicobacter pylori-associated gastric epithelial proliferation by concurrent Schistosomal infection

Helicobacter pylori [H. pylori] injection is associated with increased gastric epithelial proliferation, the enhanced epithelial proliferation is important in developing gastric carcinoma. Some developing countries with a high prevalence of H. pylori infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by T-helper cell, type 1 [Th1] response may be modulated by concurrent parasitic infection. Pathogenic helminths of the genus Schistosoma cause T-helper cell, type 2 [Th2] response to parasite eggs. The Th2 response is usually associated with down regulation of Th1 cytokine synthesis. The aim of the present study was to assess whether concurrent Schistosoma mansoni infection with H. pylori has an effect on gastric mucosal injury in view of cell proliferation, apoptosis, pathological changes, nitric oxide and oxyradicals status. Between April 2001 and March 2002, 73 patients [13 child and 60 adults] were subjected to upper gastrointestinal endoscopy for dyspepsia and liver cirrhosis in the National Liver Institute, Menoufiya University. Four biopsy specimens were taken, two from the greater curvature of the antrum and two from the upper body of the stomach, biopsies were obtained from any lesion as well as from apparently healthy mucosa. One snap from each site was preserved in RNA later solution, then kept at -80°C till utilized for estimation of DNA-flow cytometric assay, reduced glutathion [GSH], catalase [CAT], superoxide dismutase [SOD], Nitric oxide [NO], and lipid peroxidation product- malondialdehyde [MDA]-. Diagnosis of bilharziasis was done by stool analysis, or by sigmoidoscopy and rectal snip. OF the 73 patients, 60 patients were cirrhotic [20 Child A, 34 B, 6 C], 48 were H. pylori-positive and 25 H. pylori negative. The mean age in H. pylori positive patients [46.31 +/- 10.7 years] was significantly less than in H. pylori - negative patients [52.8 +/- 7.2 years]. Infection with H. pylori alone correlated with increased DNA s-phase, proliferation activity and apoptosis [sub-G phase] [p 0.04, 0.03 and 0.04] respectively. Concurrent infection with schistosomiasis occurred in 34 patients and it significantly suppressed DNA 5-phase [P=0.001], proliferation activity [p<0.004], and apoptosis [sub-G phase], [p>0.05]. On contrast, concurrent infection had an adverse effect on liver cirrhosis with increased incidence of upper gastrointestinal bleeding. Schistosomal concurrent infection with H. pylori is associated with higher incidence of superficial gastritis, and may complicate liver cirrhosis with increased upper gastrointestinal bleeding. On the other hand, concurrent schistosomal infection may have a protective effect against the possible progression of H. pylori induced gastritis towards gastric carcinoma, by modulating the cytokine profile of the gastric mucosa with suppression of the proliferation activity. A detailed study of the cytokine expression in similar cases is recommended for unraveling the mystery of this phenomenon

Imbalance between free radical propagation and some antioxidants in patients with cataract

The relation of oxidative stress to the occurrence of cataract remains to be undetermined and must be clarified. So, the aim of this work was to study the effect of O2-free radical and some antioxidants in the pathogenesis of senile and diabetic cataract. This work was carried on 30 patients and 10 healthy subjects as control. They were 23 males and 17 females. Their ages ranged from 50 to 64 years. Patients were classified into senile cataract, diabetic without cataract and diabetic cataract groups. Each group included 10 patients. The results of this work showed that, in patients with senile cataract, were non-significant increase of fasting serum glucose [FSG] and serum total bilirubin [serum T. bilirubin] compared with the control group. Serum lipid peroxide [S. LP] and serum ceruloplasmin [S. Cp] were. significantly increased [P<0.05] while plasma superoxide dismutase [SOD] and serum uric acid were significantly decreased [P<0.05] compared with the control group. Moreover, diabetic patients with and without cataract showed a significant increase of FSG, S. total bilirubin. S. LP, S. Cp, and S. uric acid [P<0.05] while plasma SOD was significantly decreased [P<0.05] compared with the control group. Comparative study of the diabetic cataract versus senile cataract and diabetic without cataract, our results showed a significant increase of FSG, S. LP, S. total bilirubin and S. Cp, while there was significant decrease of plasma SOD in diabetic cataract compared with both senile cataract and diabetic without cataract [P1<0.05 and P2<0.05], respectively. S. uric acid was significantly increased in diabetic cataract compared with senile cataract group [P1<0.05] while it was non-significantly increased compared with diabetic without cataract group. Also, aqueous humor study of diabetic cataract group versus senile cataract group showed that LP and uric acid were significantly increased [P<0.05] while SOD was significantly decreased [P<0.05]. Correlation study revealed that, age was significantly and positively correlated with LP, but negatively correlated with SOD both in serum and aqueous in all patient groups. FSG was significantly and directly correlated with serum and aqueous LP, uric acid, S. total bilirubin, and S. Cp in diabetics with and without cataract. Moreover, serum and aqueous LP was significantly and inversely correlated with serum and aqueous SOD in all patient groups, while, it was positively correlated with S. total bilirubin, and S. Cp in diabetics with and without cataract. We could conclude that the imbalance between generation of O2-free radical and plasma SOD may have an etiological implication in the occurrence of cataract

Protective role of dispercam against adverse effects of cefotaxime on lipid peroxidation and the activities of lipoxygenase and some antioxidant enzymes

Malondialdehyde [MDA] level and the activities of superoxide dismutase [SOD], catalase and lipoxygenase were determined in liver of guinea pigs treated with: 1-Cefotaxime, 2-[Cefotaxime plus dispercam], 3- dispercam, and compared their results with the control data. Cefotaxime increased both the level of MDA and the activities of SOD, catalase and lipoxygenase enzymes as compared with the normal control data. However, the treatment of guinea pigs with cefataxime plus dispercam decreased both level of MDA and the activities of SOD, catalase and lipoxygenase enzymes as compared with the data of cefotaxime treatment, i.e., Dispercam treatment decreased the side effects of cefotaxime treatment. The results also showed that, the treatment with dispercam only decrease the activities of SOD, catalase and lipoxygenase and also the level of MDA as compared with the normal control data

Some biochemical aspects associated with accelerated atherosclerosis in chronic renal failure

This study included fifteen patients diagnosed as chronic non-nephrotic renal failure to whom dialysis had never been done and thirty patients diagnosed as chronic non-nephrotic renal failure who were under maintenance hemodialysis for at least one year. In addition a control group of 10 healthy subjects of matched age, sex and socioeconomic status was included in the study. To all subjects the following was done: serum Lp[a], apolipoprotein-B, Thiobarbituric acid reactive substances [TBARS] and lipid profile. Serum Lp[a] was found to be higher in both chronic renal failure groups, either dialyzed or un-dialyzed, when compared to controls. TBARS levels were significantly elevated in both dialyzed and undialyzed group of patients than the control group. The prevalence of cardiovascular diseases was 20% in the non-dialyzed group of patients and 40% in the dialyzed group in-spite of the normal or subnormal serum total cholesterol. This point out to the possibility that other lipoprotein abnormalities such as the increased Lp[a] and increased lipid peroxidation are probably incriminated in the prevalence of accelerated atherosclerosis. It could be concluded that Lp[a] is an independent risk factor for atherosclerosis in chronic renal failure patients. This risk increases with the process of hemodialysis. Increased lipid peroxidation in these patients is an additional factor for the accelerated atherosclerosis