Protective effects of either C-peptide or l-arginine on pancreatic ß-cell function, proliferation, and oxidative stress in streptozotocin-induced diabetic rats.

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l-arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1-control nondiabetic, 2-diabetic (no treatment), 3-diabetic + C-peptide, and 4-diabetic + l-arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l-arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l-arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.

Somatostatin analogue, Octreotide, improves restraint stress-induced liver injury by ameliorating oxidative stress, inflammatory response, and activation of hepatic stellate cells.

The aim of this study is to investigate the effect of somatostatin (SST) analogue, Octreotide, on some features of liver injury induced by immobilization stress (IS) in adult male albino rats. Eighteen adult male albino rats were randomly divided into three equal groups: control, IS, and Octreotide-treated stressed groups. Octreotide (40 µg/kg body weight, subcutaneously) was administrated twice daily for 8 days during the exposure to IS. Octreotide was found to reduce the IS significantly and induce elevations in the plasma level of corticosterone, liver transaminases, and tumor necrosis factor α (TNF-α) as compared with IS group. Furthermore, Octreotide administration has significantly elevated the decline in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels observed with IS in the hepatic tissue. Additionally, Octreotide treatment provided protection against the histopathological changes in the stressed liver in the form of significant reduction in the mean number of degenerated hepatocytes, the area % of collagen fibers, and glial fibrillary acid protein (GFAP) immunostaining with a significant increase in the mean number of normal hepatocytes. In conclusion, stressed rats showed disturbed liver functions and its oxidant-antioxidant status with highly expression hepatic stellate cells (HSCs), which were all improved by Octreotide administration, SST analogue.

Prevention of renal ischemia/perfusion-induced renal and hepatic injury in adult male Albino rats by oxytocin: role of nitric oxide.

BACKGROUND: Oxytocin (OT) has an anti-inflammatory and antioxidant effect in the different inflammatory models. The current study aimed to evaluate the protective function of OT in renal and hepatic damages triggered by renal ischemia/reperfusion (IR) in rats. Moreover, the effect of NG-nitro-l-arginine methyl ester (l-NAME) was investigated on the kidney and liver functions in renal IR model. METHODS: Twenty-four rats were divided into four groups (six rats each) as follows: (1) Sham-operated group; (2) Renal IR group; (3) Renal IR+OT group; (4) Renal IR+OT+l-NAME. OT (1 mg/kg, i.p.) was administered 30 min prior to the induced ischemia and was repeated immediately before the reperfusion period. l-NAME (10 mg/kg, i.p.) was given 45 min before IR injury. RESULTS: The results revealed that OT significantly attenuated the IR-induced elevations in the serum urea, creatinine, liver transaminases, and TNF-α levels, while nitric oxide (NO) and Bcl-2 levels were significantly increased compared with the IR group. OT also significantly compensated the decrease in the total antioxidant capacities (TAC) and lowered the elevated malondialdehyde (MDA) levels that were observed with renal IR in the renal and hepatic tissues. CONCLUSIONS: In conclusion, OT ameliorates renal and hepatic damages triggered by renal IR, and this defense involves the suppression of inflammation and apoptosis with regulation of oxidant-antioxidant status. In addition, administration of l-NAME prior to OT partially reversed the protective effect of OT ensuring that one of the protective effects of OT was through the NO production.

Linking senile dementia to type 2 diabetes: role of oxidative stress markers, C-reactive protein and tumor necrosis factor-α.

Diabetes is considered an independent risk factor for cognitive impairments. OBJECTIVES: The aim of this study was to evaluate the cognitive disorder of elderly outpatients with and without type 2 diabetes (T2DM) in releationto oxidative stress markers and some inflammatory markers Methodology: Two hundred and twelve participants were classified into four groups according to their fasting blood glucose level, glycosylated hemoglobin (HbA1c) and mini-mental state examination (MMSE) score. Control subjects were 118 subjects, diabetic group without dementia was 54 subjects, diabetic group with dementia was 26 subjects and 14 subjects of dementia without diabetes. Body mass index and waist/hip ratio were measured. Blood glucose, HbA1c, plasma malondialdehyde (MDA), total antioxidant activity (TAC), and some inflammatory markers: C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were measured. RESULTS: Diabetic patients have significant increases in FBG, HbA1c, MDA with a significant decrease in TAC compared to control group. In all groups of patients, the levels of CRP, and TNF-α were significantly higher as compared to control group. The highest level of inflammatory markers was detected in diabetic group with dementia. MMSE score was negatively correlated with HbA1c levels and TNF-α and HbA1c levels were positively correlated with all inflammatory markers. In multivariate logistic regression analysis, MDA,CRP, Hb1c, TNF-a, and FBG were the most predictive risk factors for dementia Conclusions: These results suggest that a decrease in anti-oxidant levels and an increase in anti-inflammatory and oxidative stress markers might be involved in the pathophysiology of cognitive disorder associated with T2DM.

Effect of exposure and withdrawal of 900-MHz-electromagnetic waves on brain, kidney and liver oxidative stress and some biochemical parameters in male rats.

Increasing use of mobile phones in daily life with increasing adverse effects of electromagnetic radiation (EMR), emitted from mobile on some physiological processes, cause many concerns about their effects on human health. Therefore, this work was designed to study the effects of exposure to mobile phone emits 900-MHz EMR on the brain, liver and kidney of male albino rats. Thirty male adult rats were randomly divided into four groups (10 each) as follows: control group (rats without exposure to EMR), exposure group (exposed to 900-MHz EMR for 1 h/d for 60 d) and withdrawal group (exposed to 900-MHz electromagnetic wave for 1 h/d for 60 d then left for 30 d without exposure). EMR emitted from mobile phone led to a significant increase in malondialdehyde (MDA) levels and significant decrease total antioxidant capacity (TAC) levels in brain, liver and kidneys tissues. The sera activity of alanine transaminase (ALT), aspartate aminotransferase (AST), urea, creatinine and corticosterone were significantly increased (p < 0.05), while serum catecholamines were insignificantly higher in the exposed rats. These alterations were corrected by withdrawal. In conclusion, electromagnetic field emitting from mobile phone might produce impairments in some biochemicals changes and oxidative stress in brain, liver and renal tissue of albino rats. These alterations were corrected by withdrawal.

Effect of acute immobilization stress with or without a heme oxygenase inducer on testicular structure and function in male albino rats.

BACKGROUND: Stress disturbs homeostasis and may induce various disorders. Immobilization stress (IS) induced due to reduced area provided for mobility results in the imbalance of oxidant and antioxidant status. Stress leads to male reproductive dysfunction in many species, including rodents and humans. Induction of heme oxygenase-1 (HO-1), the rate limiting enzyme in heme degradation, increases host antioxidant defenses. We elucidated the protective role of induction of HO-1 by hemin on testicular damage induced by acute IS. METHODS: Male albino rats were immobilized for a period of 6 h. Hemin was given for 3 consecutive days (40 µmol/kg/day, s.c.), before subjecting the animals to acute IS. RESULTS: Upregulation of HO-1 following hemin administration was evidenced in our study by increasing carboxyhemoglobin (COHb) level. Histopathological evaluation confirmed that acute IS caused significant testicular tissue injury, which improves in groups pretreated with hemin. Acute IS also caused significant increases in serum catecholamines and corticosterone levels; however, it produced a significant decrease in testosterone level with non-significant changes in luteinizing hormone (LH) level. In addition, it was found that IS significantly increased testicular malondialdehyde (MDA) and decreased catalase activities. The HO-1 inducer (i.e., hemin) significantly decreased catecholamines and corticosterone levels, and increased testosterone and LH levels. Hemin also decreased testicular MDA and increased catalase activities significantly. CONCLUSIONS: Induction of HO-1 protects the testes through its antioxidant and anti-inflammatory effects. Thus, it represents a potential therapeutic option to protect testicular tissue from detrimental effects of IS.

The effects of exercise on C-reactive protein, insulin, leptin and some cardiometabolic risk factors in Egyptian children with or without metabolic syndrome.

BACKGROUND: The prevalence and magnitude of obesity in the children and the adolescents have increased dramatically in the developing countries over the last 20-30 years. The prevalence of metabolic syndrome (MS) in children is increasing. AIM: This study aimed to investigate the changes of C-reactive protein (CRP), leptin, insulin, and blood lipids before and after the exercise therapy in normal and obese children (with or without metabolic syndrome). METHODS: The study covered 49 normal children (control), 32 obese children without metabolic syndrome and 12 obese children with metabolic syndrome. We examined the influence of exercise (3 times/week) for 12 weeks on the levels of serum CRP, leptin, insulin, homeostatic model assessment insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in all groups. RESULTS: There were significant correlations between HOMA-IR and the individual components of the metabolic syndrome. After 12 weeks of exercise, both of the obese children groups, with and without metabolic syndrome, showed reduced body weight, body mass index (BMI), and CRP level, and increased HDL-C level. The percentage of metabolic syndrome decreased from 12.9% before the exercise training to 7.5% after training. Also, there was a significant reduction in BMI (from 47.3 to 32.6%), in systolic blood pressure (from 18.3 to 15.1%) and in HDL-C level (from 18.3 to 9.7%). CONCLUSION: Overweight children have multiple risk factors associated with the metabolic syndrome. 12-week exercise may have a positive effect on reducing risk factors for the metabolic syndrome.