Hydrogen sulfide renal protective effects: possible link between hydrogen sulfide and endogenous carbon monoxide in a rat model of renal injury.

Hydrogen sulfide (H2S), along with nitric oxide (NO) and carbon monoxide (CO), proved to have renoprotective effects in various renal diseases. Therefore, this study investigated the renoprotective effect of H2S, in a renal injury model, and its crosstalk with other gasotransmitters such as CO. Thirty-two adult rats were divided into four groups: control, gentamicin (GEN)-treated, GEN + sodium hydrosulfide (NaHS), and GEN + NaHS + zinc protoporphyrin (ZnPP) groups. GEN was used to induce renal injury, NaHS is a water-soluble H2S, and ZnPP is a selective heme oxygenase-1 (HO-1) inhibitor used to inhibit CO synthesis in vivo. NaHS improved kidney functions in the GEN group as evidenced by significantly lower levels of renal injury markers: serum urea, creatinine, uric acid, urinary albumin excretion, and urinary albumin/creatinine. Moreover, NaHS administration to the GEN-treated group significantly lowered renal levels of NO and tumor necrosis factor-α with an increase in total antioxidant, HO-1, and interleukin-10 levels. Furthermore, NaHS administration downregulated the GEN-induced overexpression of the renal inducible nitric oxide synthase (iNOS) and upregulated the suppression of endothelial nitric oxide synthase (eNOS) with improvement in the histological examination and periodic acid Schiff (PAS) staining. However, this improvement in kidney function produced by NaHS was reduced by combination with ZnPP but still improved as compared with the GEN-treated group. The renoprotective effects of H2S can be through its effects on renal tissue antioxidants, pro-inflammatory and anti-inflammatory cytokines, and expression of eNOS and iNOS which can be partially dependent on CO pathway via induction of HO-1 enzyme.

The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy.

This work aims to investigate the renal effect of hydrogen sulfide (H2 S), in the experimentally induced diabetic nephropathy, besides the role of activation of АТP-sensitive potassium (KАTP ) channel in that effect. Thirty-two adult male albino rats randomly divided into four groups: Control, streptozotocin-induced diabetic (diabetic nephropathy [DN]), DN+NaHS (the H2 S inducer), and DN+NaHS+Glibenclamide (a selective KАTP channel blocker) groups. Results showed that kidney functions in the diabetic group improved by NaHS proved by the significant decrease in the measured renal injury markers when compared with the diabetic group with an obvious role of inflammation and oxidative stress. However, the improved kidney functions produced by NaHS was reduced by the combination with Glibenclamide. Glibenclamide combination led also to a significant increase in renal total antioxidant capacity, in addition to a significant decrease in renal total nitric oxide (NO) level. Аccordingly, the results from the present work revealed that the renoprotective effects of H2 S in the case of DN through its effects on renal tissue antioxidants and NO can be partially dependent on activation of KАTP channels, while its effect on renal tissue proinflammatory cytokines is independent of it.

Mechanism of the neuroprotective effect of GLP-1 in a rat model of Parkinson's with pre-existing diabetes.

Several studies have suggested the association between neurodegenerative diseases and diabetes mellitus (DM), DM causes cognitive impairment with age, but its effect is not well known in Parkinson's disease (PD). As a member of the incretin family, Glucagon-like peptide-1 (GLP-1) has glycemic regulation functions. It also exerts many additional effects on different tissues through its receptor's widespread expression. OBJECTIVE: our aim is to investigate the effect of pre-existing diabetes on the severity of PD in male albino rats, and to find out whether GLP-1 could improve PD symptoms in diabetic animals in addition to its hypoglycemic effect, and how it could do that. METHODS: 75 adult male albino rats were equally divided into: Control, Parkinson's, Diabetic Parkinson's, Diabetic Parkinson's + low dose exenatide (GLP-1 receptor agonist), Diabetic Parkinson's + high dose exenatide group. Blood glucose and insulin, striatal dopamine, some striatal oxidative stress and inflammatory markers, and the catalepsy score were measured. RESULTS: Pre-existing of diabetes before initiation of PD raises the severity of PD shown by the more significant increase in catalepsy score, and the more significant decrease in striatal dopamine level. GLP-1 effects extend beyond their hypoglycemic effects only since it has a direct anti-oxidant, and anti-inflammatory neuronal effect with increasing the striatal dopamine and improving the catalepsy score in a dose dependent manner. CONCLUSIONS: Diabetes increases the severity of impairment in PD, and GLP-1 improve it through its direct neuronal effect in addition to its indirect effect through producing hypoglycemia.

Impact of chronic exercise on counteracting chronic stress-induced functional and morphological pancreatic changes in male albino rats.

Chronic stress has been linked to many diseases resulted from dysfunction of both the nervous system and peripheral organ systems. Yet, the effects of chronic stress on the pancreas have received relatively little attention. This work aims to investigate the influence of chronic stress exposure on both the endocrine and exocrine pancreatic function and morphology and its possible mechanism of action, and also to evaluate the impact of chronic exercise with moderate intensity on ameliorating the stress-induced pancreatic changes. Forty adult male albino rats were used and divided into four groups: control group, exercised group (3 weeks of swimming exercise), stressed group (3 weeks of immobilization stress), and stressed group practicing exercise (3 weeks of exercise, concomitant with 21 daily sessions of stress). On the final day of the experiment, all rats were sacrificed. Biochemical, immunohistochemical, and histological studies were conducted. The results showed that chronic immobilization stress produced hyperglycemia, hyperinsulinemia, and increased homeostatic model assessment of insulin resistance index (HOMA-IR) with increasing exocrine pancreatic injury markers by increasing oxidative and inflammatory status of the pancreatic tissue. Histological study showed the injurious effect of stress on the morphology of pancreatic tissue. Physical exercise protected the pancreas from the negative effects of stress through its anti-inflammatory and anti-oxidative effects, evidenced by increasing pancreatic interleukin 10 and total antioxidant capacity and decreasing pancreatic tumor necrosis factor-alpha, and malondialdehyde with ameliorating most of the histological changes induced by stress exposure. Physical exercise effectively counteracts chronic stress-induced pancreatic changes through different mechanisms.

Evidence of the protective effect of l-arginine and vitamin D against monosodium glutamate-induced liver and kidney dysfunction in rats.

Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible MSG-induced injurious effects on some organs have been stated in experimental animal models. Thus, in this study we tried to clarify effect and possible mechanism of action of MSG on liver and kidney, and if this results affected by the addition of l-Arginine or vitamin D to it. Animals divided into; Control, MSG treated, MSG + vitamin D treated, MSG + L-arginine treated group. Serum separated to determine liver and kidney function parameters. Kidneys and livers dissected out for histological examination and for assay of oxidative stress markers. RESULTS: MSG increased body weight and produced liver and kidney dysfunctions. The MSG-induced oxidative liver and kidney damage was proved. Vitamin D and l- Arginine have been shown to protect and restore the liver and the kidney capabilities in MSG models injury via inhibiting oxidative damage, vitamin D or l- Arginine suppresses the increased food intake and body weight gain induced by MSG. CONCLUSIONS: due to injurious effect of MSG, it should be avoided especially in liver or kidney disorders, foods containing excess MSG can be fortified with vitamin D or l- Arginine to overcome its adverse effects.

Novel neuroprotective role of hydrogen sulfide in a rat model of stress brain injury.

Hydrogen sulfide (H2S) is a gaseous mediator recognized as important neuromodulator agent in the central nervous system. Since stress is among the most important factors involved in several pathophysiological brain processes. This study aim to investigate the effect of exogenous H2S on the possible negative effect of stress on the brain of rats and the underlying mechanisms. Rats were divided into 3 groups: control, stressed, H2S treated + stress. Brain injury markers measured were serum S100 protein and gamma enolase. Stress leads to obvious detrimental effects on the brain tissues; it produced significant increase in serum level of the above mentioned brain injury markers, and significant increase in brain levels of nitric oxide (NO), tumor necrosis factor-alpha (TNFα), and malondialdehyde (MDA) the lipid peroxidation degradative product along with significant decrease in brain glutathione level. H2S pre-treatment before stress application abolished the above detrimental effects of stress on the brain tissue since it produced significant decreases in the stressinduced expression of brain injury markers, brain TNFα, brain NO and brain MDA, and significant increases in the stress-induced reduction of brain glutathione. H2S has significant neuroprotective role in the nervous system against stress-induced significant brain injury through its antioxidant and anti-inflammatory effects.

Protective effect of C-peptide on experimentally induced diabetic nephropathy and the possible link between C-peptide and nitric oxide.

Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by NG-nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.

Gender differences in ghrelin response to chronic immobilization stress in rats: possible role of estrogen.

Ghrelin is a peptidergic hormone known to be one of the main hormones involved in the regulation of energy balance. Here we evaluated ghrelin response to stress in rats after ovariectomy and during estradiol benzoate (EB) therapy and compared results of males and females, to know whether ghrelin is involved in disordered eating behaviors in response to stress, and for understanding differences between males and females in food intake and weight gain especially during stress. 96 adult rats were classified into; male, female, ovariectomized (Ovx), Ovx with EB. Half animals of each group were exposed to immobilization stress 20 min/day for 21 days. We found that chronic stress significantly augments serum ghrelin levels in both males and females, which is correlated with an increase in food intake and body weight. Females displayed significant higher ghrelin than males especially in response to stress, ovariectomy suppresses serum ghrelin in both unstressed and stressed females which is rescued by replacement with EB. EB replacement augments ghrelin response to stress in Ovx female, and reduces food intake and body weight. In conclusion, there is a clear sex difference in ghrelin secretion in response to stress caused by EB, since it amplifies ghrelin response to stress in females.

Gender difference in the development of cardiac lesions following acute ischemic-reperfusion renal injury in albino rats.

Renal ischemia-reperfusion (I/R) is the major cause of acute renal failure. Renal I/R have distant effects on other organs, especially the heart. The purpose of this study was to investigate cardiac lesion following bilateral renal ischemia (50 minutes) and reperfusion (48 hours) in adult rats, to test sex differences in the development of cardiac lesions after acute renal I/R and to investigate the effect of estrogen on this type of cardiac lesions. 70 adult albino rats were divided into 7 groups: control male, I/R male, control female, I/R female, female with bilateral ovariectomy, I/R female with bilateral ovariectomy and I/R female with bilateral ovariectomy treated with estrogen. Renal and cardiac functions in both sexes were deteriorated following acute renal I/R injury proved by the increase in serum urea, creatinine, lactate dehydrogenase and creatine kinase levels. These cardiac lesions are mainly due to the oxidative stress response in the form of the increase in cardiac tissue lipid peroxide, and the decrease in cardiac tissue glutathione reductase, superoxide dismutase and catalase levels. In conclusion, female rats are more protected from the renal and cardiac lesions following acute renal I/R injury than male, since estrogen significantly decreases these lesions mainly by inhibiting the oxidative stress response.