The antiapoptotic effects of sulphurous mineral water and sodium hydrosulphide on diabetic rat testes.

BACKGROUND/AIMS: It is well known that diabetes mellitus is associated with the impairment of testicular function. In the present study, we aimed to study the effects of sulphurous mineral water or sodium hydrosulphide (NaHS) on apoptotic testicular damage in rats with streptozotocin (STZ)-induced diabetes. METHODS: Sulphurous mineral water (as drinking water) or NaHS (14 µmol/kg body weight/day, I.P.) was administered for 7 wks to rats with STZ-induced diabetes. RESULTS: Hyperglycaemia, an overproduction of glycated haemoglobin (HbA1C) and a decline in serum insulin, C-peptide and insulin-like growth factor-I (IGF-I) were observed in diabetic rats. A decline in the serum testosterone level and an impairment of spermatogenesis, as indicated by a histopathological examination of diabetic rats, demonstrated significant testicular damage. Sulphurous mineral water and NaHS treatment may have improved the level of testicular GSH by blocking the overexpression of some apoptosis-related regulatory proteins such as Bax/Bcl-2, cytochrome c, caspase-9 and -3, and p53. This anti-apoptotic potential was associated with an increase in serum testosterone level and the amelioration of hyperglycaemia-related biochemical parameters. The histopathological examination was in harmony with the biochemical and molecular findings. CONCLUSION: Our study provides the first indication that sulphurous mineral water and NaHS may have a novel anti-apoptotic potential that could be a useful treatment in preventing diabetes-induced testicular dysfunction.

Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats.

This study examined the downstream signaling whereby hyperglycemia may lead to myocardial fibrosis and apoptosis in the left ventricle of diabetic rats. The effects of sulfurous mineral water or sodium hydrosulfide (NaHS) as possible modulators were also examined. Sulfurous mineral water (as drinking water) and NaHS (14µmol/kg/day, IP) were administered for 7 week to rats with streptozotocin (STZ)-induced diabetes. Hyperglycemia, overproduction of glycated hemoglobin (HbA1C) and serum decline in insulin, C-peptide and insulin like growth factor-I (IGF-I) were observed in diabetic rats. Up-regulation of gene expressions of nuclear factor (NF-κB), profibrogenic growth factor such as transforming growth factor-ß1 (TGF-ß1), matrix metalloproteniase-2 (MMP-2), procollagen-1 and Fas ligand (Fas-L) were observed in the left ventricle of diabetic rats. A linear positive correlation between TGF-ß1 and MMP-2 was also detected in diabetic group. An increase in hydroxyproline level and a disturbance in oxidative balance were detected in heart of diabetic rats. Sulfurous mineral water and NaHS treatment possibly, by improving cardiac GSH level, counteracted the enhanced expression of NF-κB, the profibrogenic and apoptotic parameters. Histopathological examination was in accordance with the biochemical and molecular findings of this study. We suggest a novel therapeutic approach of sulfurous mineral water and exogenous supplementation of H(2)S in diabetic cardiomyopathy.

Frequent inadequate supply of micronutrients in fast food induces oxidative stress and inflammation in testicular tissues of weanling rats.

Fast food is high in energy density and low in essential micronutrient density, especially zinc (Zn), of which antioxidant processes are dependent. We have tested the hypothesis that frequent fast food consumption could induce oxidative damage associated with inflammation in weanling male rats in relevance to Zn deprivation, which could adversely affect testis function. Zn and iron (in plasma and testicular tissue), plasma antioxidant vitamins (A, E, and C), as well as testicular superoxide dismutase (SOD) and reduced glutathione (GSH), lipid peroxidation indexes (thiobarbituric acid reactive substances (TBARS) and lipoprotein oxidation susceptibility (LOS)), and inflammatory markers (plasma C-reactive protein (CRP) and testicular tumour necrosis factor-alpha (TNF-alpha)) were determined. Serum testosterone and histological examination of the testis were performed also. We found a severe decrease in antioxidant vitamins and Zn, with concomitant iron accumulation. Zinc deficiency correlated positively with SOD, GSH, antioxidant vitamins and testosterone, and negatively with TBARS, LOS, CRP and TNF-alpha, demonstrating a state of oxidative stress and inflammation. We concluded that micronutrient deficiency, especially Zn, enhanced oxidative stress and inflammation in testicular tissue leading to underdevelopment of testis and decreased testosterone levels.

Dietary fatty acid unsaturation levels, lipoprotein oxidation and circulating chemokine in experimentally induced atherosclerotic rats.

The dietary balance of long-chain fatty acids may influence processes involving leukocyte endothelial interactions, such as atherogenesis and inflammation. The relationship between proatherogenic lipoproteins and chemotactic motility is still controversial. However, the interaction of the former can increase recruitment of monocytes to the vessel walls and accelerate the events of atherogenesis. The current study examined the effects of unsaturated fatty acid levels on the oxidative susceptibility of lipoprotein, chemokine expressions and their relationship to atherosclerotic lesion development in experimental rats. Male Wistar rats were fed an atherogenic diet for 4 months and the diet was then supplemented with 10% v/w of virgin olive oil (OO group), sunflower oil (SO group) or fish oil (FO group) for 4 and 8 weeks. Blood samples were collected at four time points: at baseline, after feeding with the atherogenic diet and during the dietary regimen (4 and 8 weeks). Plasma lipid profile and lipoprotein oxidative susceptibility (LOS), C-reactive protein (CRP), monocyte chemoattractant protein (MCP-1), and regulated upon activation normal T-cell expressed and secreted (RANTES) were measured. The superoxide dismutase (SOD) and reduced glutathione (GSH) antioxidant activities were also studied in aortic segments. Histological assessment of the aortic segment was determined. Compared to baseline data, the high-fat and cholesterol-enriched diet increased atheroma formation, plasma LOS and inflammatory indexes (CRP, MCP-1, RANTES). However, it dramatically reduced aortic SOD and GSH contents. Dietary treatment of atherosclerotic rats with OO greatly reduced LOS and remarkably increased aortic SOD and GSH contents as compared to the SO- and FO-treated groups. The FO-supplemented diet had a more pronounced lowering effect on MCP-1 and RANTES compared to the OO and SO diets. In conclusion, this study demonstrated a strong relationship between LOS and circulating levels of chemokines. OO is a potent antioxidant and moderate anti-inflammatory, which effectively reduced aortic atherosclerotic lesions more than the SO- or FO-treated groups in male Wistar rats.

Chronic effects of clozapine administration on insulin resistance in rats: evidence for adverse metabolic effects.

Chronic treatment with the atypical antipsychotics clozapine has been associated with an increased risk for deterioration of glucose homeostasis, leading to hyperglycemia and insulin resistance diabetes. The present study mainly aimed to investigate possible mechanisms underlying clozapine-induced hyperglycemia. Male Wistar albino rats were randomly divided into two groups (each consists of 12 rats). The first group received clozapine orally at a dose of 10mg/kg body weight daily for 6 weeks, while the other group received the drug vehicle only and served as the control group. At the end of the six weeks, hyperglycemia, hyperinsulinemia and insulin resistance, as indicated by Homeostatic model assessment of insulin resistance (HOMA-IR), were observed in the clozapine group as compared with the control group. This disturbance in glucose regulation was associated with non-significant changes in body weight, serum cortisol level, and hepatic glycogen content. The Clozapine group showed a significant increase in hepatic phosphorylase activity and in the gene expression level of hepatic glucose-6-phosphatse (G6Pase) enzymes compared to the control group. It can be concluded that clozapine-induced hyperglycemia and insulin resistance occur in a manner mostly independent of weight gain, and may be attributed to an increase in hepatic phosphorylase activity and increased expression level of G6Pase.

Nicotine and vascular endothelial dysfunction in female ovariectomized rats: role of estrogen replacement therapy.

OBJECTIVES: The protective effects of estrogen replacement therapy (ERT) against oxidative injury and endothelial dysfunction in the aortic tissues induced with nicotine in ovariectomized (OVX) rats were investigated. METHODS: Female rats were divided into a sham-operated group (n = 8) and four groups in which OVX rats received either vehicle (0.1 ml sesame oil, i.m., n = 8), or nicotine (0.1 mg/kg, s.c., n = 8), or estradiol benzoate (0.1 mg/kg, i.m., n = 8), or both nicotine and estradiol benzoate (n = 8) starting at week 5 after the surgery and continuing for the following 6 weeks. KEY FINDINGS: ERT was effective in preventing the rise in plasma lipid profile, atherogenic index and the level of induced endothelin-1 (ET-1) in nicotine-treated OVX rats. It also reduced aortic malondialdehyde, hydroxyproline levels, calcium content and caspase-3 expression induced in nicotine-treated OVX rats. ERT increased serum estradiol, high-density lipoprotein cholesterol and nitric oxide levels in nicotine-treated OVX rats. Furthermore, ERT was effective in restoring reduced glutathione and cyclic guanosine monophosphate contents and endothelial nitric oxide synthase expression in aortic tissues of nicotine-treated OVX rats. CONCLUSIONS: Short-term ERT could be a promising therapeutic strategy to minimize nicotine-induced oxidative stress and vascular endothelial dysfunction in menopausal women subjected to environmental smoke.

Effect of age receptor blocker and/or anti-inflammatory coadministration in relation to glycation, oxidative stress and cytokine production in stz diabetic rats.

Until now the relation between advanced glycation end products (AGEs) and vascular lesion is still controversial. However, the interaction of the former with a receptor triggers the synthesis of cytokines particularly interleukin 1- beta(IL-1 beta) and tumour necrosis factor- alpha(TNFalpha ). Subsequent release of nitric oxide (NO) may in turn induce certain damage to beta cell islets. Several arguments indicated that AGEs and reactive oxygen intermediates (ROIs) could alter the function of the vessel wall. Therefore, this study was undertaken to investigate the effectiveness of aminoguanidine, AG (inhibitor of AGE formation) joined with omega -3-fatty acids, omega 3FAs (anti-inflammatory immunosuppressive drug) in STZ diabetic rats. Diabetes was induced in 48 female albino Wistar rats by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 50 mg kg (-1)). Diabetic animals were treated with AG (50 mg kg(-1) ) and/or omega 3FAs (12 mg kg (-1)) daily and orally for 4 weeks. Groups of age matched diabetic rats ( n= 10) and healthy animals ( n= 10) served as positive and negative controls. At the end of the study, plasma glucose, fructosamine, total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), the susceptibility of LDL to copper-catalysed oxidation, catalase activity, NO, IL-1 beta, TNF alpha were measured. Histopathological assessment of pancreatic slices were also determined. Diabetes remarkably increased plasma glucose, fructosamine and dyslipidaemia (increased TC, LDLC and decreased HDLC). Oxidative markers like oxidative susceptibility of LDL, catalase activity and NO levels were greatly enhanced. Finally, it increased the synthesis and release of cytokine (IL-1beta and TNF alpha). Treatment of diabetic rats with AG and omega 3FAs markedly reduced the above mentioned parameters. Combined form therapy has a better effect regarding oxidative cell markers, specifically NO level. Finally, omega 3FAs coadministration with AG nearly restored the atrophy of islets of Langerhan's and the peripheral lymphocytic infiltration compared to diabetic and AG treated groups. In conclusion, there is a direct correlation between glycation, oxidative stress and cytokine production with increased propensity of microvascular disorder in STZ diabetic rats. omega 3FA administration with AGE receptor blocker may represent a possible avenue of research for therapeutics directed for alleviating the complication associated with diabetes.