Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress.

Various beneficial properties has been attributed to Nigella sativa, including its antioxidant potential. Previously, it was reported that supercritical fluid extraction (SFE) could be used to obtain N. sativa extract rich in antioxidants. In the present study, N. sativa extracts prepared using the previously optimized SFE as well as the traditional Soxhlet extraction approaches were analyzed for various known antioxidants. N. sativa extracts were found to prevent protein carbonyl formation as well as depletion of intracellular glutathione (GSH) in fibroblasts exposed to toluene. Furthermore, partially purified SFE and Soxhlet fractions could prevent loss of hepatic GSH in toluene-induced oxidative stressed Wistar rats as well as in L929 fibroblasts. The results showed that SFE-produced N. sativa extract is richer in antioxidants than the Soxhlet approach. It was also shown using preparative silica gel and reverse phase chromatography that different fractions of SFE-extracted or Soxhlet-extracted N. sativa had different levels of protective effects with regards to GSH depletion in vivo as well as in cell culture. Although fractions rich in thymoquinone were found to be most potent in terms of antioxidant capacity, the data indicates that the protective effects of N. sativa may not only be due to thymoquinone, but perhaps other antioxidants.

Effects of streptozotocin-induced long-term diabetes on parietal cell function and morphology in rats.

Gastric pathology is a common complication in diabetes mellitus. The aim of the study was to evaluate the functions and morphological changes of the parietal cells of the rat stomach after streptozotocin-induced diabetes. Diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). The rats were weighed weekly and sacrificed after 6 months. The glandular portion of the stomach was removed and processed for H(+)-K(+)-ATPase immunohistochemistry and light and electron microscopy studies. Acid secretion was measured in vivo. After 6 months of diabetes, the mean weight of the rats was significantly lower (P < 0.001) compared to control. The mean weight of the stomach to body weight percentage increased significantly (P < 0.001) compared to control. The blood glucose level in diabetic rats was significantly higher (P < 0.001) than in normal control. Diabetic rats showed significant (P < 0.001) decrease in basal and stimulated acid secretion when compared to control. Electron micrographs of the parietal cells of glandular stomach of diabetic rats revealed significant (P < 0.0002) reduction in the number of mitochondria and a small though not significant increase in the number of canaliculi in the parietal cells compared with normal. Immunohistochemistry showed reduced H(+)-K(+)-ATPase (P < 0.00001) compared to control. Long-term diabetes induces morphological as well as functional changes in gastric parietal cells. The decrease in the number of mitochondria accompanied by reduced in H(+)-K(+)-ATPase in parietal cells may explain the reduced acid secretion observed in diabetics.

The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits.

Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion, acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro preparations. The effect of omeprazole was also investigated for comparison. Dimaprit-induced acid secretion was significantly (P < 0.05) inhibited by both PPIs in a dose-dependent manner. In the isolated rabbit gastric glands, both PPIs elicited marked reductions in histamine- and dbcAMP-evoked acid secretion with similar potency. The lesions induced by either AE or INDO were significantly (P < 0.05) reduced in the presence of either esomeprazole or omeprazole compared to control values. Increasing doses of esomeprazole before AE treatment resulted in a marked degree of cytoprotection and an elevation in the concentration of bound PGE2 in the stomach tissue homogenate. The results show that esomeprazole and omeprazole were equally effective against gastric haemorrhagic lesions induced by either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro. The gastro-protective effect of esomeprazole was found to be proportional to the bound PGE2 levels in the glandular area of the stomach.

Alterations in atrial natriuretic peptide and its receptor levels in long-term, streptozotocin-induced, diabetes in rats.

Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro- and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long-term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)-induced 8-month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ-induced, 8-month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ-induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma (P < 0.05), kidney (P < 0.01), heart atria (P < 0.05), and ventricles (P < 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex (P < 0.05), juxtaglomerular medulla (P < 0.05), and papilla (P < 0.05) of 8-month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ-induced diabetic heart merits additional study.

Temporal and region-dependent changes in muscarinic M4 receptors in the hippocampus and entorhinal cortex of adrenalectomized rats.

Long-term adrenalectomy induces a dramatic loss of cells in the dentate gyrus and CA1-CA4 fields of the hippocampus resulting in an impairment of cognitive functions such as spatial learning, memory and exploratory behaviour. Muscarinic M1 and M4 receptor levels in the hippocampus and entorhinal cortex of adult male Wistar rats were examined 3, 14, 30, 90, and 150 days after adrenalectomy. Receptor levels in the entorhinal cortex and the hippocampus were determined by quantitative autoradiography using 125I-M1-toxin-1 and 125I-M4-toxin-1, M1 and M4 subtype selective antagonists, respectively. Moreover, the level of hippocampal M1 and M4 muscarinic receptors were evaluated 1 month after adrenalectomy by immunoblot analysis. Adrenalectomy induced apoptotic processes were examined by analysing apoptotic markers using Western blot analysis. No significant changes were observed in the level of muscarinic M1 receptors in the entorhinal cortex, the dentate gyrus and in the different CA fields of the hippocampus of adrenalectomized (ADX) rats. However, M4 receptors showed a significant decrease in the entorhinal cortex (at 3 days), dentate gyrus and CA4 (at 14 days), CA3 (at 30 days), and CA2 and CA1 (at 90 days) after adrenalectomy. Moreover, a decrease in the level of M4 receptors was detected in ADX rats 1 month after adrenalectomy as compared with sham groups using M4 specific antibody. Apoptotic markers such as PARP and p53 were significantly increased whereas Bcl-2 marker was decreased in ADX rat brain homogenates compared to controls. Our results show that M1 and M4 receptors are differentially affected by adrenalectomy and indicate that these subtypes have different functions in the hippocampus. Our data on time and region-dependent decreases in hippocampal M4 receptors indicate that the M4 receptor subtype is influenced by adrenal hormones and suggest that the M4 receptor might be linked to memory function in the hippocampus.

Mechanisms of action of leptin in preventing gastric ulcer.

AIM: To investigate the effects of leptin (1-20 microg/kg) on acidified ethanol (AE)- and indomethacin (Indo)-induced gastric lesions in rats and compare it with ranitidine, lanso-prazole, and omeprazole and to determine its mechanisms of actions. METHODS: Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors (PPIs) lansoprazole and omeprazole, or H(2)-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE(2) concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content. RESULTS: Subcutaneous administration of leptin, two PPIs lansoprazole and omeprazole or H(2)-receptor antagonist ranitidine 30 min before AE or Indo produced a dose-dependent and reproducible inhibition of gastric ulcers (GUs). This inhibition was found to be more potent than other antagonists used. In N(G)-nitro L-arginine methyl ester (L-NAME)-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced, compared to rats without L-NAME pretreatment. However, the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE(2) level in the gastric glandular tissues. Leptin also increased mucus secretion. CONCLUSION: The results of the present study show that leptin inhibits GU formation by AE or Indo in a dose-dependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.

Alterations in atrial natriuretic peptide and its receptors in streptozotocin-induced diabetic rat kidneys.

In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose levels were used as indices of diabetes mellitus in the STZ-induced rats. There was a significant loss in the body weight of the diabetic rats compared to controls. The efficacy of STZ administration was confirmed by rising blood glucose levels, which were significantly higher in diabetic rats compared to controls. Plasma ANP concentration was significantly greater in the diabetic rats in comparison with controls. Moreover, our immunohistochemical results show that the expression of ANP in diabetic rats was higher than that in age-matched controls. ANP was observed in the cells lining the proximal convoluted tubules in the cortex. The distribution and levels of ANP receptors in the kidneys of diabetic rats and age-matched controls were investigated using quantitative receptor autoradiography. Our results demonstrate significant decrease in ANP receptors in the kidneys of the diabetic rats compared to controls. The significant decrease was found in the juxtaglomerular medulla, inner medulla, and the papillae. The decrease in ANP receptors observed in the diabetic kidneys could have pathological consequences resulting in renal resistance to ANP in diabetes.