possible role of calcitonin gene-related peptide in estradiol cardioprotection in cases of isoproterenol-induced myocardial ischemia in rats

Relative to its metabolic requirements, heart tissue is one of the most poorly perfused in the body, and ischemia resulting from compromised coronary blood flow can have serious detrimental effects. Estrogen has been suggested to modulate vascular physiology and function from a variety of studies in cellular, animal and human models. Genetic deletion of estrogen receptor results in the development of hypertension in middle-aged male and female mice, resulting in endothelial dysfunction and oxidative stress. Calcitonin gene-related peptide [CGRP], a well characterized vasoactive neuropeptide, is a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products. It was discovered in 1982. CGRP is considered to be a neuromediator of particular importance in the cardiovascular system. Regardless of which estrogen receptor mediates cardioprotection, the mechanisms by which estrogen elicits cardioprotection in females are poorly understood. Hence, the present study was conducted in order to investigate the possible role of CGRP in cardioprotection offered by estradiol pretreatment in cases of isoproterenol-induced myocardial ischemia in rats. The present study was conducted on 24 adult female albino rats, weighing 150-200 gms, fed ad libitum, divided into 3 groups: Group [I]: 8 sham-operated rats that served as control. Group [II]: 8 rats that underwent ovarectomy [day 0] and 7 days later, they were pretreated with estradiol subcutaneously [0.25 mg/kg] for 21 day period. Group [III]: 8 rats that also underwent ovarectomy but stayed without estradiol treatment for 28 days. Group II and III rats were, thereafter, intoxicated with isoproterenol subcutaneously [85 mg/kg] for 2 consecutive days to induce myocardial ischemia. Then, all rats were killed. Blood was collected and serum was assayed for blood lipids, creatine kinase and lactate dehydrogenase activities, serum CGRP was also measured. Heart tissues were homogenized and estimation of cardiac CGRP was done. Serum creatine kinase and lactate dehydrogenase activities were significantly increased in group III rats as compared to group I and II. Serum triglycerides and total cholesterol levels also showed a significant increase in group III rats as compared to group I and II. Serum and cardiac CGRP were significantly increased in group II [estradiol-pretreated rats] as compared to group I and III. Significant positive correlation was found between serum and cardiac levels of CGRP, also between both and serum triglycerides. From the previous results, we can conclude that estradiol may exert a protective effect in cases of isoproterenol-induced myocardial ischemia in rats through increasing serum and cardiac levels of CGRP, decreasing serum lactate dehydrogenase and creatine kinase activities and lowering serum triglycerides and total cholesterol levels as compared to estradiol-untreated rats

possible renoprotective effect of some drugs inducing heat shock proteins in renal ischemic reperfusion injury in rats

Renal ischemia reperfusion [RIRI] injury is a clinically important problem. The aim of this study was to assess the possible renoprotective effect of inducing heat shock proteins by hydrocortisone and acetylsalicylic acid [ASA] in RIRI in rats. The present study was conducted on 56 male albino rats that were divided into four groups. Group I included normal Sham-operated rats that served as control for group II, Group II was subdivided into Group IIa in which renal ischemia reperfusion injury [RIRI] was induced and group IIb [in which RIRI was induced and received quercetin [HSP70 inhibitor] 24 hours and again 1 hour prior to the induction of RIRI. Groups III and IV consisted of rats with RIRI that received hydrocortisone without [Group IIIa] or with [Group IIIb] quercetin, and that received ASA without [Group IVa] or with [Group IVb] quercetin, respectively, intramuscularly 24 and 12 hours before and after the induction of RIRI. Thirty hours after induction of RIRI, serum urea concentration and creatinine clearance were assessed. Moreover; renal heat shock protein-70 [HSP70] level and renal caspase-3 activity [as an index of apoptosis] were assessed. A significant increase in serum urea concentration and in renal HSP70 level, and caspase-3 activity together with a significant decrease in creatinine clearance, has been observed in non-treated rats [group II] killed 30 hrs after RIRI compared to Sham-operated rats. Administration of hydrocortisone or ASA resulted in a significant decrease in serum urea concentration and in renal caspase-3 activity as well as a significant increase in creatinine clearance and a significant increase in renal HSP70 in rats killed 30 hrs following RIRI [group III and IV] compared to non-treated rats with RIRI. Induction of HSP70 mediated the renoprotective role of both drugs evidenced by a significant decrease in renoprotective effect of either drug in the groups that received quercetin [IIIb and IVb] compared to those that didn't receive quercetin [IIIa and IVa]. This study demonstrates a role for HSP70 in protection against RIRI. Pharmacological strategies to increase stress protein expression have potential merit to prevent ischemic injury to the kidney and other organs. The ability of hydrocortisone and ASA to induce ischemic tolerance suggests that there are advantages in their application in RIRI. First, either is a safe drug in clinical practice. Second, the induction time of ischemic tolerance is relatively rapid after administration of either. Third, there is no additional or special equipment required for the induction of tolerance. Clinical studies will be necessary to evaluate the therapeutic properties of either drug in preventing I/R injury not only in kidneys but also in other solid organs

Role of H2 receptors in the regulation of vascular endothelial growth factor level in experimental peptic ulcer in rats

Peptic ulcer is one of the most common clinical diseases. The incidence rate of peptic ulcer has been on the rise over the last two decades. The repair of gastric ulcer requires the reconstitution of epithelial structures and underlying connective tissue, including vessels and muscle layers. This complicated sequence of events requires a high degree of coordination among different cell types, which is regulated by several factors, the most important and best recognized has been vascular endothelial growth factor [VEGF], also some major proinflammatory cytokines namely tumor necrosis factor alpha [TNF-alpha]and interleukin-l0 [lL-10]. This study was carried out to study the role of H2 receptors on the expression of VEGF and proinflammatory cytokines in experimental peptic ulcer using the H2 receptor stimulant [histamine] and H2 receptor blocker [ranitidine]. This study was conducted on 40 adult male albino rats weighing from 200-250 grams each. Animals were divided into 4 groups each of 10 rats namely: group 1; normal healthy rats used as control, group 2; rats with experimental peptic ulcer without treatment, group 3; rats with experimental peptic ulcer treated with H2 receptor stimulant histamine, and group 4; rats with experimental peptic ulcer treated with H2 receptor antagonist ranitidine. Rats from all groups were sacrificed on the fourth day after the induction of peptic ulcer. Histamine significantly increased serum VEGF levels in group 3 rats as compared to all other studied groups. Histamine also significantly increased serum IL-10 levels while it decreased serum TNF-alpha in experimental peptic ulcer rats. Ranitidine significantly decreased serum VEGF levels in group 4 rats as compared to histamine treated group 3 rats but showed no significant difference in serum VEGF levels as compared to either to normal control or in untreated peptic ulcer rats. However, ranitidine increased the levels of both serums IL-10 and TNF-alpha as compared to group 2, although it reversed the actions of histamine on both cytokines decreasing IL-10 and increasing TNF-alpha serum levels. It can be concluded that histamine may exhibit protective effect against gastric ulcer through increasing VEGF levels and enhancing angiogenesis. This gastroprotection could be related to stimulation of H2 receptors. Ranitidine could provide gastroprotection through other mechanisms such as the powerful and selective inhibition of gastric acid secretion. However, its effect on VEGF production should be considered.Ranitidine, in combination with histamine, should be extensively studied because it may reduce ulcer. area by reducing inflammatory cytokine levels while increasing gastric mucosal blood flow

Effect of melatonin on some bone turnover markers in ovarectomized rats

This study was carried out to evaluate the effect and the mechanism of action of melatonin on some bone markers in ovarectomized bone loss in rats. 32 female albino rats underwent either bilateral laparotomy [sham, n=8] or bilateral ovarectomy [Ovx, n=24]. The Ovx rats were divided into 3 groups, each of 8 rats; Vehicle-treated [Ovx], estrogen-treated [E2] and melatonin-treated [Mlt] group. After 14 weeks treatment, blood and urine were collected. Serum osteoprotegerin [OPG], inhibin, follistatin, and alkaline phosphatase [ALPase] were determined as bone markers. In addition, urinary Deoxypyridinoline [uDPD] was assayed. Serum OPG, inhibin and follistatin levels significantly decreased upon Ovx. They increased upon either treatment with E2 or Mlt with non- significant difference in between as compared to Ovx group. In addition, serum ALPase and uDPD significantly increased on Ovx and decreased with either therapy as compared to Ovx one with non- significant difference between both therapies. The results revealed that administration of Mlt inhibited high bone turnover and prevented calcium loss in ovarectomized rats. This may be through increasing OPG, inhibin and/or follistatin levels. Mlt could be a candidate for the treatment of postmenopausal osteoporosis