1-Maha M. Deif and Howaida A. Nounou. The possible role of calcitonin gene-related peptide in estradiol cardioprotection in cases of isoproterenol-induced myocardial ischemia in rats. Bulletin of Alexandria faculty of medicine.2008; 44 (2) : 475-481
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.
Material and methods: 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.
Results: 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.
Conclusions : 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.
List of Abbreviations:
Calcitonin gene-related peptide (CGRP)
Creatine kinase (CK)
Lactate dehydrogenase (LDH)
2-Ghoneim M, Howaida A. Nounou. , Deif M& Baraka A. The possible renoprotective effect of some drugs inducing heat shock proteins in renal ischemic reperfusion injury in rats. Bulletin of Alexandria faculty of medicine.2008; 44 (2) :495-504.
Objectives: 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.
Methods: 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.
Results: 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 &IVb) compared to those that didn't receive quercetin(IIIa &IVa).
Conclusions: 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 & 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.
List of Abbreviations: Renal ischemia reperfusion injury(RIRI),Acetylsalicylic acid (ASA) ,Cyclooxygenase (COX) ,Myeloperoxidase (MPO) ,Nonsteroidal anti-inflammatory drugs(NSAID).