الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
The heme oxygenases (HO), which consist of constitutive and inducible isozymes, catalyze the rate-limiting step in the metabolic conversion of heme to the bile pigments, iron and carbon monoxide (CO). Endogenously produced CO has been shown to possess signaling properties affecting numerous critical cellular functions.
CO is not always an injurious byproduct of heme catabolism but it serves a clear physiological role in cellular defense mechanisms and may have potential therapeutic applications. Several studies have also shown the importance of the roles of CO in the different body systems including: the nervous, immune, respiratory, reproductive, gastrointestinal, kidney, and liver systems.
The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important stress response pathway for preservation of internal homeostasis. CO has the ability to modulate the activity of the HPA axis in response to different stressors either by inhibition or stimulation. So the present study was performed to investigate the effect of modifying endogenous CO production on some aspect of stress response. The drugs selected for this work included: hemin, the HO inducer and zinc mesoporphyrin, the HO inhibitor. The type of stress used is cold restraint stress (CRS).
The present study was conducted on 36 adult male rats weighing 200-250 gram. Rats were left to accommodate to the environment for two weeks before the start of the experiments. Rats were randomly classified into the following groups:
I. Non- stressed Groups:
In which rats were left freely wandering in their cages at room temperature, and were included in the following groups (six rats in each group):
2. Control group; in which rats received no medication.
2. Hemin treated group; each rat received hemin at a dose level of 25 mg/kg body weight, intraperitoneal injection twice weekly for 2 weeks.
3. Zinc mesoporphyrin treated group; each rat received zinc mesoporphyrin at a dose level of 2.5 μmol /Kg body weight/day, intraperitoneal injection for 5 days.
II. Cold Restraint-Stressed (CRS) Groups:
In which each rat was restrained by fixing the four limbs to a wooden board and placed in a refrigerator at 4OC for 3 hours. The door of the refrigerator was opened every 0.5 hour for inspection and follow up. The rats were included in the following groups (six rats in each group):
4. CRS group; in which rats received no medication before cold restrained.
5. Stressed hemin treated group (Hemin +CRS); each rat received hemin at a dose level of 25 mg/kg body weight, intraperitoneal injection twice weekly for 2 weeks before the exposure to CRS.
6. Stressed zinc mesoporphyrin treated group (Zinc mesoporphyrin + CRS); each rat received zinc mesoporphyrin at a dose level of 2.5 μmol /Kg body weight/day, intraperitoneal injection for 5 days before the exposure to CRS.
The rats were then anesthetized by light ether anesthesia. Blood samples were aspirated from the heart and collected in tubes containing heparin as anticoagulant and then centrifuged and the supernatant plasma was kept at the refrigerator at -20OC for analysis of catecholamines, cortisol, lipid profile, glucose, and adrenocoricotrophic (ACTH) hormone. Their supra-renal glands were removed and dissected well from the surrounding mesentery and kept at the refrigerator at -20OC for analysis of catecholamines.
The results obtained clearly demonstrated that:
•Adminstration of hemin, the HO inducer significantly decreased the plasma ACTH, cortisol, epinephrine, cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) and produced insignificant changes in plasma glucose, norepinephrine, dopamine and adrenal catecholamines in all groups (non-stressed and stressed).
•Treatment of rats with zinc mesoporphyrin, the HO inhibitor significantly increased the plasma ACTH, catecholamines, cortisol, cholesterol, triglyceride, LDL, HDL and adrenal catecholamines without significant change in plasma glucose in all groups.
•In rats subjected to CRS there were significant elevations of adrenal catecholamines, plasma ACTH, cortisol, catecholamines, glucose, cholesterol, triglyceride, LDL, and HDL.