ABSTRACT
Atherosclerosis is considered one of the major causes of human morbidity and mortality all over the world. In this work, an attempt was done to investigate the possible role of nitric oxide [NO] on modulation of experimentally-induced atherosclerosis in male New Zealand White [NZW] rabbits. For this purpose, 64 male NZW rabbits were left for 2 weeks to acclimatize to laboratory conditions before being included in this experiment. Rabbits were then randomly classified into 8 equal groups. The first group [control, C] was fed commercial chow and the second group [atherosclerotic, A] was fed an atherogenic diet [containing 1% cholesterol]. The last 6 groups [VCA, AA, NSA, NA, PA and PNA groups] were fed the atherogenic diet in addition to the following respectively [vitamin C, L-arginine, Nigella sativa [NS], N-Nitro- L-arginine methyl ester [L-NAME], pravastatin and L-NAME with pravastatin]. The different feeding regimen and treatments were continued for 2 months. After 2 months, rabbits were killed to evaluate the severity of atherosclerosis and the effect of the different treatments given. The following parameters were assayed [plasma lipid profile, malondialdehydes [MDA], total antioxidant status [TAS] and nitrites; aortic tissue prostaglandin E[2][PGE[2]] and histological examination]. The atherogenic diet induced a significant increase in plasma total cholesterol [TC], triglycerides [TG], low density lipoprotein [LDL], high density lipoprotein [HDL] and MDA compared to C group. The TAS, nitrites and aortic PGE[2] were significantly decreased compared to control values. These atherogenic changes were reflected on the histopathological changes observed in aortic tissues from the A group. Vitamin C [500 mg/kg/day, orally] improved the atherogenic changes when given to atherosclerotic rabbits. There was a significant increase in TAS, nitrites and aortic PGE[2] associated with a significant decrease in MDA associated with improvement in the histopathological picture of aortic tissue of VCA group compared to A group. Administration of NS to atherosclerotic rabbits produced significant decrease in TC, TG, LDL and MDA and significant increase in HDL, TAS, nitrites and PGE[2] in NSA group compared with A group. These effects were associated with improvement in the histopathological picture of aortic tissue of NSA group compared with A group. L-arginine produced significant decrease in MDA and significant increase in TAS nitrites and PGE[2] in AA group compared with A group. In NA group, L-NAME aggravated atherosclerosis as evidenced by a significant increase in MDA, significant decrease in TAS, nitrites and PGE[2] and aggravation of the atherogenic changes in aortic tissue compared with A group. Pravastatin improved all atherogenic changes in PA group compared with A group. There were significant decrease in TC, TG, LDL and MDA with significant increase in HDL, TAS, nitrites and aortic PGE[2]. This protective effect of pravastatin was reflected on the histopathological picture of aortic tissue. In PNA group, L-NAME antagonized the protective effect of pravastatin. It was concluded that atherosclerosis is a multifactorial disease. The increase in free radicals [FR] and lipid peroxidation and the decrease in NO and PGE[2] are the main contributors of atherosclerosis. The antiatherogenic effects of pravastatin depend upon its plasma lipid lowering and antioxidant effects, in addition to increase intimal NO and PGE[2] production. L-NAME antagonized the antiatherogenic effects of pravastatin. The antiatherogenic effects of Nigel/a saliva and vitamin C depend mainly on their antioxidant action. Other mechanisms may contribute such as decrease in lipid profile [Nigella saliva] and increase in NO and PGE[2] production [Nigella saliva and Vitamin C]. These findings suggest that pravastatin is the most effective antiatherosclerotic agent followed by Nigella saliva and high dose of vitamin C. So, it is recommended that addition of Nigella saliva and/or antioxidant vitamins [such as vitamins C] to potentiate the antiatherogenic effects of pravastatin in atherosclerotic patients. This will also reduce the cost of treatment and side effects of drugs
ABSTRACT
The aim of the present work was to study the effect of sex difference on the development of gastric ulcer induced by cold restraint stress [CRS] in albino rats. The study is a trial to evaluate the role of gonadal sex hormones in the pathophysiologic mechanism of CRS-induced gastric mucosal lesions through either exclusion by gonadectomy or resupplementation by exogenous administration of sex hormones [testosterone, T; estrogen, E and progesterone, P]. For this purpose, 112 adult albino rats [48 males and 64 non pregnant females] weighing between 200-250 grams were used in this study. Male rats were randomly classified into 6 equal groups: control [CM], orchidectomized [OM], orchidectomized with testosterone supplementation [OT], stressed [SM], orchidectomized stressed [OSM] and orchidectomized stressed with testosterone supplementation [OST]. Female rats were randomly classified into 8 equal groups: Control [CF], ovariectomized [OF], ovariectomized with estrogen supplementation [OE], ovariectomized with progesterone supplementation [OP], stressed [SF], ovariectomized stressed [OSF], ovariectomized stressed with estrogen supplementation [OSE] and ovariectomized stressed with progesterone supplementation [OSP]. Bilateral gonadectomy was done; in either sexes; 2 weeks before exposure to CRS. Hormonal supplementations were given for 7 days by subcutaneous injections starting 2 weeks after gonadectomy in respected groups. In male rats, orchidectomy significantly increased gastric juice [GJ] volume and pH and gastric mucosal [GM] nitrates; while it significantly decreased GJ acidity in OM group compared with CM group. No ulcerative lesions were observed in CM and OM groups. Injection of T significantly decreased GJ volume and pH and GM nitrates but significantly increased GJ acidity in OT group compared with CM and OM groups. T administration induced ulcerative lesions in OT group achieving an ulcer index [UI] of 11.33. CRS significantly reduced GJ volume, pH and mucin concentration [MC] and GM nitrates while it significantly increased GJ acidity and pepsin concentration [PC] and GM peroxides in SM group compared with CM group. CRS induced ulcerative lesion in all male rats achieving an UI of 21.25 in SM group. Orchidectomy before exposure to CRS significantly increased GJ volume and pH and GM nitrates and significantly decreased GJ acidity and GM peroxides in OSM group compared with SM group. Orchidectomy exhibited considerable protection against CRS ulcer development achieving U1 of 16.5 and protective index [PI] of 22.4 % in OSM group. Injection of T significantly reduced GJ volume and pH and GM nitrates and significantly increased GJ acidity and GM peroxides in OST group compared with OSM group and aggravated the ulcerative lesions achieving an UI of 22.6 and PI of 36.97% in OST group. In female rats, ovariectomy, significantly increased GJ acidity and MC; while it significantly decreased GJ pH and PC and GM nitrate in OF group compared with CF group. No ulcerative lesions were observed in CF and OF groups. Administration of E significantly decreased GJ volume, acidity and MC; while it significantly increased GJ pH and PC and GM nitrates in OE group compared with both CF and OF groups. E induced ulcerative lesions achieving an UI of 9.66 in OE group. Administration of P significantly increased GJ volume, pH and MC and significantly decreased GJ acidity, and PC and GM nitrates in OP group compared with both CF and OF groups. No ulcerative lesions were observed in OP group. CRS significantly increased GJ acidity and PC and GM peroxides; while it reduced significantly GJ volume, pH and MC and GM nitrates in SF group compared with CF group. CRS induced ulceration in all rats achieving an UI of 18.3 in SF group. Ovariectomy before exposure to CRS significantly decreased GJ pH and PC and GM nitrates; while it significantly increased GJ volume, acidity and MC and GM peroxides in OSF group compared with SF group. Although GM lesions were noted in OSF achieving an UI of 13.3, ovriectomy exhibited protection against CRS-induced GM ulceration and the PI was 27.34. Administration of E significantly decreased GI volume, acidity and MC and GM peroxides; while it significantly increased GJ pH and PC and GM nitrates in OSE group compared with OSF group. E aggravated GM lesions in OSE group achieving an UI of 20.9 and PI of - 56.9. On the other hand, giving P significantly decreased GJ acidity and PC and significantly increased GJ volume, pH and MC in OSP group compared with OSF group. P imparted a protective effect against CRS GM lesions achieving an UI of 9.5 and PI of 12.6 in OSP
In conclusion, a gender difference in CRS-induced GM ulcer development has been found in the present work, being more predominant in male than in female albino rats. The male sex hormone; T is absolutely ulcerogenic and orchidectomy offered protection. The female sex hormone; P was absolutely protective, while E potentiated some aggressive factors and enhanced other protective mechanisms with the net effect being ulcerogenic. Ovariectomy offered gastric protection against CRS-induced ulceration. It is therefore, probable that the protective effect of P can restraint the ulcerogenic effect of E to some extent and therefore lower the gastric UI in females than in males