Effect of hyperhomocysteinemia on erythrocyte function and its impact on erythropoiesis in experimental rats

The current work was conducted to study the possible effect of hyperhomocysteinemia [HHcy] on some erythrocytic functions as a cause of anemia and its impact on erythropoietin [EPO] release in experimental rats. Forty adult male albino rats were divided into two main groups, the control group [Group I] and the hyperhomocysteinemic group [HHcy] [Group II]. Hyperhomocysteinemia was induced by subcutaneous injection of DL- homocysteine at a dose of 100 mg/kg/day for 4 weeks. At the end of the fourth week each main group was subdivided into two subgroups, [Ia] control, [Ib] Hypoxic-control [IIa] and HHcy, [IIb] Hypoxic-HHcy. Hypoxia was induced by a single intra-peritoneal injection of desferrioxamine [200 mg/kg] 22 hours before decapitation. Whole blood was used for determination of erythrocytic fragility, hematological parameters, reticulocyte percentage. Homocysteine, erythropoietin [EPO], urea and creatinine were estimated in plasma. Erythrocytes were used for estimation of lipid peroxidation, G6PDH activity and membrane separation for deten-nination of Na[+] K[+] ATPase enzymatic activity. Homocysteine, EPO and creatinine plasma levels, and reticulocyte% and erythrocytic lysis in addition to erythrocyte lipid peroxidation were all significantly higher, while G6PDH and Na[+] K[+]- ATPase enzymatic activities were significantly lower in the HHcy group as compared to the control group. A significant positive correlation was found between total Hcy plasma levels and erythrocyte lipid peroxidation. EPO plasma levels showed a significant increase in response to hypoxic stimulation in the control group, while blunted response was observed in the HHcy group. It could be concluded that disturbance in erythrocyte membrane and enzymatic functions in HHcy increases the susceptibility of RBCs to hemolysis and reduces its life span. Hyperhomocysteinemia also impacts EPO release to hypoxic stimulation which may be due to damaging effect of HHcy on renal cells

Role of oxytocin as regulator of leptin secretion and its relation to biochemical markers [OPG and SRANKL] of bone resorption and formation

Increasing evidences demonstrated many new targets for the hypothalamic hormone oxytocin [OT] supporting the presence of a central neuroendocrine and/or humoral factors that control bone remodeling. The present study was carried out to test the effect of OT on serum leptin level and on the regulation of skeletal homeostasis through measurement of serum levels of osteoprotogerin OPG [secreted glycoprotein of the tumour necrosis receptor superfamily], sRANKL [soluble decoy receptor activator of nuclear factor kappa filigand], calcium and phosphorus. Fifty adult male albino rats used in this study. They were divided into three groups: group I which was subdivided into 3 subgroups, subgroup IA untreated control, IB injected with DM SO [0.16 ml/kg, b.wt x 6 weeks], 1C injected with DMSO [0.08 ml/kg b.wt for 12 weeks]. II OT treated [40 micro/kg b.wt x6 weeks] group. Ill OT [8 micro/kg b.wt x 12 weeks] group. The results obtained showed very high significant increase in OPG level in group [II] compared with subgroups I A and IB and high significant increase of OPG in group [III] compared with subgroup 1C. On the other hand, non significant change was detected in serum levels of sRANKL. As regards serum leptin, a high significant increase was found in group II as compared with subgroups IA and IB and a high significant increase was detected in group [III] compared with IA and 1C subgroups. Serum calcium and phosphorus levels showed very high significant decrease in group [II] compared with IA and IB subgroups and high significant decrease in group [HI] compared with subgroup IA. Also, significant increase in OPG/sRANKL ratio in group [II] compared with IA subgroup. A negative correlation between sRANKL and OPG/sRANKL ratio was obtained in both OT treated groups.The OPG and sRANKL levels obtained in OT treated rats favor increased osteoblast over osteoclast activity and may explain, in part, the imbalance in bone remodeling in favor of bone formation. 'The rise in OPG serum level is probably a homeostatic mechanism to limit bone loss. We can say that leptin should be reappraised as an indicator of energy supplies available for homeostasis, which now includes bone remodeling. We can conclude that the stimulating effect of OT on serum leptin together with increased OPG synthesis indicate anabolic effect on osteoblastic cells to support bone formation and indicate the important role of OPG in bone remodeling and it may be useful for the treatment of osteoporosis associated with increased osteoclast function. OT and leptin can now be added to the array of bone modulating signalling molecules

Dysfunctional nitric oxide and 8-epi-prostaglandin F2alpha synthesis in healthy smokers

Background: Cigarette smoking, a major cardiovascular risk factor, has been shown to be associated with impaired endothelium- dependent vasodilatation [EDV]. Nitric Oxide [NO] being a primary vasodilator produced by endothelial cells, its production is probably affected by cigarette smoking. Cigarette smoke contains superoxide anions and a great number of other reactive oxygen species [ROS], the accumulation of which brings about oxidative damage of endothelial cells. A free radical catalyzed isomers of arachidonic acid [8-epi- PGF2infinity] is a potent vasoconstrictor and serves as a marker of oxidative stress

Objective: To evaluate the level of serum [NO] and urinary 8-epi- PGF2infinity in mild, moderate, and heavy smokers and to correlate their levels with urinary cotinine which is considered a sensitive markers of exposure to nicotine of tobacco smoke

Subjects: 20 heavy smokers, 20 moderate smokers, 20 mild smokers, and 20 controls were the material of the present study

Results: The present study revealed significant increase in urinary 8-epi- PGF2infinity in smokers compared to control subjects. Also significant increase was found in urinary 8-epi- PGF2infinity in heavy compared with moderate smokers. However, there was a significant decrease in serum [NO] in the same two groups as compared to controls. Positive correlation for urinary 8-epi- PGF2infinity and negative correlation for serum [NO] as compared to urinary cotinine were detected. It may be concluded that concentration of 8-epi- PGF2infinity and cotinine in the urine as well as NO in the sera of smokers might give more accurate information about ROS which play an important role in the pathogenesis of many diseases affecting the physiological functions of body systems

Association between serum OPG/s rankl system and leptin with aging in male rats

Increasing evidences have suggested the association between serum leptin and bone formation. Osteoprotegerin [OPG], an osteoblast derived regulator of bone resorption and formation binds with soluble receptor activator of nuclear factor Kappa beta ligand [sRANKL] on osteoclast surface -which binds to its cognate receptor RANK on the osteoclast precursor. Thus, OPG/RANKL/RANK system controls the balance in bone formation and resorption. This study is designed to evaluate whether the OPG/sRANKL system and leptin levels are modified with aging and how they are related to bone and aortic changes. Three groups of rats were selected according to age, 4 months old [Group I], 12 months old [Group II] and 24 months old [Group III]. Serum levels of OPG, sRANKL, leptin, calcium and phosphorus [in sera and aortic extracts] were determined. Histopathological examination of rat femur and aorta from each group was also done. ANOVA test revealed significant difference between the three groups. The aged group [Group III] had higher calcium levels in sera and aortic extracts, serum phosphorus, serum sRANKL, leptin with increased sRANKL/OPG ratio. However OPG was significantly decreased in the same group in comparison to the other 2 groups. A significant negative correlation between serum OPG and sRANKL/OPG ratio [r = -0.879, p < 0.001] and body weight [r = -0.763, p < 0.01] and positive correlation between leptin and sRANKL/OPG ratio [r = 0.734, p < 0.01] and Ca aortic extract [r = 0.844, p < 0.01]. The disruption of OPG/sRANKL system and leptin with old age due to deficient OPG, high serum sRANKL and leptin resistance would represent a link between arterial calcification and bone resorption that are mostly present in the elderly

protective role of the angiotensin-converting enzyme inhibitor enalapril against gamma radiation induced organ toxicity in the rat

The present study was designed to evaluate the radioprotective efficacy of the angiotensin-converting enzyme inhibitor enalapril and the possible mechanisms of this radioprotection. This included the ability of prophylactic enalapril treatment to prevent or retard gamma radiation-induced organ toxicity and to protect tissue' antioxidant enzymes in the rat. Prior to irradiation rats were randomized to groups receiving enalapril or no treatment, in addition to a control group of non-irradiated, non-treated rats. Enalapril was administered intraperitoneally [0.1 mg/ kg body weight / day], 4 weeks before and 12 weeks after irradiation. Both groups were exposed to a single dose of 7GY gamma radiation. Irradiation induced significant elevations in the levels of blood urea nitrogen and serum creatinine and serum activities of lactate dehydrogenase [LDH], creatine kinase [CK], alanine amino transferase [ALT] and aspartate amino transferase [AST] compared to control values, indicative of renal, cardiac and hepatic injury. Also there was an increase in the serum levels of triglycerides, total cholessterol and LDL-cholesterol. On the contrary, HDL-cholesterol level was decreased. The heart, kidney and liver antioxidant enzymes including total glutathione peroxidase [total-GPX], glutathione reductase [GR] and superoxide dismutase [SOD] activities were inhibited, while malondialdehyde [MDA] level in these organs was elevated, indicative of increased lipid peroxidation. These data confirm the role of oxidative stress in radiation-induced organ toxicity and points to the possible antioxidative mechanisms of the radioprotective action of enalapril, which might be mediated by improving the balance between reactive oxygen species and antioxidant enzymes. Moreover, the beneficial effect of enalapril on serum lipid profile is suggested to be an additional mechanism of radioprotection

Effect of the converting enzyme inhibitor [Captopril] and its interaction with the calcium antagonist [Verapamil] on lipid metabolism

The effect of a converting enzyme inhibitor [captopril] and its interaction with a calcium antagonist [verapamil] on lipid metabolism was studied. A daily dose of captopril [1 mg/200 g body weight] for 3 weeks was given to 8 rats, another group of 8 rats was given the same daily dose of captopril together with a daily dose of verapamil [125 mug/200 g body weight] for 3 weeks. At the end of the 3 weeks investigation of the differences in lipid patterns was done. Captopril alone caused significant increase in total cholesterol and triglycerides, but in the group treated with captopril and verapamil a less significant increase was revealed in total cholesterol. There were also significant changes in the different concentrations of lipoprotein fractions in the two groups. The verapamil was found to modulate the effect of captopril