Effect of recombinant growth hormone [rh-GH] on glycerol induced acute renal failure [ARF] in rats

Experimental studies showed that acute uremia is characterized by reduced GH and IGF-l messenger RNA expression and is manifested as resistance to human rh-GH. However the administration of high doses of several anabolic agents including rh-GH have been proposed as a potential therapy for several catabolic conditions including acute renal failure [ARF]. Therefore this study was conducted to reveal the renoprotective and ameliorating effects of GH on glycerol-induced ARF in rats, by exploring its effects on generating IGF-l, decreasing ROS, improving kidney function and its effect on the generation of the vasodilator nitric oxide [NO]. The present study included four groups of albino rats, the first group [control group] was injected with saline, the second group [AFR group], in which 50% of glycerol was injected intramuscularly [im]. The third group was injected with the vehicle of growth hormone and the fourth group was injected with rh-GH [2 mg/day] for 5 days subcutaneously [sc] 48 hr after induction of ARF. The results showed 3.79 and 4.09 folds increase in blood urea and serum creatinine, respectively for the ARF group compared to the control group. These values in group IV deceased by 79.5 and 49% after rh-GH hormone treatment compared to their controls [group III]. Also the increased mean value of plasma malondialdehyde [MDA] and deceased mean value of plasma nitric oxide [NO] in the ARF group as compared to controls were markedly corrected after rh-GH treatment. The greatly increased level of IGF-l after rh-GH injection suggests that it may be the actual player behind these ameliorating effects of rh-GH on glycerol-induced ARF in rats. The therapeutic uses of rh-GH in ameliorating the effects of ARF that has already happened [as early as possible] and its protective effects in expected cases is therefore recommended

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

Role of angiotensin converting enzyme inhibitor on the functional changes in irradiated rats

Background: Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulosclerosis and/or tubulointerstitial fibrosis. Administration of Angiotensin-converting enzyme [ACE] inhibitor markedly abrogates the severity of radiation nephropathy and can prevent the functional changes that occur after irradiation

Objective: The present study was designed to test the efficacy of converting enzyme inhibition [enalapril] and its possible mechanistic basis in preventing functional changes in irradiated rats

Method: 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

Results: Irradiation induced significant elevations in the levels of blood urea nitrogen, serum creatinine, and serum activities of lactate dehydrogenase [LDH]; creatine kinase [CK]; alanine amino transferase [ALT]; and aspartate amino transferase [AST] compare to control values, indicative of renal, cardiac, and hepatic injury. Also there was an increase in the serum levels of triglycerides, total cholesterol, and LDL-cholesterol. On the contrary, HDL-cholesterol level was decreases. The heart, kidney and liver antioxidant enzymes including total glutathione peroxidase. [total-GPX], glutathione reductase [OR], 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 injury. It can be concluded that enalapril treatment of rats prior to irradiation was able to diminish the functional changes that occur after irradiation as evidenced by a beneficial decrease in all parameters determined in the sera of these rats, with an increase in the level of HDL-cholesterol and an amelioration of inhibition of antioxidant enzymes activities in the organs of these rats

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