ABSTRACT
Insulin resistance predicts development of type 2 diabetes mellitus [DM]. Adipocytes release tumor Necrosis factor-alpha [TNF-alpha], and adiponectin. They modulate whole-body insulin sensitivity. The disturbance in the relationship between good and bad adipokines may cause insulin resistance. The renin-angiotensin aldosteron system [RAAS] plays a role in DM and the consequence of cardiovascular complications development. It is considered as a target for therapy. The present objective examined the relationship between renin angiotensin system and DM. There were, Group [1]: Normal non obese rats, Group [2]: Obese diabetic rats, Group [3]: Obese diabetic rats with telmisartan, Group [4]: Obese diabetic rats with enalapril, Group [5]: Obese diabetic rats with aliskiren. There was a significant increase in serum glucose, lipid profile [triglycerides [TGs], low-density lipoprotein cholesterol [LDL], total serum cholesterol [TC]], tumor Necrosis factor-alpha [TNF-alpha], malondialdehyde [MDA] and a significant decrease in adiponectin associated with minor changes in superoxide dismutase [SOD] activity in the obese diabetic rats. Administration of telmisartan, enalapril and or aliskiren caused a significant improvement in serum lipid profile and adiponectin, a minor improvement in SOD activity, a decrease in TNF- alpha and or MDA. Conclusion: Renin angiotensin blockers significantly improve the metabolism and oxidative dysfunctions in Type 2 DM and aliskiren may show a promising powerful therapy
ABSTRACT
Considerable evidence indicates that increased oxidative stress and induction of apoptosis signaled through the Fas pathway appear to play an important role in the pathogenesis of autoimmune diabetes. The present study aimed to detect the soluble Fas [sFas] as apoptotic marker and the total antioxidant capacity [TAC] in type 1 diabetes [T1D] and high-risk group children and whether it is altered by antioxidant vitamin supplement. Forty-five participants were included in the study and divided into three groups: group 1 comprised 15 children with new onset diabetes; group 2 included 15 diabetic children with long-standing diabetes; and group 3 comprised 15 individuals of patient's relatives. Serum levels of sFas and TAC were measured and compared between groups before and after antioxidant vitamin supplementation. The highest level of sFas was found in group 2 [2196.7 +/- 579 pg/ml], however, with no statistical significance; after vitamins supplementation, its level showed significant decrease to reach 1156.6 +/- 460.8 pg/ml [P = 0.01]. Similar tendency of serum Fas decrease was observed in the group of relatives after vitamins supplementation [2088.3 +/- 396.5 vs. 1426.7 +/- 140.9, P < 0.01]. TAC was significantly lower in group 2 than in the other two groups, and it showed a significant increase after vitamin intake [0.29 +/- 0.06 vs. 0.40 +/- 0.05 micromol/l, P < 0.05]. One month of treatment with antioxidants vitamins supplement increased the antioxidant activity in long-standing T1D children and resulted in significant reduction in sFas level, suggesting the importance of this therapeutics in reducing apoptosis changes in children with T1D
ABSTRACT
Acetaminophen is one of the most common pharmaceuticals associated with both intentional and accidental poisoning. Acetaminophen-induced hepatotoxicity is the most frequent cause of fulminate liver failure, and can have a mortality rate 90%. The present work aimed at the investigation of the possible effect of trimetazidine in preventing acetaminopheninduced hepatotoxicity and comparing it with the traditionally used N- acetyl cysteine for the same purpose. The present study was carried out on 40 mice. Mice were divided into 2 main groups. Group I: consisted of 10 animals considered as control group and received saline. Group II: consisted of 30 animals which were subdivided into 3 equal subgroups [10 mice/ subgroup] as follows: subgroup [IIA]: served as acetaminophen only treated group,in a dose of 500 mg/kg intragastrically. Subgroup [IIB]: acetaminophen treated mice treated with N-acetyl cysteine in a dose of 200mg/kg intragastrically one hour before administration of acetaminophen. Subgroup [IIC]: acetaminophen treated mice treated with trimetazidine in a dose of 20 mg/kg intragastrically one hour before administration of acetaminophen. Liver cell integrity was monitored by measurement of serum glutamate pyruvate transaminase [SGPT]. Glutathione [GSH] in blood and malondialdehyde [MDA] in serum were assessed. Liver cell integrity was also confirmed by histopathological examination for assessing the distribution and extent of cell death. Mice treated with acetaminophen only showed a significant increase in SGPTand MDA; and a significant reduction in GSH. Histopathologically, acetaminophen produce many grades of necro inflammatory lesions. Pre-administration of N-acetyl-Cystein or trimetazidine before acetaminophen treatment produced a significant reduction in SGPT and MDA, furthermore, it produced a significant increase in GSH level and also protected the liver against acetaminophin-induced injury. In conclusion, the present work demonstrated that trimetazidine ameliorates the acetaminophen induced lesion to a similar extent by N-acetyl-Cysteine