Tumor necrosis factor-alpha [TNF-alpha] in glutathione[GSH]-depleted rats. a possible link to impaired glucose metabolism

reated with the glutathione depleting agent, allyl alcohol [A1A1] [1 mmol/kg] was found to induce a marked increase in serum TNF-alpha 45 minutes post treatment. This increase is suggested to play a critical role in the development of impaired glucose metabolism and glucose intolerance in A1A1-treated rats. Impaired glucose metabolism was evidenced by the significant increase in serum creatinine, urea and blood urea nitrogen accounting for accelerated glycolysis and breakdown of creatinine phosphate. These are the metabolic consequences of the activation of a back up system for the generation of ATP when the primary energy forming pathway is impaired. Meanwhile, the present data show a significant decrease in the serum levels of triglycerides and cholesterol in A1A1-treated rats that was accompanied with a concomitant increase in their liver levels indicating the development of fatty livers in these rats. Due to the strong link between TNF-alpha and the GSH status and to the well established role of TNF-alpha: in causing insulin resistance, which is potentiated by fat accumulation in different tissues, it is concluded that the combination of TNF-alpha overproduction, GSH depletion and lipid accumulation in the liver caused by A1A1 treatment, cooperate making cells more sensitive to A1A1 poisoning, therefore, imposing a potent negative impact on glucose metabolism. Added to the deleterious effects of TNF-alpha, enhanced lipid peroxidation observed in A1A1- treated rats suggests possible alterations in the rates of glucose transport and metabolism which may further contribute to AlAl-induced impairment in glucose metabolism. Finally, the selective effect of TNF-alpha in inhibiting insulin secretion give an additional support to its hypothesized role in initiating glucose intolerance in GSH-depleted rat

Possible protection of vitamin E and alpha-lipoic acid against early changes in alloxan diabetic rats

Diabetes mellitus is a chronic syndrome affecting carbohydrate, fat, protein and nucleic acid metabolism. The current study was undertaken to elucidate the possible role of vitamin E and alpha lipoic acid in combination as an antioxidant and a biological membrane stabilizer in the protection against early complication of diabetes. Administration of alloxan [125 mg/kg wt, i.p.] to rats resulted in hyperglycemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia, increase in plasma levels of urea, blood urea nitrogen [BUN], creatinine, uric acid as well as pancreatic thiobarbituric acid reactive substances [TBARS] and glutathione [GSH] content of both liver and retina. These changes were accompanied with significant decrease in plasma total protein, tumor necrosis factor alpha [TNF alpha], hepatic catalase activity [CAT], and TBARS level of both liver and retina as compared to control group. However, plasma levels of calcium ions [Ca+2] and nitric oxide [NO] as well as pancreatic GSH content were not changed. On the other hand, the daily treatment of the diabetic rats with antioxidant mixture attained a reduction in plasma levels of glucose, cholesterol, triglycerides, total lipids, urea, BUN, creatinine, uric acid, TNF alpha, pancreatic TBARS level as well as GSH content of both liver and retina. In contrast, the daily treatment caused an increase in plasma levels of insulin, total proteins, hepatic CAT activity and pancreatic GSH content as compared to diabetic rats. However, plasma levels of Ca+2 and NO as well as TBARS content of both liver and retina were not affected. In conclusion, it is obvious from the present study results that early stage [two weeks] of diabetes induce deteriorate changes in carbohydrate, lipid, protein and nucleic acid metabolism accompanied with increasing of oxidative stress in pancreas as compared to both of liver and retina. Moreover, the data of present study indicated the effective role of vitamin E and alpha lipoic acid combination in combating the oxidative stress via its improvement to metabolism of carbohydrates, lipids, proteins and nucleic acids in addition to its free radical-scavenging and antioxidant properties