Abnormal zinc and copper metabolism in hepatic steatosis.

Abnormal Zinc and Copper metabolism were studied in rats with tetracycline-induced fatty liver and compared with normal rats. The present work recorded decreased serum zinc concentration with increased copper concentration in the tetracycline-injected rats. The results also showed that the liver and heart zinc were significantly decreased; meanwhile it was observed that the concentration of zinc in the kidney tissue of fatty liver rats was significantly raised in comparison with those of normal rats. Histopathological studies of the kidney tissue showed degenerative changes in the tables with areas of focal necrosis. Renal tubular necrosis in such cases is largely caused by the toxic degradation products of tetracycline metabolism. The kidney lesion together with impaired gastrointestinal absorption contributed to the hypozincaemia observed in the present results. Although the present data showed a significant reduction in serum zinc and significant rise in plasma insulin in the fatty liver rats there was nonsignificant correlation between the two variables as compared with the normal rats. The positive correlation between serum zinc concentration and reduced high-density lipoprotein cholesterol (HDL-C) emphasizes the role of zinc deficiency in atherosclerotic disease in fatty liver.

Mechanism of insulin resistance and hyper-insulinemia in fatty liver.

Hyperinsulinemia and insulin resistance are common features seen in most liver diseases. The present study was carried out on an experimental model of fatty liver (tetracycline induced) in albino rats. Significantly elevated levels of both peripheral plasma insulin and plasma glucose concentrations were recorded in both the fasting state and after an oral glucose intake in the tetracycline-treated rats. The presence of hyperinsulinemia accompanying hyperglycemia is considered a sign of insulin resistance. Peripheral insulin resistance has been proved in this work by the reduced "A" value which refer to the peripheral insulin activity (sensitivity) in fatty liver rats compared to normal rats. The hyperinsulinemia recorded here was due to pancreatic hypersecretion and not a result of reduced hepatic degradation. Hypersecretion of insulin was clearly determined by measuring the level of immunoreactive insulin (IRI) in pancreatic vein which exhibited a significant rise in tetracycline-treated rats, and there was a positive correlation between the pancreatic venous and peripheral venous insulin in the basal state and after 30 min. of oral glucose administration. Hepatic degradation of insulin was not a cause as evidenced by First: the amount of insulin secreted and insulin consumed were significantly higher in fatty liver rats than normal controls. Second: the whole body extraction ratio or insulin degradation was not significantly different in the tetracycline-treated rats from the normal rats. The present data suggests that insulin resistance and hyperinsulinemia underlie the observed metabolic disturbances that characterize fatty liver disease.

Relationship between schistosomicidal drug efficacy, gonadal steroid hormonal changes and state of disease immunopathology in murine schistosomiasis mansoni.

The schistosomicidal efficacy of praziquantel (2 x 500 mg/kg), oxamniquine (1 x 100 mg/kg) and combined one-third the curative dose of each of them (333 mg/kg praziquantel + 33 mg/kg oxamniquine), were correlated to gonadal steroid hormonal changes and state of disease immunopathology, in mice infected with 100 Schistosoma mansoni (S. mansoni) cercariae. Maximum efficacy recorded with combination regimen particularly 4 weeks after treatment, was accompanied by maximum reduction in granuloma volume (65%), least fall in testosterone level (-56.2 and -60.2% in male and female mice respectively) and increased progesterone level (+33.9 and +81.5% in male and female mice respectively). These findings revealed a potentiated effect of combination therapy on mature infection and the possible involvement of gonadal steroid hormones in affecting the efficacy of schistosomicidal drugs and state of disease immunopathology.