No regional differences of cytochrome P450 expression in the liver of Cynomolgus monkeys (Macaca fascicularis).

Non-human primates are frequently used in toxicological studies the result of which are extrapolated to humans, but background data on drug metabolism ability among monkeys derived from different countries has not been published, especially on the key enzyme, cytochrome P450 (CYP450). We assessed the amounts of hepatic CYP450 obtained from cynomolgus monkeys of different ages and from different countries in this study. There were no regional differences of total P450 content, as well as major CYP450 isozymes (CYP 1A, 2A, 2B, 2C, 2D, 2E1 and 3A4) in cynomolgus monkeys by westernblot analysis.

Amelioration of the beta-cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments.

Background: In our recent report, probucol treatment ameliorated glucose intolerance and increased the insulin-positive area in the pancreas of streptozotocin (SZ)-induced diabetic APA hamsters. The data suggested that the beneficial effects of probucol treatment on beta-cell function might result from its additive effect as an antioxidant. Here, we examined the antioxidant effects on the beta-cell function in SZ-induced diabetic APA hamsters treated with three different agents, N-acetyl-L-cysteine (NAC), aminoguanidine (AG) and pyridoxamine (PM).

Protective effects of probucol treatment on pancreatic beta-cell function of SZ-induced diabetic APA hamsters.

To clarify whether oxidative stress is involved in the pathogenesis of islet lesions of diabetic animals, the effects of probucol (PB), an antioxidant and anti-hyperlipidemia agent, on the islets in streptozotocin (SZ)-induced diabetic APA hamsters in the acute and chronic phases of diabetes were examined. The control (CB group) and diabetic (SZ group) hamsters were treated with PB (1% in the diet) for 4 weeks from several days after SZ injection as the acute diabetic group, or 8 weeks from 6 weeks after SZ injection as the chronic diabetic group. Glucose tolerance test revealed that PB treatment decreased the high serum glucose level after glucose injection in the diabetic APA hamsters in the acute diabetic phase.

D-galactosamine induced hepatocyte apoptosis is inhibited in vivo and in cell culture by a calcium calmodulin antagonist, chlorpromazine, and a calcium channel blocker, verapamil.

Studies were conducted in C57BL/6N Crj male mice and in cultured hepatocytes to clarify the relationship between galactosamine (GaIN) induced apoptosis and [Ca2+]i kinetics. Chlorpromazine (CPZ), a Ca(2+)-calmodulin antagonist, and verapamil (VR), a Ca(2+)-channel blocker each inhibited GaIN-induced DNA fragmentation and the appearance of apoptotic bodies. The kinetics of calcium uptake were evaluated using a calcium analyzer with the acetoxymethyl ester of fura-PE3 (fura-PE3/AM, 2.

The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers.

The effect of chronic hyperglycemia and hyperlipidemia induced by streptozotocin (SZ) on the expression of P450 in the liver of APA hamsters was studied in this experiment. No effect on the total activity of P450 was seen in SZ-induced diabetic hamsters throughout the experimental period. At 1 and 6 months after SZ-injection, the levels of CYP1A, 2C6, and 3A of SZ-injected hamsters were much lower than those of age-matched control hamsters.

Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia.

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller.