Snakehead-fish cell line, SSN-1 (Ophicephalus striatus) as a model for cadmium genotoxicity testing.

The purpose of this study is to evaluate the potential of snakehead-fish cell line (SSN-1 cells) derived from a striped snakehead (Ophicephalus striatus) as a model in the genotoxic assessment of cadmium (Cd). The first approach employed was to determine the contaminated Cd levels in commercial snakehead fish by the Graphite Atomic Absorption Spectrophotometer. In the second approach, the sensitivity of SSN-1 cells to cytotoxicity and genotoxicity of Cd was assessed by Trypan blue and micronucleus assays following 24, 48, and 72 h of incubation period. Exposure of SSN-1 cells to four increasing Cd concentrations ranging from 0.005 to 5 ppm for 72 h did not affect their survival as compared to the control cells. The Cd uptake by SSN-1 cells showed a concentration-dependent increase in intracellular Cd levels. Three non-cytotoxic Cd concentrations (0.05, 0.5, and 5 ppm) showed a concentration-dependent genotoxic effect, compared to relevant control cells. Both micronucleus frequencies and cadmium uptake levels by SSN-1 cells depended on exposure concentrations. These results showed that the SSN-1 cells are suitable for use as a model for in vitro Cd genotoxicity testing.

Effects of pyridoxine deficiency on the metabolism of N-nitrosodimethylamine in the rat.

The alteration in the metabolic activation of N-nitrosodimethylamine (NDMA) was investigated in the rat during dietary pyridoxine deficiency. The in vitro metabolism of NDMA by demethylase system was measured in both liver and kidney microsomes. The profile of the kidney enzyme appears similar to that of the liver indicating that at least two forms of isozymes with the low and the high Km's are present. Pyridoxine deficiency significantly increased the activity of NDMA-demethylase of both organs. The increase in the activity of NDMA-demethylase induced by dietary pyridoxine deficiency can be reversed by supplementation of pyridoxine (500 micrograms), i.p., daily for two consecutive days. The increase in the NADPH cytochrome c reductase activity was observed after 6 weeks on pyridoxine-deficient diet.

Alterations in dimethylnitrosamine-induced lethality and acute hepatotoxicity in rats during dietary thiamin, riboflavin and pyridoxine deficiencies.

The effects of dietary thiamin, riboflavin and pyridoxine deficiencies on dimethylnitrosamine-induced lethality and hepatotoxicity were investigated in the rat. Development of deficiencies was monitored by growth rate, food intake, ratio of liver weight to body weight and the biochemical parameters (thiamin diphosphate effects for thiamin deficiency, glutathione reductase activity coefficient for riboflavin deficiency and erythrocyte glutamate-oxaloacetate transaminase activity for pyridoxine deficiency). Thiamin deficiency slightly increased the acute toxicity of dimethylnitrosamine as observed by the lowering of the LD50 dose and the greater increase in the serum glutamate-oxaloacetate transaminase and serum glutamate-pyruvate transaminase levels. Riboflavin deficiency, on the other hand, slightly increased the LD50 dose of dimethylnitrosamine and resulted in less dimethylnitrosamine-induced damage to the liver. Pyridoxine deficiency did not affect the lethal dose nor significantly alter the transaminases levels.

The effect of indomethacin on hepatic drug-oxidizing capacity in the rat: trimethadione and antipyrine metabolism as an indicator.

In this study, trimethadione (TMO) and antipyrine were chosen as model drugs to investigate the extent of hepatic drug-oxidizing capacity. It was also studied whether pretreatment of rats with indomethacin affected the formation of antipyrine metabolite. Pretreatment with indomethacin in a dose of 5 mg/kg/d for 3 d did not change the serum half-life (T1/2), the total body clearance (CL), and the apparent volume of distribution (Vd) of TMO and antipyrine. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these parameters were significantly decreased as compared to controls except to Vd values in antipyrine kinetics in vivo. The contents of cytochrome P-450, and the activities of aminopyrine N-demethylase and aniline hydroxylase were not changed by 5 mg/kg/d for 3 d of indomethacin. However, in the rat treated with 8.5 mg/kg/d for 3 d of indomethacin, these enzyme activities were significantly decreased as compared to controls. The activities of heme oxygenase were significantly increased as compared to controls in the rat treated with 5 and 8.5 mg/kg/d for 3 d of indomethacin, in vitro. The excretions of 4-hydroxyantipyrine and 3-hydroxymethyl antipyrine were not changed in the rat treated with 8.5 mg/kg for 3 d of indomethacin as compared to controls, whereas the excretion of norantipyrine was significantly decreased. These results, together with the previous findings, indicate that indomethacin treatment inhibited N-demethylation pathway of TMO and antipyrine metabolism.