Taniguchi M, Yasutake A, Takedomi K, Inoue K
Division of Food and Nutrition, Nakamura Gakuen University, Fukuoka, Japan.
Arch Toxicol. 1999 Apr-May;73(3):141-6. doi: 10.1007/s002040050598.
To investigate oxidative effects of N-nitrosodimethylamine (NDMA) on the liver, rats were challenged by the reagent with a dose range of 10 to 40 mg/kg. With lower dose levels, protective responses were prominent, such as elevation of the hepatic glutathione and metallothionein (MT) levels. Increased activities were also evident of gamma-glutamylcysteine synthetase, glucose-6-phosphate dehydrogenase (G6PD), and malic enzyme. In the high dose range, however, toxic responses, such as increases in lipid peroxide levels in liver and serum, and glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and ketone bodies in serum became marked. Some of the protective responses became less marked at the highest dose. Catalase and glutathione peroxidase activities in the liver were also inhibited by NDMA treatment. On the other hand, when NDMA was injected as a series of doses (10 mg/kg on four separate occasions), the effects were less marked, and the hepatic levels of MT and lipid peroxide remained unchanged even after the 4th injection. Only the increase in G6PD activity was more marked after four times repeated injection than after a single injection. These results suggest that oxidative and hepatotoxic effects of NDMA are more moderate when given in repeated doses than in a single dose. In contrast to the liver, elevation of MT levels was the only detectable change in the kidney.
为研究N-亚硝基二甲胺（NDMA）对肝脏的氧化作用，用剂量范围为10至40mg/kg的该试剂对大鼠进行攻击。在较低剂量水平时，保护反应显著，如肝脏谷胱甘肽和金属硫蛋白（MT）水平升高。γ-谷氨酰半胱氨酸合成酶、葡萄糖-6-磷酸脱氢酶（G6PD）和苹果酸酶的活性也明显增加。然而，在高剂量范围内，毒性反应变得明显，如肝脏和血清中脂质过氧化物水平升高，以及血清中谷氨酸草酰乙酸转氨酶（GOT）、谷氨酸丙酮酸转氨酶（GPT）和酮体增加。一些保护反应在最高剂量时变得不那么明显。NDMA处理也抑制了肝脏中的过氧化氢酶和谷胱甘肽过氧化物酶活性。另一方面，当以一系列剂量（每次10mg/kg，共四次）注射NDMA时，影响较小，即使在第四次注射后，肝脏MT水平和脂质过氧化物水平仍保持不变。只有G6PD活性在四次重复注射后比单次注射后增加更明显。这些结果表明，NDMA重复给药时的氧化和肝毒性作用比单次给药时更为缓和。与肝脏不同，MT水平升高是肾脏中唯一可检测到的变化。
