Bagchi M, Bagchi D, Hassoun E A, Stohs S J
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178.
Int J Exp Pathol. 1994 Jun;75(3):197-202.
The possible role of reactive oxygen species in the toxicity of smokeless tobacco (ST) was explored. The effects of an aqueous smokeless tobacco extract (STE) at doses of 125, 250 and 500 mg STE/kg in rats on the induction of hepatic mitochondrial and microsomal lipid peroxidation and the incidence of hepatic nuclear DNA damage 24 hours post treatment were examined. Dose-dependent increases of 1.8, 2.3 and 4.4-fold in mitochondrial and 1.5, 2.1 and 3.6-fold in microsomal lipid peroxidation occurred at 125, 250 and 500 mg STE/kg, respectively, relative to control values. At these same three doses of STE, 1.3, 1.4 and 2.7-fold increases in hepatic DNA single-strand breaks occurred relative to control values. STE administration also resulted in significant increases in excretion of urinary metabolites. Urinary excretion of the four lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) was monitored by HPLC for 72 hours after treatment of rats with 125 and 250 mg STE/kg. Increases occurred in the excretion of the four lipid metabolites at every dose and time point with maximum increases in the excretion of all lipid metabolites being observed between 12 and 24 hours post treatment. The results suggest the involvement of an oxidative stress in the toxicity of STE.
探讨了活性氧在无烟烟草（ST）毒性中的可能作用。研究了大鼠经125、250和500 mg STE/kg剂量的无烟烟草水提取物（STE）处理24小时后，对肝线粒体和微粒体脂质过氧化的诱导作用以及肝细胞核DNA损伤的发生率。相对于对照值，在125、250和500 mg STE/kg剂量下，线粒体脂质过氧化分别增加了1.8、2.3和4.4倍，微粒体脂质过氧化分别增加了1.5、2.1和3.6倍。在相同的这三个STE剂量下，肝DNA单链断裂相对于对照值分别增加了1.3、1.4和2.7倍。STE给药还导致尿代谢产物排泄显著增加。在用125和250 mg STE/kg处理大鼠后，通过高效液相色谱法监测72小时内四种脂质代谢产物丙二醛（MDA）、甲醛（FA）、乙醛（ACT）和丙酮（ACON）的尿排泄情况。在每个剂量和时间点，四种脂质代谢产物的排泄均增加，在处理后12至24小时观察到所有脂质代谢产物排泄增加最多。结果表明氧化应激参与了STE的毒性作用。
