Sanny C G, Mahoney A J, Kilmore M A, Rymas K
Oklahoma College of Osteopathic Medicine and Surgery, Tulsa 74107.
Alcohol Clin Exp Res. 1988 Oct;12(5):622-4. doi: 10.1111/j.1530-0277.1988.tb00253.x.
Dogs were used as nonrodent animal models to study the in vivo effects of disulfiram on hepatic aldehyde dehydrogenase (ALDH) activity. Dogs were treated with disulfiram either intraperitoneally or orally (100 mg/kg/day for 2 days followed by 40 mg/kg/day for 3 days). Liver biopsies from control and treated animals were fractionated by differential centrifugation and the subcellular fractions were analyzed for ALDH activity. Significantly less activity was observed in cell homogenates from treated animals (20-50% of control activity per gram of liver). The majority of loss in activity was accounted for by a decrease in ALDH activity in the soluble fraction of the cell (12-30% of control activity) and in the mitochondrial fraction (23-30% of control activity). Activities at both high (5 mM) and low (50 microM) acetaldehyde concentrations were affected. The subcellular distribution of ALDH activity and in vivo inhibition by disulfiram in dogs is different from that reported for rats.
狗被用作非啮齿类动物模型，以研究双硫仑对肝脏醛脱氢酶（ALDH）活性的体内影响。狗通过腹腔注射或口服双硫仑进行治疗（100毫克/千克/天，持续2天，随后40毫克/千克/天，持续3天）。对对照组和治疗组动物进行肝脏活检，通过差速离心法进行分级分离，并对亚细胞组分进行ALDH活性分析。在治疗组动物的细胞匀浆中观察到的活性显著降低（每克肝脏的活性为对照组的20 - 50%）。活性损失的大部分是由于细胞可溶性组分中ALDH活性的降低（为对照组活性的12 - 30%）以及线粒体组分中ALDH活性的降低（为对照组活性的23 - 30%）。高（5毫摩尔）和低（50微摩尔）乙醛浓度下的活性均受到影响。狗体内ALDH活性的亚细胞分布以及双硫仑对其的体内抑制作用与大鼠的报道不同。
