Kawashima Y, Kozuka H
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Toxicology. 1992;71(1-2):151-60. doi: 10.1016/0300-483x(92)90062-j.
The possibility of using cytosolic long-chain acyl-CoA as a parameter to measure the response of liver to peroxisome proliferators was studied. A subcutaneous (s.c.) injection of perfluorooctanoic acid (PFOA) to male Wistar rats caused an increase in activity of cytosolic long-chain acyl-CoA hydrolase. This increase in activity seems to be due to enzyme induction, since it was prevented by simultaneous administration of cycloheximide or actinomycin D with PFOA. The activity of cytosolic long-chain acyl-CoA hydrolase was increased in a dose-dependent manner by the administration of three peroxisome proliferators with diverse chemical structures: alpha-(p-chlorophenoxy)isobutyric acid (clofibric acid), 2,2'-(decamethylenedithio)diethanol (tiadenol) and PFOA. The increased activity produced by clofibric acid lasted throughout a 22-week treatment. A good correlation was found between the activities of cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation induced by the administration of the peroxisome proliferators. These results indicate that cytosolic long-chain acyl-CoA hydrolase is a suitable parameter for measuring the response of rat liver to challenges by peroxisome proliferators.
研究了使用胞质长链酰基辅酶A作为参数来衡量肝脏对过氧化物酶体增殖剂反应的可能性。给雄性Wistar大鼠皮下注射全氟辛酸(PFOA)会导致胞质长链酰基辅酶A水解酶活性增加。这种活性增加似乎是由于酶的诱导,因为同时给予环己酰亚胺或放线菌素D与PFOA可阻止其增加。通过给予三种具有不同化学结构的过氧化物酶体增殖剂:α-(对氯苯氧基)异丁酸(氯贝酸)、2,2'-(十亚甲基二硫代)二乙醇(替阿地诺)和PFOA,胞质长链酰基辅酶A水解酶的活性以剂量依赖性方式增加。氯贝酸产生的活性增加在整个22周的治疗过程中持续存在。发现胞质长链酰基辅酶A水解酶的活性与过氧化物酶体增殖剂给药诱导的过氧化物酶体β-氧化之间存在良好的相关性。这些结果表明,胞质长链酰基辅酶A水解酶是衡量大鼠肝脏对过氧化物酶体增殖剂挑战反应的合适参数。