Kobayashi M, Takahashi T, Taguchi K, Hirayama Y, Tsuchida S, Yamaki T, Yano M, Uchida T
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1989 Jan;93(1):17-27. doi: 10.1254/fpj.93.17.
The preventive effect of KZ-1026 on acute liver injury induced by CCl4 in rats was evaluated histochemically, enzyme-histochemically and ultrastructurally. Rats that received 50% CCl4 (2 ml/kg) intraperitoneally were sacrificed at 3, 7 and 24 hr. Remarkable reductions in hepatic glycogen, RNA and G-6-Pase activity were observed in the centrilobular area at 3 hr, and ballooned cells appeared in the mid-zone at 7 hr. At 24 hr, the above histochemical parameters in the hepatocytes of the centrilobular area and mid-zone were extensively reduced, while the number of ballooned cells in the mid-zone was increased. KZ-1026 (200 mg/kg) was given orally at 24 and 4 hr before, simultaneously with or 3 hr after CCl4 treatment, and each rat was sacrificed at 24 hr after CCl4 administration. Pretreatment with KZ-1026 24 hr before CCl4 administration prevented reduction of RNA, glycogen and G-6-Phase activity, as well as disruption of rER and proliferation of sER due to CCL4 toxicity. This preventive effect of KZ-1026 was reduced by posttreatment; however, only the decrease in cytoplasmic RNA was well prevented. These results suggested that KZ-1026 is protective against CCl4-induced acute liver injury.
采用组织化学、酶组织化学及超微结构方法，评估KZ - 1026对四氯化碳诱导的大鼠急性肝损伤的预防作用。腹腔注射50%四氯化碳（2 ml/kg）的大鼠分别在3小时、7小时和24小时处死。在3小时时，中央小叶区域肝糖原、RNA和葡萄糖 - 6 - 磷酸酶活性显著降低，7小时时中区出现气球样细胞。在24小时时，中央小叶区域和中区肝细胞的上述组织化学参数大幅降低，而中区气球样细胞数量增加。在四氯化碳处理前24小时、4小时、同时或处理后3小时口服给予KZ - 1026（200 mg/kg），每只大鼠在四氯化碳给药后24小时处死。在四氯化碳给药前24小时用KZ - 1026预处理可防止RNA、糖原和葡萄糖 - 6 - 磷酸酶活性降低，以及因四氯化碳毒性导致的粗面内质网破坏和滑面内质网增殖。KZ - 1026的这种预防作用在处理后减弱；然而，只有细胞质RNA的减少得到了很好的预防。这些结果表明，KZ - 1026对四氯化碳诱导的急性肝损伤具有保护作用。
