[Preventive effect of KZ-1026 on acute liver injury induced by CCl4 in rats: histochemical, enzyme-histochemical and ultrastructural studies].
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.
Kobayashi
M
M
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Takahashi
T
T
Taguchi
K
K
Hirayama
Y
Y
Tsuchida
S
S
Yamaki
T
T
Yano
M
M
Uchida
T
T
D000208:Acute Disease; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006651:Histocytochemistry; D007659:Ketones / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000627:therapeutic use*
D007659:Ketones; D008112:Liver Glycogen; D013876:Thiophenes; D012313:RNA; C059615:2-(1,3-dithiolan-2-ylidene)-1-phenyl-1,3-butanedione; D005952:Glucose-6-Phosphatase