Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver regeneration and function of hepatic mitochondria in partially hepatectomized rats.
Effects of 1-[(2-Thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363), a hepatoprotective compound, on liver regeneration, liver nucleic acid levels, mitochondrial respiration activity and hepatic energy metabolism after partial hepatectomy (OPE) in rats were studied. The liver regeneration rate was significantly increased in rats administered 100 mg/kg of KF-14363 for 6 d as compared with the control group administered vehicle. The serum glucose level in rats administered 100 mg/kg of KF-14363 measured 3 h after OPE (OPE 3 h) was significantly higher than that in rats administered vehicle (group A) and the serum insulin level in the KF-14363 group was more than double that of group A. KF-14363 also significantly increased liver nucleic acid levels in OPE rats. In mitochondrial function experiments, KF-14363 (100 mg/kg) was orally administered 2 h after OPE. Three hours after OPE (1 h after KF-14363 administration), state 3 respiration was significantly higher in the OPE 3 h + KF-14363 group than in the OPE 3 h + water group. The adenosine diphosphate/oxygen (ADP/O) ratio was also significantly higher in the OPE 22 h (22 h after OPE) + KF-14363 group than in the OPE 22 h + water group. On hepatic energy metabolism, KF-14363 increased adenosine diphosphate and triphosphate levels. Total adenine nucleotide level in the OPE 3 h + KF-14363 group was significantly higher than that in the OPE 3 h + water group. Adenylate energy charge (AEC) was slightly decreased in the OPE 3 h + water group and significantly decreased in the OPE 22 h + water group than in the corresponding sham group.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshitake
I
I
Pharmaceutical Research Laboratories of Kyowa Hakko Kogyo Co., Shizuoka, Japan.
Ohishi
E
E
Kubo
K
K
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D006498:Hepatectomy; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*
D001552:Benzazepines; D001786:Blood Glucose; D007328:Insulin; D013844:Thiazoles; C074412:KF 14363; D012313:RNA; D004247:DNA