Antioxidants suppress nitrofurazone-induced proliferation of hepatocytes.
On administration to rats at a subtoxic dose, the antibiotic nitrofurazone (NF) has been shown to increase hepatocyte DNA synthesis and liver weight in a dose-dependent manner, with no histological or biochemical evidence of cell damage or necrosis. Free radicals are implicated in NF metabolism, as well as in the DNA synthesis or cell proliferation induced by a number of other chemicals. In the present study, NF was given alone or concomitantly with the antioxidants N-acetylcysteine or cyanidanol. Antioxidants prevent the effects of free radicals. Co-administration decreased hepatocyte proliferation to the same level as the control. This suppression of NF-induced hepatocyte proliferation by antioxidants therefore strongly suggests that free radical production is involved in this process.
Ito
Kyoko
K
Safety Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan. itou@yamanouchi.co.jp
Kajikawa
S
S
Aisuke
Nii
N
Hanada
T
T
Doi
Kunio
K
D000111:Acetylcysteine / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009583:Nitrofurazone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms
D000891:Anti-Infective Agents, Local; D000975:Antioxidants; D002392:Catechin; D001973:Bromodeoxyuridine; D000111:Acetylcysteine; D009583:Nitrofurazone