Protective action of indole-3-acetic acid on induced hepatocarcinoma in mice.
In this study, we report the protective effects of IAA on diethylnitrosamine (DEN)-induced hepatocarcinogenesis. BALB/c mice received daily IAA at 50 (T(50)), 250 (T(250)), and 500 (T(500)) mg Kg(-1) per body mass by gavage for 15 days. At day 15, animals were administered DEN and sacrificed 4 h later. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed in sera. In addition, hepatomorphologic alterations, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), gene expression of antioxidant enzymes and DNA integrity were evaluated in the liver. IAA administration did not show any alterations in any of the parameters available, except for a reduction of the gene expression for antioxidant enzymes by 55, 56, 27, and 28% for SOD, CAT, GPx, and GR upon T(500), respectively compared with the control. Several hepatic alterations were observed by DEN exposure. Moreover, IAA administration at 3 doses was shown to provide a total prevention of the active reduction of CAT and GR induced by DEN exposure compared with the control. IAA at T(500) was shown to give partial protection (87, 71, 57, and 90% for respectively SOD, CAT, GPx, and GR) on the down-regulation of the enzymes induced by DEN and this auxin showed a partial protection (50%) on DEN-induced DNA fragmentation for both parameters when compared to DEN alone. This work showed IAA hepatocarcinogenesis protection for the first time by means of a DEN-protective effect on CAT and GR activity, and by affecting antioxidant gene expression and DNA fragmentation.
Mourão
Luciana R M B
LR
Laboratory of Biological Chemistry, Department of Basic Sciences, Faculty of Animal Science and Food Engineering (FZEA), University of Sao Paulo, Pirassununga, SP, Brazil.
Santana
Roberta S S
RS
Paulo
Lívia M
LM
Pugine
Silvana M P
SM
Chaible
Lucas M
LM
Fukumasu
Heidge
H
Dagli
Maria L Z
ML
de Melo
Mariza P
MP
D000410:Alanine Transaminase / Q000097:blood; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D053938:DNA Fragmentation; D004052:Diethylnitrosamine / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010088:Oxidoreductases / Q000097:blood; D010937:Plant Growth Regulators / Q000494:pharmacology*
D000477:Alkylating Agents; D000975:Antioxidants; D007210:Indoleacetic Acids; D010937:Plant Growth Regulators; D004052:Diethylnitrosamine; C030737:indoleacetic acid; D010088:Oxidoreductases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase