Protective action of indole‐3‐acetic acid on induced hepatocarcinoma in mice

Abstract

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 À1 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.

Anti-Inflammatory and Anti-Oxidative Activity of Indole-3-Acetic Acid Involves Induction of HO-1 and Neutralization of Free Radicals in RAW264.7 Cells

“…In particular, ROS generated by macrophages stimulated by LPS may cause excessive inflammatory reactions, leading to tissue damage [28]. IAA was previously reported to exhibit free radical elimination effects [29,30]. Consistently, we found that treatment of macrophages with IAA obviously blocked the generation of ROS induced by LPS.…”

Hybrid Enzyme‐Polymeric Capsules/Mesoporous Silica Nanodevice for In Situ Cytotoxic Agent Generation

“…It can be oxidized by the enzyme horseradish peroxidase (HRP) producing cytotoxic compounds, mainly hydroxyl and reactive oxygen species (ROS), able to destroy human cancer cells by membrane and DNA damage . IAA is not easily oxidized by mammalian peroxidases and, therefore, it is well tolerated in humans and even presents positive effects such as an increase in the phagocytic capacity of neutrophils or antioxidant activity . Therefore, the necessity to avoid the premature release of the housed pro‐drug from the silica matrix is not as important as in the case of transporting conventional cytotoxic compounds.…”

Rapid burst of H2O2 by plant growth regulators increases intracellular Ca2+ amounts and modulates CD4+ T cell activation

“…In general, IAA is non-toxic to adult mice; however, administration of 500-1000 mg/kg during the mid-gestation period causes microencephaly in the fetus [25]. IAA administration (500 mg/kg) lowers the expression of antioxidant enzymes in the liver and is protective in a model of diethylenitrosoamine-induced hepatocarcinogenesis in mice [26]. The activation of IAA using peroxidase or UV medium wavelength light results in the production of cytotoxic oxidation products that is effective during tumor therapy [27].…”