Indole-3-carbinol inhibits lipid deposition and promotes autophagy in hyperlipidemia zebrafish larvae

This study investigated the protective effect of I3C in hyperlipidemia zebrafish larvae and early life stage toxicity of I3C on zebrafish embryos/larvae. Zebrafish larvae were fed with 4% high-cholesterol diet (HCD) and treated with I3C 2.5μmol/L and 5μmol/L for two weeks. Confocal image analysis, oil Red O staining were used to analysis vascular lipid accumulation and western blotting was used to evaluate possible mechanics. In addition, zebrafish embryos were treated with I3C for 96 hours to assess the general toxicity and cardiotoxicity. We found that lipid deposition on vasculature was dose-dependently decreased in the I3C treated groups as compared with control group (47%, 23%, p<0.01). Moreover, we demonstrated that I3C inhibited lipid deposition by inducing autophagy, as identified by the enhancement of LC3-II, beclin-1, hVps34 and m-cathepsin D as well as by the reduction of P62, Bcl-2, Akt, p- Akt, mTOR, and p- mTOR in HCD fed zebrafish larvae (p<0.05). In summary, I3C shows protective effects on hyperlipidemia zebrafish larvae and maybe a promising multitarget drug in the prevention and protection against atherosclerotic.
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research