Transcriptomic alterations induced by aflatoxin B1 and ochratoxin A in LMH cell line

Abstract

Aflatoxin B1 (AFB1) and ochratoxin A (OTA), which are toxic metabolites of ubiquitously occurring molds, show diverse toxicological effects such as hepatotoxicity, genotoxicity, and immunotoxicity in human and animals. Despite poultry show sensitivity to AFB1 and OTA, the mechanism of these mycotoxins in chickens has not been fully investigated. Here, we aimed to elucidate the molecular mechanism induced by AFB1 and/or OTA in chicken hepatic cells using transcriptomic analysis. Aflatoxin B1 and OTA induced cytotoxic effects in a dose-dependent manner at 48 h after exposure. Furthermore, correlation effect indicated an antagonism between the 2 toxins. The mRNA sequencing of AFB1-treated or OTA-treated chicken hepatocarcinoma and functional analysis revealed the pathways that were commonly regulated by both mycotoxins, especially PPAR signaling, focal adhesion, and MAPK signaling. Based on these findings, a possible hypothesis is that AFB1 and OTA have similar toxic mechanisms and compete for some steps in the chicken liver, and it is expected that the mycotoxins would have antagonistic effects. In addition, genes identified through transcriptome analysis provide candidates for further study of AFB1 and OTA toxicity and targets for efforts to improve the health of chickens exposed to mycotoxins.

Keywords

• aflatoxin
• ochratoxin
• hepatoxicity
• chicken liver
• transcriptomics