Contamination of Aflatoxins Induces Severe Hepatotoxicity Through Multiple Mechanisms

Abstract

Aflatoxins (AFs) are commonly contaminating mycotoxins in foods and medicinal materials. Since they were first discovered to cause “turkey X” disease in the United Kingdom in the early 1960s, the extreme toxicity of AFs in the human liver received serious attention. The liver is the major target organ where AFs are metabolized and converted into extremely toxic forms to engender hepatotoxicity. AFs influence mitochondrial respiratory function and destroy normal mitochondrial structure. AFs initiate damage to mitochondria and subsequent oxidative stress. AFs block cellular survival pathways, such as autophagy that eliminates impaired cellular structures and the antioxidant system that copes with oxidative stress, which may underlie their high toxicities. AFs induce cell death via intrinsic and extrinsic apoptosis pathways and influence the cell cycle and growth via microribonucleic acids (miRNAs). Furthermore, AFs induce the hepatic local inflammatory microenvironment to exacerbate hepatotoxicity via upregulation of NF-κB signaling pathway and inflammasome assembly in the presence of Kupffer cells (liver innate immunocytes). This review addresses the mechanisms of AFs-induced hepatotoxicity from various aspects and provides background knowledge to better understand AFs-related hepatoxic diseases.

Penthorum Chinense Pursh Extract Alleviates Aflatoxin B1-Induced Liver Injury and Oxidative Stress Through Mitochondrial Pathways in Broilers

“…AFB1 destroys the normal structure of hepatocytes and mitochondria, subsequently altering the antioxidant system. Furthermore, autophagy eliminates impaired cellular structures and apoptosis is initiated by liver hepatocytes to maintain liver function; however, it also causes hepatotoxicity (7)(8)(9). The metabolic and toxic effects of AFB1 are principally observed in liver tissues, and previous studies have suggested that hepatic cell apoptosis leads to liver damage in poultry.…”

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation

“…Naturally occurring AFs (AFB 1 , AFB 2 , AFG 1 , and AFG 2 ) act as strong carcinogens, thus they are assigned into Group 1 "carcinogenic to humans" by the International Agency for Research on Cancer (IARC) [84,105]. Apart from their carcinogenicity, they have been reported to have mainly hepatotoxic, genotoxic, mutagenic, teratogenic, immunosuppressive, nephrotoxic, and cytotoxic effects [106][107][108][109].…”

Obesity promotes Fumonisin B1 toxicity and induces hepatitis

“…Furthermore, the effects of FB1 on liver damage and inflammation were consistent with an inhibition of the wellknown pro-inflammatory and pro-apoptotic effects of sphingolipid species respectively such as S1P and sphingoïd bases (Molino et al, 2017;Riley et al, 2001). Therefore, the proinflammatory effects of FB1 observed in HFD-fed mice might have occurred as an indirect consequence of altered ceramide homeostasis (Chen et al, 2021). Alternatively, high FB1 exposure may exert toxic effects in hepatocytes that are independent of ceramide metabolism, but reflect a mechanism yet to be determined.…”

“…The most common symptoms are nephrotoxicity, hepatotoxicity (Terciolo et al, 2019), immunotoxicity (Devriendt et al, 2009;Halloy et al, 2005), and intestinal barrier function disturbances (Bouhet et al, 2006;Loiseau et al, 2007). To date, the known molecular mechanisms underlying FB1 toxicity are mostly related to its inhibitory effect on sphingolipid biosynthesis (Wang et al, 1991;Chen et al, 2021). Indeed, FB1 and sphingoid long-chain bases share similar structural backbone features.…”