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

Aflatoxin B1 (AFB1) is a food contaminant metabolized mostly in the liver and leading to hepatic damage. Livestock species are differently susceptible to AFB1, but the underlying mechanisms of toxicity have not yet been fully investigated, especially in ruminants. Thus, the aim of the present study was to better characterize the molecular mechanism by which AFB1 exerts hepatotoxicity in cattle. The bovine fetal hepatocyte cell line (BFH12) was exposed for 48 h to three different AFB1 concentrations (0.9 µM, 1.8 µM and 3.6 µM). Whole-transcriptomic changes were measured by RNA-seq analysis, showing significant differences in the expression of genes mainly involved in inflammatory response, oxidative stress, drug metabolism, apoptosis and cancer. As a confirmatory step, post-translational investigations on genes of interest were implemented. Cell death associated with necrosis rather than apoptosis events was noted. As far as the toxicity mechanism is concerned, a molecular pathway linking inflammatory response and oxidative stress was postulated. Toll-Like Receptor 2 (TLR2) activation, consequent to AFB1 exposure, triggers an intracellular signaling cascade involving a kinase (p38β MAPK), which in turn allows the nuclear translocation of the activator protein-1 (AP-1) and NF-κB, finally leading to the release of pro-inflammatory cytokines. Furthermore, a p38β MAPK negative role in cytoprotective genes regulation was postulated. Overall, our investigations improved the actual knowledge on the molecular effects of this worldwide relevant natural toxin in cattle.

Section: Discussionsupporting

confidence: 88%

Section: Afb1 Cytotoxicity and Mechanism Of Cell Deathsupporting

confidence: 89%

Deepening the Whole Transcriptomics of Bovine Liver Cells Exposed to AFB1: A Spotlight on Toll-like Receptor 2

Iori

Pauletto

Bassan

et al. 2022

“…Moreover, the combination of AFB 1 and OTA can lead to less apparent hepatic and more severe kidney lesions, which may be a burden in achieving diagnosis [ 20 ]. This can be attributed to the fact that AFB 1 and OTA show weak cytotoxic effect in liver cell lines, when are in combination than alone, suggesting an antagonistic interaction [ 21 ]. In contrast, in most of the studies, AFs and OTA induced synergistic and/or additive interactions in mortality, body weight, feed intake, egg production, embryo abnormalities, and atrophy of lymphoid organs [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of a Novel Multicomponent Mycotoxin Detoxifying Agent in Amelioration of Mycotoxicosis Induced by Aflatoxin-B1 and Ochratoxin A in Broiler Chicks

Tsiouris

Tassis

Raj³

et al. 2021

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.

“…The genotoxic effect has been observed in vivo on mice [110]. Cytotoxic and/or genotoxic effects of AFB 1 have been reported in vitro on the leghorn male hepatoma (LMH) cell line [121], the liver hepatocellular carcinoma (HepG2) cell line [122], buffalo rat liver (BRL-3A) cells [123], bovine mammary epithelial (BME) cells [124], and the human keratinocyte (HaCaT) cell line [125]. Cytotoxicity on BME cells has also been observed in vitro in the case of AFM 1 [124].…”

Section: Recent Data On Aflatoxin Toxicitymentioning

confidence: 99%

“…For example, in the recent literature, the antagonistic effect on inducing cytotoxicity on the LMH cell line has been observed between AFB 1 and OTA [121]. On the contrary, these two mycotoxins, also in combination with zearalenone (ZEA), acted synergistically in negatively affecting the milk production, blood metabolism, and immune function of Laoshan goats [131].…”

Section: Toxicological Interactions Of Aflatoxins and Other Mycotoxinsmentioning

confidence: 99%

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

Pickova

Ostrý

Toman

et al. 2021

In the early 1960s the discovery of aflatoxins began when a total of 100,000 turkey poults died by hitherto unknown turkey “X” disease in England. The disease was associated with Brazilian groundnut meal affected by Aspergillus flavus. The toxin was named Aspergillus flavus toxin—aflatoxin. From the point of view of agriculture, aflatoxins show the utmost importance. Until now, a total of 20 aflatoxins have been described, with B1, B2, G1, and G2 aflatoxins being the most significant. Contamination by aflatoxins is a global health problem. Aflatoxins pose acutely toxic, teratogenic, immunosuppressive, carcinogenic, and teratogenic effects. Besides food insecurity and human health, aflatoxins affect humanity at different levels, such as social, economical, and political. Great emphasis is placed on aflatoxin mitigation using biocontrol methods. Thus, this review is focused on aflatoxins in terms of historical development, the principal milestones of aflatoxin research, and recent data on their toxicity and different ways of mitigation.