Combined effects of aflatoxin B1 and deoxynivalenol on the expression of glutathione redox system regulatory genes in common carp

Abstract

The purpose of the present study was to evaluate the short‐term effects of aflatoxin B1 (AFB1) and deoxynivalenol (DON) exposure on the expression of the genes encoding the glutathione redox system glutathione peroxidase 4a (gpx4a), glutathione peroxidase 4b (gpx4b), glutathione synthetase (gss) and glutathione reductase (gsr) and the oxidative stress response‐related transcription factors Kelch‐like ECH‐associated protein 1 (keap1) and nuclear factor‐erythroid 2 p45‐related factor 2 (nrf2) in liver, kidney and spleen of common carp. During the 24‐hr long experiment, three different doses (5 µg AFB1 and 110 µg DON; 7.5 µg AFB1 and 165 µg DON or 10 µg AFB1 and 220 µg DON/kg bw) were used. The results indicated that the co‐exposure of AFB1 and DON initiated free radical formation in liver, kidney and spleen, which was suggested by the increase in Nrf2 dependent genes, namely gpx4a, gpx4b, gss and gsr. Expression of keap1 gene showed upregulation after 8 hr of mycotoxin exposure, and also upregulation of nrf2 gene was found in kidney after 8 hr of exposure, while in the liver, only slight differences were observed. The changes in the expression of the analysed genes suggest that level of reactive oxygen species reached a critical level where other signalling pathway was activated as described by the hierarchical model of oxidative stress.

Individual and Combined Effects of Aflatoxin B1 and Sterigmatocystin on Lipid Peroxidation and Glutathione Redox System of Common Carp Liver

“…The RNA sample preparation, qPCR procedure, and relative RNA abundance qualification were conducted without modifications as previously described [ 39 ]. Primers ( Table 6 ) for the glutathione peroxidase 4a, 4b ( gpx4a, gpx4b ), glutathione synthetase ( gss ), glutathione reductase ( gsr ), nuclear factor-erythroid 2 p45-related factor 2 ( nrf2 ), kelch-like ECH-Associated protein 1 ( keap1 ) and reference gene β-actin were chosen based on the literature [ 51 , 52 , 53 ].…”

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity

“…It was presented that AFB1 leads to decreased expression of Nrf2 and its downstream gene HO-1, simultaneously with oxidative stress and pro-inflammatory cytokines response in broiler chickens (Li et al 2019b). Induction of Nrf2 signalling pathway was also observed in common carp (Kövesi et al 2020b). The experiment conducted on human hepatocytes L02 cells revealed that caveolin-1 (CAV-1) interacts with Nrf2 in response to oxidative stress caused by AFB1 to trigger apoptosis in cells (Xu et al 2020).…”

Research progress in toxicological effects and mechanism of aflatoxin B1 toxin

“…Exposure to AFB 1 and DON synergistically increased oxidative stress in the liver, kidney, and spleen of carp by upregulating Nrf2. Interestingly, ROS generation occurred earlier in the kidneys compared to the liver and spleen ( Kövesi et al, 2020 ). In conclusion, the nephrotoxicity of AFB 1 is mainly manifested as oxidative stress induced by p21, L-proline, Nrf2 and other genes.…”