Elucidating the toxicity mechanism of AFM2 and the protective role of quercetin in albino mice

Abstract

AbstractAflatoxin M2(AFM2) is a type of mycotoxin detected in milk or dairy products from animals consuming contaminated feed. In this study, the toxicity mechanism of AFM2and the protective effects of quercetin were investigated in albino mice. For this purpose, the mice were divided into 6 groups and the groups were fed with quercetin and AFM2. The toxic effects of AFM2and the protective properties of quercetin were investigated using physiological, biochemical and cytogenetic parameters. The genotoxic mechanism of AFM2and the protective role of quercetin were investigated by molecular docking, which is an in silico model. As a result, 16 mg/kg b.w AFM2administration caused serious changes in body weight, organ index, kidney and liver weight, and deterioration of antioxidant/oxidant balance in liver and kidney organs. The decrease in glutathione levels along with an increase in malondialdehyde (MDA) levels in the liver and kidney after AFM2administration indicates that oxidative stress is induced. The increases in alanine transaminase (ALT) and aspartat transaminase (AST) levels, which are indicators of liver damage, and the increases in serum levels of blood urea nitrogen (BUN) and creatinine, which are indicators of kidney damage, confirm the damage in both organs. AFM2also caused genotoxicity by inducing micronucleus (MN) and chromosomal abnormalities (CAs) in bone marrow tissue. It has been determined that AFM2, which exhibits genotoxicity as a result of its clastogenic and aneugenic effects, causes CAs by interacting with DNA. Quercetin provided significant protection by improving liver and kidney tissues, partial normalization in serum parameter levels, and severe reductions in MN and CAs. The highest protection was determined as 74.1% against dicentric chromosome formations in 50 mg/kg b.w quercetin application. The interaction of quercetin with xanthine oxidase and nitric oxide synthase enzymes was determined in silico with an inhibition constant in the range of 283.71–476.17 nM. These interactions cause changes in the activity of enzymes, reducing the oxidative load in the cell, and in this way, quercetin provides protection. All toxic effects induced by AFM2were decreased with quercetin administration dose-dependently, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the free radical-producing enzyme. All toxic effects caused by AFM2were decreased with quercetin administration in a dose-dependent manner, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the enzyme that produces free radicals.