Department of Biology, Institute of Science, Giresun University, Giresun, Turkey.
Department of Biology, Faculty of Science and Art, Giresun University, Giresun, Turkey.
Sci Rep. 2023 Jan 23;13(1):1237. doi: 10.1038/s41598-023-28546-8.
Aflatoxin M (AFM) is a type of mycotoxin detected in milk or dairy products from animals consuming contaminated feed. In this study, the toxicity mechanism of AFM and 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 AFM. The toxic effects of AFM and the protective properties of quercetin were investigated using physiological, biochemical and cytogenetic parameters. The genotoxic mechanism of AFM and the protective role of quercetin were investigated by molecular docking, which is an in silico model. As a result, 16 mg/kg b.w AFM administration 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 AFM administration 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. AFM also caused genotoxicity by inducing micronucleus (MN) and chromosomal abnormalities (CAs) in bone marrow tissue. It has been determined that AFM, 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 AFM were 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 AFM were 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.
黄曲霉毒素 M（AFM）是一种在动物食用受污染饲料后，从牛奶或乳制品中检测到的真菌毒素。在这项研究中，研究人员研究了 AFM 的毒性机制以及槲皮素的保护作用在白化小鼠中。为此，将小鼠分为 6 组，并用槲皮素和 AFM 喂养。使用生理、生化和细胞遗传学参数研究了 AFM 的毒性作用和槲皮素的保护特性。通过分子对接研究了 AFM 的遗传毒性机制和槲皮素的保护作用，分子对接是一种计算机模型。结果表明，16mg/kg b.w AFM 给药导致体重、器官指数、肾脏和肝脏重量严重变化，以及肝肾功能抗氧化/氧化平衡恶化。AFM 给药后肝脏和肾脏中谷胱甘肽水平下降，丙二醛（MDA）水平升高，表明氧化应激诱导。丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平升高，这是肝损伤的指标，以及血清中血尿素氮（BUN）和肌酐水平升高，这是肾损伤的指标，证实了这两种器官的损伤。AFM 通过诱导骨髓组织中的微核（MN）和染色体异常（CAs）也表现出遗传毒性。已经确定，由于其断裂剂和变构剂的作用，AFM 通过与 DNA 相互作用引起 CAs。槲皮素通过改善肝、肾组织，使血清参数水平部分正常化，以及严重减少 MN 和 CAs，提供了显著的保护作用。在 50mg/kg b.w 槲皮素应用中，对双着丝粒染色体形成的最高保护率为 74.1%。槲皮素与黄嘌呤氧化酶和一氧化氮合酶的相互作用在计算机上通过抑制常数在 283.71-476.17 nM 的范围内进行了确定。这些相互作用会导致酶活性的变化，从而减少细胞中的氧化负荷，从而使槲皮素提供保护。随着槲皮素给药剂量的增加，AFM 引起的所有毒性作用均呈剂量依赖性降低，这种保护作用与槲皮素通过抑制产生自由基的酶来减少氧化负荷有关。随着槲皮素给药剂量的增加，AFM 引起的所有毒性作用均呈剂量依赖性降低，这种保护作用与槲皮素通过抑制产生自由基的酶来减少氧化负荷有关。
