Quercetin protects the buffalo rat liver (BRL-3A) cells from aflatoxin B1-induced cytotoxicity via activation of Nrf2-ARE pathway
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Aflatoxin B1 (AFB1) is the most toxic mycotoxin widely presented in agricultural products, and the protective effect of quercetin (QUE), a natural antioxidant, against AFB1-induced cytotoxicity to the buffalo rat liver (BRL-3A) cells was investigated. With an IC50 of 23 μM, AFB1 induced a significant oxidative stress to BRL-3A cells evidenced by a dose-dependent reduction of mitochondria membrane potential (MMP), ATP content, and activities of endogenous antioxidant enzymes along with increased levels of reactive oxygen species (ROS) and lipid peroxidation biomarker of malondialdehyde (MDA). The activity of CYP1A2, the key enzyme to convert AFB1 to reactive AFB1 exo-8,9- epoxide, was also increased, which, probably in together with ROS, led to cell apoptosis with DNA fragmentation, chromatin condensation and increased lactate dehydrogenase release. After the BRL cells were pre-treated by low level QUE (2.5 and/or 5 μM) for 24 h and then exposed to AFB1, the activities of antioxidant enzymes including haeme oxygenase-1, glutathione S-transferase, superoxide dismutase, and the ratio of reduced to oxidised glutathione were significantly increased whereas the levels of intracellular ROS and MDA were reduced. The QUE pre-treatment also increased the levels of MMP, ATP and DNA integrity, and reduced the expression of apoptosis related genes ofBax andCaspase-3. The Western blotting study revealed increased content of phosphorylated Akt and nuclear NF-E2-related factor 2 (Nrf2), indicating an activation of Nrf2-ARE pathway in counteracting oxidative stress and cytotoxicity of AFB1. Thus, the QUE pre-treatment enhanced the anti-stress capacity of the cells through the activation of the Nrf2-ARE pathway, and QUE-based measures could be developed to ameliorate the toxicity caused by AFB1.
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Quercetin protects the buffalo rat liver (BRL-3A) cells from aflatoxin B1-induced cytotoxicity via activation of Nrf2-ARE pathway
In: World Mycotoxin JournalSearch for other papers by X. Wang in
Current site
Google Scholar
PubMed
Search for other papers by L. Li in
Current site
Google Scholar
PubMed
Search for other papers by G. Zhang in
Current site
Google Scholar
PubMed
Aflatoxin B1 (AFB1) is the most toxic mycotoxin widely presented in agricultural products, and the protective effect of quercetin (QUE), a natural antioxidant, against AFB1-induced cytotoxicity to the buffalo rat liver (BRL-3A) cells was investigated. With an IC50 of 23 μM, AFB1 induced a significant oxidative stress to BRL-3A cells evidenced by a dose-dependent reduction of mitochondria membrane potential (MMP), ATP content, and activities of endogenous antioxidant enzymes along with increased levels of reactive oxygen species (ROS) and lipid peroxidation biomarker of malondialdehyde (MDA). The activity of CYP1A2, the key enzyme to convert AFB1 to reactive AFB1 exo-8,9- epoxide, was also increased, which, probably in together with ROS, led to cell apoptosis with DNA fragmentation, chromatin condensation and increased lactate dehydrogenase release. After the BRL cells were pre-treated by low level QUE (2.5 and/or 5 μM) for 24 h and then exposed to AFB1, the activities of antioxidant enzymes including haeme oxygenase-1, glutathione S-transferase, superoxide dismutase, and the ratio of reduced to oxidised glutathione were significantly increased whereas the levels of intracellular ROS and MDA were reduced. The QUE pre-treatment also increased the levels of MMP, ATP and DNA integrity, and reduced the expression of apoptosis related genes ofBax andCaspase-3. The Western blotting study revealed increased content of phosphorylated Akt and nuclear NF-E2-related factor 2 (Nrf2), indicating an activation of Nrf2-ARE pathway in counteracting oxidative stress and cytotoxicity of AFB1. Thus, the QUE pre-treatment enhanced the anti-stress capacity of the cells through the activation of the Nrf2-ARE pathway, and QUE-based measures could be developed to ameliorate the toxicity caused by AFB1.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 118 | 93 | 10 |
| Full Text Views | 27 | 0 | 0 |
| PDF Views & Downloads | 14 | 2 | 0 |
