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  • Title: Protective effects of compound ammonium glycyrrhizin, L‑arginine, silymarin and glucurolactone against liver damage induced by ochratoxin A in primary chicken hepatocytes.
    Author: Yu Z, Wu F, Tian J, Guo X, An R.
    Journal: Mol Med Rep; 2018 Sep; 18(3):2551-2560. PubMed ID: 30015927.
    Abstract:
    Ochratoxin A (OTA) is a mycotoxin that is produced by fungi in improperly stored food and animal feed. It exhibits nephrotoxic, hepatotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic and carcinogenic effects in laboratory and farm animals. In the present study, the hepatotoxicity of OPA was investigated in chicken primary hepatocytes. On this basis, the cytoprotective effects of compound ammonium glycyrrhizin (CAG), L‑arginine (L‑Arg), silymarin (Sil) and glucurolactone (GA) were investigated in vitro. Hepatocytes were treated with OTA, which resulted in a significant decrease in cell viability and increases in serum aspartate transaminase and alanine transaminase activities, as determined by an MTT assay and commercial kits, respectively. Furthermore, following OTA treatment, the levels of hepatic antioxidants, such as superoxide dismutase and glutathione, were decreased, and the lipid peroxidation product malondialdehyde was increased, compared with the control group. However, pretreatment with CAG, L‑Arg, Sil and GA significantly ameliorated these alterations and Sil exerted the optimum hepatoprotective effect. The apoptotic rates were measured by flow cytometry and the results revealed that OTA increased cell apoptosis. The four types of hepatoprotective compounds employed in the present study decreased the apoptosis rate and significantly reversed OTA‑induced increases in the mRNA expression levels of caspase‑3, which was determined by reverse transcription‑quantitative polymerase chain reaction. Furthermore, B‑cell lymphoma‑2 (Bcl‑2) mRNA expression was increased in OTA‑treated cells when pretreated with CAG, L‑Arg, Sil and GA. However, no alterations in the mRNA expression of Bcl‑2‑associated X were observed in the L‑Arg and GA groups, compared with the OTA‑only group. These results indicate that OTA may exhibit hepatotoxicity in chickens and that CAG, L‑Arg, Sil and GA may protect the liver against this via anti‑oxidative and antiapoptosis mechanisms. In addition, CAG and GA are likely to mediate their effects through the mitochondrion‑dependent apoptosis pathway; however, the exact hepatoprotective mechanism of L‑Arg and GA require further investigation. Therefore, CAG, L‑Arg, Sil and GA are potential candidates for the prevention and treatment of chicken liver injury.
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