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Protective Effects of Astaxanthin on Ochratoxin A-Induced Liver Injury: Effects of Endoplasmic Reticulum Stress and Mitochondrial Fission–Fusion Balance

Yiting Zou, Shiyi Zhang, Jian Yang, Chen Qin, Bo Jin, Zhenyu Liang, Shuhua Yang, Lin Li, Miao Long

2024Toxins15 citationsDOIOpen Access PDF

Abstract

Ochratoxin A (OTA), a common mycotoxin, can contaminate food and feed and is difficult to remove. Astaxanthin (ASTA), a natural antioxidant, can effectively protect against OTA-induced hepatotoxicity; however, its mechanism of action remains unclear. In the present study, we elucidate the protective effects of ASTA on the OTA-induced damage of the endoplasmic reticulum and mitochondria in broiler liver samples by serum biochemical analysis, antioxidant analysis, qRT-PCR, and Western blot analysis. ASTA inhibited the expressions of ahr, pxr, car, cyp1a1, cyp1a5, cyp2c18, cyp2d6, and cyp3a9 genes, and significantly alleviated OTA-induced liver oxidative damage (SOD, GSH-Px, GSH, MDA). Furthermore, it inhibited OTA-activated endoplasmic reticulum stress genes and proteins (grp94, GRP78, atf4, ATF6, perk, eif2α, ire1, CHOP). ASTA alleviated OTA-induced mitochondrial dynamic imbalance, inhibited mitochondrial division (DRP1, mff), and promoted mitochondrial fusion (OPA1, MFN1, MFN2). In conclusion, ASTA can decrease OTA-induced oxidative damage, thereby alleviating endoplasmic reticulum stress and mitochondrial dynamic imbalance.

Topics & Concepts

Endoplasmic reticulumMFN1MFN2Oxidative stressMitochondrial fissionMitochondrionUnfolded protein responseGlutathioneBiologymitochondrial fusionCell biologyPharmacologyBiochemistryMitochondrial DNAGeneEnzymeRedox biology and oxidative stressSelenium in Biological SystemsEndoplasmic Reticulum Stress and Disease