Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants

Attalla F. El-Kott¹  Kuntan Wu²  Shahid Ali Rajput³  Dost Muhammad Baloch⁴  Ashraf Albrakati⁵  Mohamed M. Abdel-Daim⁶  Papliński Rafał⁷  Agnieszka Najda⁷  Imran Rashid Rajput⁸  Rana Waseem Akhtar⁹  Muhammad Asif Raza⁹  Aftab Shaukat^1,10 

[1] Biology Department, Faculty of Science, King Khalid University, Abha 61421, Saudi Arabia;Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China;Department of Animal Nutrition and Feed Sciences, College of Animal Science, South China Agricultural University, Guangzhou 540642, China;Department of Biotechnology, Lasbela University of Agriculture Water and Marine Science, Uthal 89250, Pakistan;Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia;Department of Vegetable Crops and Medicinal Plants, University of Life Sciences in Lublin, 50A Doświadczalna Street, 20-280 Lublin, Poland;Faculty of Veterinary and Animal Science, Lasbela University of Agriculture Water and Marine Science, Uthal 89250, Pakistan;Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture, Multan 66000, Pakistan;National Center for International Research on Animal Genetics, Breeding and Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China;

关键词: aflatoxin B₁;    luteolin;    oxidative stress;    apoptosis;    liver injury;    Nrf2 signaling pathway;   

DOI  :  10.3390/antiox10081268

来源: DOAJ

【 摘 要 】

Aflatoxin B₁ (AFB₁), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB₁-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B₁ (AFB₁). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B₁ + 50 mg/kg BW luteolin (AFB₁ + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB₁ exposure. LUTN ameliorated AFB₁-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB₁-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB₁ exposure. Our results indicated that LUTN effectively alleviated AFB₁-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB₁-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

【 授权许可】

Unknown