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

Shahid Ali Rajput,Papliński Rafał,Mohamed M Abdel-Daim,Attalla F El-Kott,Agnieszka Najda,Dost Muhammad Baloch,Muhammad Asif Raza,Aftab Shaukat,Ashraf Albrakati,Kuntan Wu,Imran Rashid Rajput,Rana Waseem Akhtar

doi:10.3390/antiox10081268

Abstract

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.

Highlights

Aflatoxins are one of the most dangerous mycotoxins, produced mainly by Aspergillus flavus and Aspergillus parasiticus and usually found in agricultural environments and food commodities [1]
The protective effects of luteolin (LUTN) on the growth of mice exposed to aflatoxin
During the entire experimental period, the group exposed to Aflatoxin B1 (AFB1) recorded the (p < 0.05) lowest ADG and average dailytreatment feed intake (ADFI) in the comparison of CON, LUTN and AFB1 + LUTN groups, respectively

Summary

Introduction

Aflatoxins are one of the most dangerous mycotoxins, produced mainly by Aspergillus flavus and Aspergillus parasiticus and usually found in agricultural environments and food commodities [1]. Even low levels of aflatoxins in the diet can be harmful to human health [2,3]. Approximately 4.5 billion people are in danger of being exposed to aflatoxins, which cause 4.6–28.2% of all occurrences of hepatocellular carcinoma worldwide [4,5]. Aflatoxin B1 (AFB1 ) is the most potent liver carcinogen among the aflatoxins, and it has been categorized as a Class I carcinogen by the International. Agency for Research on Cancer (IARC) [6]. AFB1 is reported to cause severe health issues, including growth retardation, hepatotoxicity, neurotoxicity, teratogenicity, mutagenicity and immunotoxicity in humans and animals [7,8,9]. Previous research has shown that reactive oxygen species (ROS)

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