Luteolin alleviates aflatoxinB1-induced apoptosis and oxidative stress in the liver of mice through activation of Nrf2 signaling pathway

Abstrakt

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.

Autorzy

Shahid A. Rajput
Shahid A. Rajput
Aftab Shaukat
Aftab Shaukat
Kuntan Wu
Kuntan Wu
Imran R. Rajput
Imran R. Rajput
Dost M. Baloch
Dost M. Baloch
Rana W. Akhtar
Rana W. Akhtar
Muhammad A. Raza
Muhammad A. Raza
Ashraf Albrakati
Ashraf Albrakati
Attalla F. El-Kott
Attalla F. El-Kott
Mohamed M. Abdel-Daim
Mohamed M. Abdel-Daim
artykuł
Antioxidants
Angielski
2021
10
8
1268
otwarte czasopismo
CC BY 4.0 Uznanie autorstwa 4.0
ostateczna wersja opublikowana
w momencie opublikowania
2021-08-09
100
7,675
0
35