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

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.

Tilapia skin peptides restore cyclophosphamide-induced premature ovarian failure via inhibiting oxidative stress and apoptosis in mice

“…Caspase-3 is activated into an activated form by proteolysis under the stimulation of a variety of apoptotic signals and then participates in apoptotic processes. 37 Here, we found that the ratio of Bcl-2/Bax was decreased, and the caspase-3 protein was increased by CP. Therefore, TSP inhibited the CP-induced intrinsic apoptosis in ovarian granulosa cells via keeping pre-existing Bcl-2 protein and inhibiting Bax overexpression, which in flip can suppress caspase-3 expression.…”

Alleviation of Oral Exposure to Aflatoxin B1-Induced Renal Dysfunction, Oxidative Stress, and Cell Apoptosis in Mice Kidney by Curcumin

“…AFB1 is the most toxic of many secondary metabolites produced by fungi, posing considerable health risks to people and animals due to its hepatotoxic, immunotoxic, carcinogenic, and teratogenic effects [ 30 , 31 , 32 ]. The role of oxidative stress associated with AFB1-mediated organ toxicity has been widely researched in animal models [ 11 , 33 , 34 ]. Among these studies, a great deal of attention has been devoted to the liver, which is the principal organ for AFB1 bioactivation.…”

“…This suggests that the kidney is also involved in the accumulation of toxin AFB1. Research has demonstrated that oxidative stress is a critical risk factor for AFB1 toxicity and that exposure to AFB1 raises contents of reactive oxygen species (ROS), which can impair cellular redox homeostasis, leading to oxidative stress-induced kidney injury [ 11 ]. Therefore, mitigation of oxidative stress is emphasized as an effective strategy to treat AFB1 nephrotoxicity.…”

Luteolin Alleviates Epithelial-Mesenchymal Transformation Induced by Oxidative Injury in ARPE-19 Cell via Nrf2 and AKT/GSK-3β Pathway

“…It also was reported that luteolin activates the Nrf2 pathway. For example, luteolin enhanced autophagy and antioxidative processes in both in vivo and in vitro models of intracerebral hemorrhage [ 32 ], protected heart tissues in STZ-induced diabetic mice through modulating Nrf2-mediated oxidative stress and NF- κ B-mediated inflammatory responses, and alleviates aflatoxin B 1 -induced apoptosis and oxidative stress in the liver of mice through activation of the Nrf2 pathway [ 33 ]. The current results showed that luteolin promoted nuclear translocation of Nrf2, upregulated the expressions of HO-1 and NQO-1, increased the activities of SOD and GSH-PX, and decreased intracellular levels of ROS and MDA, suggesting that luteolin activated the Nrf2 pathway, thereby improving the survival rate of oxidative damaged ARPE-19 cells.…”