Protective role of curcumin in ameliorating AFB1-induced apoptosis via mitochondrial pathway in liver cells

Abstract

It is well documented that liver is the primary target organ of aflatoxin B (AFB) and curcumin proved to be effective against AFB-induced liver injury. In the present study, we investigated the preventive effects of curcumin against AFB-induced apoptosis through the molecular regulation of p53, caspase-3, Bax, caspase-9, Bcl-2 and cytochrome-C associated with mitochondrial pathway. Liver antioxidant levels were measured. The hallmarks of apoptosis were analysed by methyl green-pyronin-Y staining, transmission electron microscopy, RT-PCR and western blot. Results revealed that dietary curcumin ameliorated AFB-induced oxidative stress in a dose-dependent manner. Methyl green-pyronin-Y staining and transmission electron microscopy showed that AFB induced apoptosis and caused abnormal changes in liver cells morphology such as condensation of chromatin material, reduces cell volume and damaged mitochondria. Moreover, mRNA and protein expression results manifested that apoptosis associated genes showed up-regulation in AFB fed group. However, the supplementation of dietary curcumin (dose-dependently) alleviated the increased expression of the apoptosis associated genes at mRNA and protein level, and restored the hepatocytes normal morphology. The study provides an insight and a better understanding of the preventive mechanism of curcumin against AFB-induced apoptosis in hepatocytes and provide scientific basis for the therapeutic uses of curcumin.

Aflatoxins as a risk factor for liver cirrhosis: a systematic review and meta-analysis

“…In support of this hypothesis, several studies have demonstrated the potential for antioxidants to lower the risk of hepatotoxicity caused by exposure to the AF [29,[36][37][38][39]. Moreover, many studies have reported the pivotal role of oxidative stress induced by AF in eliciting programmed cell death or apoptosis through mitochondrial signaling pathways [25,[40][41][42]. ROS induced mitochondrial damage is known to cause uncoupling of mitochondrial oxidative phosphorylation and the associated reduction in mitochondrial membrane potential following AFB1 administration in vivo and in vitro [25,33,35].…”

“…A likely explanation of this association is not yet identified, though consumption of AF-contaminated foods and feeds were reported to cause diverse degrees of liver injury comprising development of fatty cysts, fibrosis, and cirrhosis among humans and animals [23][24][25][26][27]. However, several lines of evidence support oxidative stress as a key factor in AF induced initiation and progression of liver cirrhosis [28][29][30][31].…”

“…Moreover, many studies have reported the pivotal role of oxidative stress induced by AF in eliciting programmed cell death or apoptosis through mitochondrial signaling pathways [25,[40][41][42]. ROS induced mitochondrial damage is known to cause uncoupling of mitochondrial oxidative phosphorylation and the associated reduction in mitochondrial membrane potential following AFB1 administration in vivo and in vitro [25,33,35]. Consequently, mitochondrial alterations cause activation of cytochrome C that modulates Bcl2/Bax gene expression and activate caspase 9 and caspase 3, which results in cell death [41].…”

Proanthocyanidins Alleviates AflatoxinB1-Induced Oxidative Stress and Apoptosis through Mitochondrial Pathway in the Bursa of Fabricius of Broilers

“…Similar results were noted in previous studies. Researchers reported that AFB 1 exposure could result in apoptosis in the liver [45], BF [14], spleen [15], and thymus [46] of broilers, the mechanism associated with the mitochondrial pathway. However, the inclusion of PCs into AFB 1 contaminated diet prevented AFB 1 -induced up-regulation in Bax , caspase-3 , caspase-9 , p53 , and cytochrome-C and down-regulation in Bcl-2 mRNA expression levels as compared to the AFB 1 treated group.…”

Curcumin in antidepressant treatments: An overview of potential mechanisms, pre‐clinical/clinical trials and ongoing challenges

“…108 Besides, curcumin can also ameliorate the aflatoxin B-induced apoptosis through the mitochondrial pathway in liver cells. 109 Furthermore, curcumin can not only mediate neuroprotection against mitochondrial complex I and II inhibitors by activating the nuclear factor erythroid 2-related factor 2 (Nrf2), but also mitigate the mitochondrial dysfunction by suppressing the ROS burst and the enhancing mitochondrial antioxidant gene expression. 110,111 In this regard, the mitochondrial function plays an imperative role in relieving depression related to curcumin treatment.…”