Journal of Nutritional Biochemistry
Journal of Nutritional Biochemistry
4 years ago

Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation

Grape seed procyanidin extract ameliorates lead-induced liver injury via miRNA153 and AKT/GSK-3β/Fyn-mediated Nrf2 activation
Lead-induce hepatotoxicity is characterized by an extensive oxidative stress. Grape seed procyanidin extract (GSPE) possesses abundant biological activities. Herein, we investigated the protective role of GSPE against lead-induced liver injury and determined the potential molecular mechanisms. In vivo, rats were treated with/without lead acetate (PbAc) (0.05%, w/v) in the presence/absence of GSPE (200 mg/kg). In vitro, hepatocytes were pretreated with/without GSPE (100 μg/mL) in the presence/absence of PbAc (100 μM). PbAc administration to rats resulted in anemia, liver dysfunction, lead accumulation in the bone and liver, oxidative stress, DNA damage, and apoptosis. GSPE significantly attenuated these adverse effects, except lead accumulation in liver. GSPE also decreased the expression of miRNA153, increased the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and levels of its downstream protein, and protein kinase B (AKT) phosphorylation in PbAc-induced liver injury. In primary hepatocytes treated with PbAc, GSPE increased hepatocyte viability, and decreased lactate dehydrogenase release and reactive oxygen species levels. Dietary GSPE attenuated PbAc-induced liver injury in rats via an integrated mechanism associated with the miRNA153 and AKT/glycogen synthase kinase 3 beta/Fyn-mediated Nrf2 activation.

Publisher URL: www.sciencedirect.com/science

DOI: S0955286317305053

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