Abstract Title:

Alpha lipoic acid priming enhances the hepatoprotective effect of adipose derived stem cells in CCl4 induced hepatic injury in-vitro.

Abstract Source:

Eur J Pharmacol. 2021 Jun 9 ;906:174201. Epub 2021 Jun 9. PMID: 34118221

Abstract Author(s):

Faiza Yaqub, Noreen Latief, Hira Butt, Nadia Naseer, Sheikh Riazuddin

Article Affiliation:

Faiza Yaqub


Mesenchymal stem cells are known to support hepatic defense against liver fibrosis. However, the fibrosis induced oxidative microenvironment affects the proliferative, regenerative, and angiogenic properties of mesenchymal stem cells. Alpha lipoic acid (ALA) is a strong anti-oxidant which has been shown to ameliorate the adverse effects of fibrosis that otherwise can lead to severe liver problems like cirrhosis and liver failure. Here, we studied the protective role of ALA primed adipose derived stem cells (ADSCs) against carbon tetrachloride (CClinduced hepatotoxicity in primary hepatocytes in-vitro. Priming of ADSCs helped to abrogate the damaging effects of fibrosis induced oxidative stress as evidenced by significantly reduced levels of alkaline phosphatase (ALP), Alanine Aminotransferase (ALAT) along with decreased lactate dehydrogenase (LDH) release and improved superoxide dismutase (SOD) activity. ALA and ADSCs synergistically down-regulated the expression of Bax gene, an apoptosis regulator while enhancing cell proliferation by up-regulating the expression of Bcl2l1 gene. This treatment improved the expression of albumin (Alb), cytokeratin-8 (Ck8), and hepatic nuclear factor alpha (Hnf4α). Cytochrome P450 2E1 (Cyp2e1) and Alpha fetoprotein (Afp) were down-regulated to lessen the damage caused by CCltreatment. Furthermore, paracrine release of several growth factors like hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and insulin growth factor (IGF) reinforced the improved response of primary hepatocytes against CClinduced hepatotoxicity in the presence of ALA primed ADSCs. This study suggests that ALA priming may improve the therapeutic potential of ADSCs against chronic liver problems by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant factors heme oxygenase 1 (HO-1) and quinone acceptor oxidoreductase-1 (NQO1).

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