Switchable hepatic organelles aberrations in DEN-induced mice under the influence of chemically characterized silk sericin

Abstract

Objective: Assessing the beneficial effects of silk sericin against hepatic injury induced by diethylnitrosamine (DEN).

Methods: Aiming at promoting sericin as a natural product able to counteract the hazards of toxic elements, HPLC profile was conducted on the extracted sericin sample versus the standard one to qualitatively identify it. Following sericin treatment on human HepG2 liver cancer cells, many parameters were analyzed in vitro including cell viability, cell cycle, and cell apoptosis. Hepatic pro-inflammatory cytokines as well as histopathological and ultrastructure changes were evaluated in vivo in the different experimental groups.

Results: Sericin exhibited a dose-dependent cytotoxic effect on HepG2 cells with an IC50 of 14.12 + 0.75 μg/mL. The hepatotoxicity of DEN was manifested in mice by increased pro-inflammatory markers (IL-2, IL-6, and TNF-α), decreased IL-10, liver structure deterioration, and characteristic histopathological and ultrastructure changes. Sericin administration reversed most of the observed alterations inflected by DEN.

Conclusions: Our results substantiate the sericin's powerful apoptotic impact in vitro. In experimental mice, combination treatment using sericin together with melatonin appears to be more potent in mitigating the adverse effects of DEN. However, further investigations are needed to identify the underlying mechanism of action and complement the knowledge about the expected medicinal values of sericin.

Keywords: Liver; Mitochondria; Natural products; Oxidative stress; Toxicity.