Nrf2 protein as a therapeutic target during diethylnitrosamine-induced liver injury ameliorated by β-carotene-reduced graphene oxide (βC-rGO) nanocomposite

Abstract Oxidative stress plays a central role in the incidence of liver injury. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a key protein regulator of antioxidant response elements (ARE)-mediated gene expression. Thus, Nrf2 can be regarded as a plausible therapeutic target during liver injury. β-Carotene is implicated as one of the important antioxidant with diverse health benefits. The delivery of β-carotene to the target tissue has been debatable due to its low bioavailability, poor water solubility and instability. Here, a nanocomposite of β-carotene with reduced graphene oxide (βC-rGO) has been developed to demonstrate its pronounced effect in regulating Nrf2 to trigger protection against diethylnitrosamine (DEN)-induced hepatic fibrosis in rats. The rGO and βC-rGO samples were characterised by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Progress of disease was monitored through ultrasonography, in vitro liver and serum biochemistry (alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, lipid peroxidation, protein carbonyls, superoxide dismutase, catalase, glutathione-S-transferase, Nrf2, vitamin-A, retinol dehydrogenase), histopathology, confocal and ultrastructural studies. In fibrotic animals liver biochemistry was significantly altered along with massive changes in liver anatomy. βC-rGO ameliorates experimental fibrogenesis and restores liver functioning due to increased availability of β-carotene in the liver. It is suggested that βC-rGO nanocomposite promotes cellular antioxidant status via upregulation of Nrf2 protein factor and invigorate hepatic stellate cells (HSCs) through restoring vitamin-A.