Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl4-induced hepatotoxicity.

Abstract

Background: Xenobiotic-induced liver injury is a clinically reverent condition which may influence the development of steatohepatitis via affecting numerous pathways such as oxidative stress, inflammation, mitochondorial functioning and fatty acid biosynthesis. The current study was conducted to survey the antioxidant effect of grape seeds extract nanoparticles (GS extract NPs) against CCl₄-induced oxidative stress, hepatic dysfunction and inflammatory changes.

Methods: Hydroethanolic Grape seed (GS) extract was prepared and characterized using high performance liquid chromatography (HPLC), inductively coupled plasma-mass spectrometry (ICP-MS) and gas chromatography-mass spectrometry (GC-MS). Then, GS extract NPs were synthesized and in vitro antioxidant, anticoagulant, cytotoxicity and anti-inflammatory testes confirmed biological activity. Finally, Twenty-five male Sprague-Dawley rats were divided into five groups (n = 5/group). Either GS extract (200 mg/kg/day) or GS extract NPs (100 mg/kg/day) were orally administrated independently to CCL₄-intoxicated (0.5 ml/kg twice a week for 3 weeks) rats. Four weeks after the treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were monitored. In addition, hepatic Malondialdehyde (MDA), Superoxide dismutases (SOD), Glutathione (GSH) and catalase (CAT) and hepatic inflammatory cytokines were assessed.

Results: GS extract NPs were spherical-shaped and regular particles (size: 16.5 to 22.5 nm and zeta potential: -39.42 mv). CCL₄ -intoxicated rats showed increase of serum ALT, AST, ALP, elevation in MDA level accompanied by a decline in SOD, GSH and CAT levels in liver, compared with CCL₄-untreated rats. Immunologically, serum C-Reactive Protein (CRP) and hepatic interleukin 1β (IL-1β), IL-4, IL-6 and Tumor Necrosis Factor-alpha (TNF-α) showed significant elevation, compared with CCL₄ -untreated rats. Conversely, GS extract NPs supplementation potentially ameliorate hepatic functions by normalization of serum ALT, AST and ALP, reduced MDA level, improved antioxidant CAT, regulated liver inflammatory cytokines via maximal reduction of hepatic IL-1β, IL-4, IL-6 and TNF-α.

Conclusion: GS extract NPs augmented the antioxidant and anti-inflammatory properties of GS extract thereby protecting the liver against oxidative stress induced by CCl₄ as hepatic xenobiotic.

Clinical trial number: Not applicable.