Red Palm Oil Ameliorates Oxidative Challenge and Inflammatory Responses Associated with Lipopolysaccharide-Induced Hepatic Injury by Modulating NF-κβ and Nrf2/GCL/HO-1 Signaling Pathways in Rats

Olawale R Ajuwon; Jeanine L Marnewick; Oluwafemi O Oguntibeju; Lester M Davids

doi:10.3390/antiox11081629

Red Palm Oil Ameliorates Oxidative Challenge and Inflammatory Responses Associated with Lipopolysaccharide-Induced Hepatic Injury by Modulating NF-κβ and Nrf2/GCL/HO-1 Signaling Pathways in Rats

Antioxidants (Basel). 2022 Aug 22;11(8):1629. doi: 10.3390/antiox11081629.

Authors

Olawale R Ajuwon¹, Jeanine L Marnewick², Oluwafemi O Oguntibeju³, Lester M Davids⁴

Affiliations

¹ Redox Biology Research Laboratory, Department of Biochemistry, Federal University Oye-Ekiti, Oye-Are Road, P.M.B. 373, Oye-Ekiti 371104, Nigeria.
² Applied Microbial and Health Biotechnology Institute, Cape Peninsula University of Technology, Bellville 7535, South Africa.
³ Phytomedicine and Phytochemistry Group, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville 7535, South Africa.
⁴ Graduate School of Business, University of Cape Town, Cape Town 7700, South Africa.

Abstract

Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant and anti-inflammatory effects. In this study, we assess the protective effect and mechanistic action of RPO using a lipopolysaccharide (LPS)-induced hepatic injury model. Male Wistar rats were assigned into four groups (10 animals/group): normal control (NC), RPO, LPS and RPO + LPS. Animals in the RPO and RPO + LPS groups were administered RPO (200 μL/day) for 28 days. On the 27th day of experiment, animals in LPS and RPO + LPS groups were injected with LPS (0.5 mg/kg body weight). Animals were sacrificed 24 h later, and blood and liver tissues harvested for biochemical and molecular analysis. RPO resolved hepatic histological dysfunction induced by LPS, and lowered alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transferase activities in the serum. Hepatic malondialdehyde and conjugated dienes, as well as pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6 and TNFα were significantly diminished (p < 0.05) by RPO pre-treatment. Activity of hepatic antioxidant enzymes including superoxide dismutase, glutathione reductase, glutathione peroxidase, as well as glutathione redox status (GSH:GSSG), and markers of antioxidant capacity that decreased as a result of LPS injection were improved by RPO pre-treatment. Mechanistically, RPO up-regulated mRNA expression of redox sensitive transcription factor Nrf2 and its downstream targets GCL and HO-1, while also suppressing the expression of NFκβ and associated inflammatory protein, Iκβ kinase (IκKβ). In conclusion, this study highlights the ameliorating effects of RPO against LPS-induced hepatic injury and revealed the Nrf2/GCL/HO-1 and NFκβ signaling axis as potential contributing mechanisms.

Keywords: antioxidant; inflammation; lipopolysaccharide; oxidative stress; red palm oil.

Grants and funding

This research was funded by Cape Peninsula University of Technology, South Africa. The APC was funded by Cape Peninsula University of Technology, South Africa. O.R.A. received a Postdoctoral Fellowship from the Claude Leon Foundation, South Africa, at some point during the course of this study.