Biphasic Dose-Response Effects of n-Hexane Extract of Macadamia integrifolia Nuts on Oxidative Stress and Inflammatory Markers in Male Wistar Rats

Abstract

Aims: To investigate the dose-dependent effects of n-hexane extract of Macadamia integrifolia nuts on oxidative stress biomarkers and inflammatory cytokines in male Wistar rats. Study design: This study employed an experimental, controlled, dose–response animal study. Place and duration of Study: The study was conducted in an animal house of the Department of Human Physiology, Rivers State University, Nigeria over a period of 28 days Methodology: Twenty-four Male Wistar r (n=24) were randomly allocated into four groups (n=6 per group): control (vehicle only), low dose (250 mg/kg), moderate dose (500 mg/kg), and high dose (1000 mg/kg) of n-hexane extract of M. integrifolia nuts. Following the experimental period, serum levels of glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured as oxidative stress markers. Inflammatory markers including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and C-reactive protein (CRP) were also quantified. Results: The n-hexane extract demonstrated a biphasic dose–response pattern was observed. The low dose significantly reduced antioxidant enzyme activities, increased lipid peroxidation, and elevated pro-inflammatory cytokines compared to control (p < 0.05), indicating oxidative and inflammatory stress. The moderate dose restored biomarkers to near-control levels, suggesting physiological homeostasis. Notably, the high dose significantly enhanced antioxidant defenses beyond baseline and suppressed inflammatory mediators below control values (p < 0.05), demonstrating potent antioxidative and anti-inflammatory effects. Derived indices corroborated these findings, highlighting dose-dependent shifts in redox balance and systemic inflammatory burden. Conclusions: These findings demonstrate a characteristic hormetic biphasic dose-response of n-hexane extract of M. integrifolia nuts, whereby low doses induce oxidative stress and inflammation, moderate doses maintain homeostasis, and high doses confer significant antioxidant and anti-inflammatory benefits. These results provide important insights for the therapeutic application of macadamia nut lipophilic constituents.