Delta-9-tetrahydrocannabinol ameliorates oxidative stress, mitochondrial redox state, and neuroinflammation induced by high-fructose diet

Abstract

This study investigates the effects of a high-fructose diet (HFD) on brain oxidative stress, mitochondrial redox state, and pro-inflammatory cytokine expression, and specifically evaluates whether delta-9-tetrahydrocannabinol (THC) attenuates these HFD-induced changes. Thirty-two Sprague–Dawley rats were divided into four groups: Control, HFD (10% fructose in drinking water for 12 weeks), THC (1.5 mg/kg daily for the last 4 weeks), and HFD + THC (HFD for 12 weeks with THC co-administration during the final 4 weeks). Biochemical biomarkers (AOPP, DT, KYN, MDA, AGE, T-SH, NADH, FAD, serotonin, insulin) and mRNA expression levels of inflammation-related genes (IL-6, IL-1β, TNF-α, NF-κB) were analyzed in brain tissues. The HFD significantly increased levels of protein oxidation (AOPP, DT, KYN, AGE); lipid peroxidation (MDA); and NADH and FAD fluorescence whilst decreasing total thiol (T-SH) content. HFD also increased the mRNA expression of all inflammatory markers examined. In contrast, THC treatment significantly reduced oxidative damage and NADH and FAD fluorescence and reduced the relative mRNA expression of the investigated inflammation-related genes. Strong positive correlations were observed between pro-inflammatory cytokine mRNA expression and oxidative stress markers. HFD causes significant biochemical and molecular damage to the brain. THC administration was associated with a significant attenuation of HFD-induced oxidative stress, mitochondrial redox state, and pro-inflammatory cytokine expression, suggesting that it may mitigate diet-associated neurochemical perturbations.