Background: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative
phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development
of nucleoside reverse transcriptase inhibitors (NRTIs)-induced mitochondrial toxicities.
Available options in managing these complications have, so far, produced controversial results, thus
necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging
effects of naringin, a plant-derived flavonoid, have previously been demonstrated.
Objective: This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial
Methods: Wistar rats were randomly divided into Zidovudine (AZT)-only (100 mg/kg body weight
BW); AZT+Naringin (100+50 mg/kg BW); AZT+Vitamin E (100+100 mg/kg BW); Stavudine (d4T)-
only (50 mg/kg BW); d4T+Naringin (50+50 mg/kg BW); d4T+Vitamin E (50+100 mg/kg BW) and
Vehicle (3.0 mL/kg BW)-treated groups, respectively. After 56 days of oral daily dosing, rats were
euthanized by halothane overdose, blood collected by cardiac puncture and livers promptly excised
for further biochemical and ultrastructural analyses.
Results: AZT- or d4T-only caused significant mitochondrial dysfunction and mitochondrial ultrastructural
damage compared to controls, while either naringin or vitamin E reversed indices of mitochondrial
dysfunction evidenced by significantly reduced mitochondrial malondialdehyde (MDA) and
blood lactate concentrations, increased liver manganese superoxide dismutase (MnSOD) activity and
upregulate expression of mitochondrial-encoded subunit of electron transport chain (ETC) complex
IV protein compared to AZT- or d4T-only treated rats. Furthermore, naringin or vitamin E, respectively,
ameliorated mitochondrial damage observed in AZT- or d4T-only treated rats.
Conclusion: Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and
might, therefore, be beneficial in managing toxicities and complications arising from NRTI use.