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Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity
Adebiyi Oluwafeyisetan1, Adebiyi Olubunmi, Owira Peter
1Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville campus, Durban 4001, South Africa. fadebiyi@gmail.com.
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 toxicity.
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. </p> 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.
Insights
Naringin, a plant flavonoid, effectively protected against mitochondrial damage caused by nucleoside reverse transcriptase inhibitors (NRTIs). This antioxidant may help manage NRTI-related toxicities.
Area of Science:
- Mitochondrial toxicology
- Pharmacology
- Biochemistry
Background:
- Nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial toxicity.
- Mechanisms involve reactive oxygen species (ROS) and impaired oxidative phosphorylation (OXPHOS).
- Current management options yield controversial results, necessitating new therapeutic agents.
Purpose of the Study:
- To investigate the protective effects of naringin against NRTI-induced mitochondrial toxicity.
Main Methods:
- Wistar rats were treated with Zidovudine (AZT) or Stavudine (d4T) alone or in combination with naringin or Vitamin E for 56 days.
- Biochemical and ultrastructural analyses of liver tissues and blood were performed.
- Key markers included malondialdehyde (MDA), lactate, manganese superoxide dismutase (MnSOD) activity, and electron transport chain (ETC) complex IV protein expression.
Main Results:
- AZT or d4T induced significant mitochondrial dysfunction and ultrastructural damage.
- Naringin and Vitamin E reversed these effects, reducing MDA and lactate levels.
- Both agents increased MnSOD activity and upregulated ETC complex IV protein expression.
Conclusions:
- Naringin ameliorates oxidative stress and mitochondrial damage induced by NRTIs.
- Naringin shows potential as a beneficial agent for managing NRTI-related toxicities and complications.
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