title: Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity.
abstract: 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.
  
  
  
  This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial toxicity.
  
  
  
  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. &lt;/p&gt; 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.
  
  
  
  Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and might, therefore, be beneficial in managing toxicities and complications arising from NRTI use.
authors.affiliation: Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville campus, Durban 4001, South Africa. fadebiyi@gmail.com.
authors.forename: Adebiyi
authors.initials: A
authors.lastname: Oluwafeyisetan
authors.forename: Adebiyi
authors.initials: A
authors.lastname: Olubunmi
authors.forename: Owira
authors.initials: O
authors.lastname: Peter
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D044950:Flavanones / Q000008:administration & dosage*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009705:Nucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D044950:Flavanones; D016166:Free Radical Scavengers; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; C005274:naringin