Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications.

Oluwafeyisetan Adebiyi,Olubunmi Adebiyi,Peter Owira

doi:10.3390/nu7125540

Oluwafeyisetan Adebiyi, Olubunmi Adebiyi + Show 1 more

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https://doi.org/10.3390/nu7125540

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Journal: Nutrients	Publication Date: Dec 10, 2015
Citations: 82	License type: CC BY 4.0

Affiliation: University of KwaZulu-Natal

Abstract

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7) were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT) (groups I, II III), 50 mg/kg stavudine (d4T) (groups IV, V, VI) and 3 mL/kg of distilled water (group VII). Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy.

Highlights

The introduction of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infections [1,2,3]
The current guidelines on administration of HAART recommend a combination of two Nucleoside Reverse Transcriptase Inhibitors (NRTIs), one nucleoside reverse transcriptase inhibitors (NNRTIs) or a protease/integrase inhibitor depending on efficacy and the patient’s tolerability [4,5]
Effects of Naringin on Metabolic Complications of NRTIs AZT or d4T administration resulted in significant (p < 0.05) decrease in total body weight, increase in abdominal fat mass and liver index compared to controls (Figures 1 and 2A,B; Table 2)

Summary

Introduction

The introduction of highly active antiretroviral therapy (HAART) has reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infections [1,2,3]. The current guidelines on administration of HAART recommend a combination of two NRTIs, one NNRTIs or a protease/integrase inhibitor depending on efficacy and the patient’s tolerability [4,5]. Zidovudine (AZT) and stavudine (d4T) have historically been included as components of various combinations of NRTIs which serve as backbone of HAART [6]. While antiretroviral agents have reduced the morbidity and mortality associated with HIV infection, there is persistent increase in the prevalence of these metabolic complications which threaten the success obtained so far with HAART treatment

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Conclusion