Low-dose quercetin at 25 mg/kg ameliorates dolutegravir-lamivudinetenofovirdisoproxilfumarate-inducedcardiohepato-renal toxicities in Wistar rats

Abstract

Combination antiretroviral therapies (cARTs) are linked with multiple-organ system (MOS) toxicities in laboratory animals, and in humans undertaking treatment for HIV/AIDS. The ameliorative potential of low-dose quercetin following cART-associated MOS-toxicities in cardio-hepato-renal organs was evaluated in in vivo model. Oral administration of cART (Dolutegravir 50 mg, Lamivudine 300 mg and Tenofovir disoproxil fumarate 300 mg [DLT]) at 9.29 mg/kg, was challenged against low-dose quercetin 25 mg/kg body weight (bw) in Wistar rats. Group 1, the normal control (NC) received distilled water (5 mL), while groups 2 to 4 received quercetin (25 mg), DLT (9.29 mg), and DLT+quercetin (9.29 mg+25 mg respectively), per kg bw. All administrations lasted for 14 days, and thereafter animals were humanely sacrificed after intraperitoneal anesthesia injection with 100 mg ketamine /5 mg xylazine per kg bw followed by cervical dislocation. Blood and organs were harvested for analyses using standard protocols. The serum concentrations of lipid parameters [total cholesterol, triglycerides, LDL-cholesterol, and VLDL-cholesterol], liver biomarkers (total-bilirubin, direct-bilirubin, and transaminases], and kidney biomarkers [urea and creatinine] were significantly increased (p<0.05) while electrolytes (Na+, K+, Cl− and HCO3 −) were significantly decreased (p<0.05) in DLT group but improved in DLT+Q group. Histopathology demonstrated distorted myocytes, hepatocytes and renal tubules, fatty liver with vacuolization, dystrophied glomeruli and distorted renal interstitium in DLT group, compared with normal appearing histoarchitectural features in NC and DLT+Q groups. In conclusion, oral administration of low-dose quercetin (25 mg/kg) ameliorated cART-associated cardio-hepato-renal toxicities in rats, improving their biomarkers and histoarchitecture