Abstract
Introduction: Lopinavir/ritonavir (LPV/r) may cause renal dysfunction such as electrolyte and acid base disorders and alteration in kidney morphology. Drug–induced renal dysfunction can occur through multiple mechanisms including oxidative stress and inflammation. Objectives: The current study aimed at evaluating the protective effects of melatonin (MT) and alpha lipoic acid (ALA) against serum electrolytes and kidney histology of LPV/r-treated rats. Adult albino rats were randomized into six groups (A to F). Rats in the control groups were treated orally with normal saline and 1% ethanol as placebo and solvent control for 90 days respectively. Rats in the experimental groups were pre-treated orally with 10 mg/kg of MT, 10 mg/kg of ALA, and MT+ ALA daily before treatment with 22.9/5.71, 45.6/11.4 94 and 91.4/22.9 mg/kg/d of LPV/r for 90 days respectively. Materials and Methods: At the end of treatment, rats were euthanized. Blood samples were collected and serum samples were extracted and evaluated for electrolytes, total protein, and albumin. Additionally, kidneys were excised via dissection and evaluated for morphological changes. Results: Significant (P<0.001) decreases in serum sodium, potassium, chloride, bicarbonate, total protein and albumin in a dose-dependent fashion were obtained in LPV/r-treated rats when compared to control. Dose-dependent kidney morphological changes characterised by tubular necroses were obtained in LPV/r-treated rats. The observations in LPV/r-treated rats were significantly reversed in MT (P<0.01), ALA (P<0.01) and MT+ALA (P<0.001) pre-treated rats when compared to LPV/r-treated rats. Conclusion: MT and ALA can serve as adjuvant therapies for LPV/r-associated alterations in serum electrolytes and kidney histology.
Highlights
Lopinavir/ritonavir (LPV/r) may cause renal dysfunction such as electrolyte and acid base disorders and alteration in kidney morphology
Implication for health policy/practice/research/medical education: This study discovered that melatonin and alpha lipoic acid may have clinical applications as adjunct therapies for lopinavir/ritonavir associated alterations in serum electrolytes and kidney morphology
Serum Na+, K+, Cl- and HCO3- levels were normal (P > 0.05) in rats treated with MT, alpha lipoic acid (ALA) and MT+ALA when compared to control (Table 1).On the other hand, serum Na+, K+, Cl- and HCO3- were significantly (P < 0.001) decreased in a dose-dependent fashion in rats treated with LPV/r when compared to control (Tables 2 and 3)
Summary
Lopinavir/ritonavir (LPV/r) may cause renal dysfunction such as electrolyte and acid base disorders and alteration in kidney morphology. Rats in the experimental groups were pre-treated orally with 10 mg/kg of MT, 10 mg/kg of ALA, and MT+ ALA daily before treatment with 22.9/5.71, 45.6/11.4 94 and 91.4/22.9 mg/kg/d of LPV/r for 90 days respectively. The use of lopinavir/ritonavir (LPV/r) as an essential component of highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected people. It has reduced the risk of early death from opportunistic infections and other consequences that could arise as a result of HIV infection. Oxidative stress through free radical production leading to lipid, DNA, and protein damage with the activation of apoptotic pathways, and the initiation of inflammatory response has been implicated in drug- induced kidney injury [5]
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