ABSTRACT
Background: Lopinavir/ritonavir (LPV/r) could be associated with adverse cardiac event. Antiretroviral drugs containing LPV/r are used concurrently with sulfamethoxazole/trimethoprim (SMX/TMP) which may also be associated with adverse cardiac events in the management of human immunodeficiency virus and co-infection. The concurrent use of these drugs may precipitate synergistic adverse cardiac events. This work, therefore, evaluates the possible toxicological interaction of co administered LPV/r and SMX/TMP on cardiac function and architecture of albino rats. Methods: Seventy five (75) animals which were divided into five groups (A-E) of fifteen (15) animals each were used in this study. Animals in Group A, which served as the control, were treated with 1% ethanol orally. Animals in Group (B-E) were treated with oral doses of SMX/TMP (11.2/2.3 mg/kg), LPV/r (11.4/2.9 mg/kg), and combine doses of SMX/TMP+LPV/r for 2-8 weeks, respectively. Blood sample was collected and evaluated for pack cell volume, hemoglobin, red blood cell and white blood cell. Cardiac tissues were evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSHPX), and histopathological changes. Results: Treatment with SMX/TMP LPV/r and their combine doses produced no significant effect on cardiac weight. SMX/TMP significantly decreased red blood cell and hemoglobin while LPV/r produced no significant hematologic effect. Combine doses of these agents produced no synergistic hematologic effects. Treatment with a single and combine doses of these agents produced time-dependent decrease in SOD, GSHPX and increase in MDA, but no synergistic effects were produced by their combine doses. Normal cardiac myocytes with patchy collection of mononuclear inflammatory cells infiltration of the interstitium were observed after treatment with single and combined doses of these agents but without any synergistic effect when agents were co-administered. Conclusion: In this study, the co-administration of SMX/TMP and LPV/r did not produce any significant synergistic effects on all the evaluated parameters; hence, the concurrent use of these agents in the management of HIV and co-infections may be safe on cardiac function and structure.
ABSTRACT
Background: Human immunodeficiency virus/acquired immune deficiency syndrome is usually associated with co-infections which has allow the concurrent use of sulfamethoxazole/trimethoprim (SMX/TMP)+Lopinavir/ritonavir (LPV/r). The concurrent use of these drugs may have possible adverse effects on the kidney because they are individually associated with adverse renal events. This study, therefore evaluates the possible effect of co-administered SMX/TMP+LPV/r on kidney function and architecture of albino rats. Methods: Seventy five (75) animals which were divided into five groups were used in this study. Group A, which served as control, contained 15 animals which were treated with 1% ethanol orally. Group B-E, which contained 15 animals each, was further subdivided into three groups of five animals each. Animals in these groups were treated with oral doses of SMX/TMP (11.2/2.3 mg/kg), LPV/r (11.4/2.9 mg/kg), and combined doses of SMX/TMP+LPV/r for 2-8 weeks respectively. Serum levels of creatinine, urea, and uric acid were evaluated. Kidney tissue was evaluated for malondialdehyde (MDA), superoxide dismutase (SOD), and histopathological changes. Results: Treatment with single doses of SMX/TMP, and LPV/r, produced a time-dependent increase in serum creatinine and urea. But no significant synergistic effects on serum creatinine and urea were observed when these agents were co-administered. Treatment with single and combine doses of these agents had no significant effects on serum uric acid level. Treatment with single agents produced time-dependent increase in kidney MDA and decrease in SOD level but without any significant effects when these agents were co-administered. Kidney of animals treated with single doses of these agents showed hypercellarity of the interstitium of the glomeruli and vascular congestion with no synergistic effects when these agents were co-administered. Conclusion: Concurrent use of SMX/TMP+LPV/r in the management of HIV and co-infection may not have any deleterious effect on the renal system.