Effect of co-administered lopinavir/ritonavir and sulfamethoxazole/trimethoprim on cardiac function and architecture of albino rats

Adikwu Elias, Deo Oputiri, Zidafamor Jimmy, Obele Rejoice, Asalagha Marian, Oru-Bo Precious Geoffrey, Anthony Timothy Gilbert

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.


Keywords


Cardiac, Lopinavir/Ritonavir, Rats, Sulfamethoxazole/Trimethoprim, Toxicity

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