Sub-chronic drug toxicity investigation of highly active anti-retroviral therapy (HAART) in Wistar rats

Iheonunekwu, Goodness Chigozirim and Alisi, Chinwe Sylvanus and Onuoha, Chinyere Henrietta (2025) Sub-chronic drug toxicity investigation of highly active anti-retroviral therapy (HAART) in Wistar rats. GSC Biological and Pharmaceutical Sciences, 30 (3). pp. 218-232. ISSN 2581-3250

The widespread use of highly active antiretroviral therapies (HAART) for HIV/AIDS treatment has significantly improved patient outcomes. However, long-term administration of these therapies can have unintended consequences. This study investigated the potential adverse effects of LZN, a combination antiretroviral drug, on hematological parameters and serum biomarkers in wistar rats. A total of forty-eight (48) female Wistar rats were divided into four groups: a control group and three groups administered LZN orally at doses of 25, 50, and 100 mg/kg for 90 days. Hematological parameters and serum biomarkers were assessed at 30, 60, and 90 days. Result obtained in this study revealed that the LD50 of the LZN drug sample was calculated to be 2154.07mg/kg body weight in rat model which is an indication that the drug sample is of low toxicity or is relatively safe with moderate safe margin. The haematological result showed that prolonged administration of LZN had an adverse effect on the Hb, PCV, RBC, TWBC, platelets count and the MCH indices after 60 days of administration, with a resultant microcytic hypochromic form of anaemia and classic neutropenia (dose and time dependently). The significant increases in the serum levels of ALT, AST, ALP, creatinine and urea (the liver and kidney biomarkers) in the rats administered the graded doses of the LZN drug sample at prolonged administration, suggested hepatocellular damage and nephrotoxicity, with significant alteration of electrolytes metabolism of sodium, chloride, potassium and bicarbonate concentrations (disturbance in acid-base balance). Also, the abnormal milieu of GSH and MDA serum levels evidently indicate an increased oxidative stress and lipid peroxidation caused by prolonged administration. LZN, while effective for HIV/AIDS treatment, can have long-term adverse effects on hematological parameters, organ function, and electrolyte balance. These findings emphasize the importance of regular monitoring and potential adjustments in therapy to mitigate these risks. Further research is needed to fully understand LZN's impact and inform optimal treatment strategies.