In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 133, No. 1 ( 2023-07), p. 82-97
Abstract:
A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother‐to‐child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. Method An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28‐day feeding test was conducted to assess the potential subacute toxicity. Results In mice, the LD 50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose‐dependent manner in mice ( P 〈 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high‐dose group was lower than that in the control group ( P 〈 0.05); the relative weights of the liver, kidney, spleen and brain increased ( P 〈 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high‐dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high‐dose group increased ( P 〈 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high‐dose group were significantly decreased ( P 〈 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium‐ and high‐dose groups increased significantly ( P 〈 0.05). Conclusion The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.
Type of Medium:
Online Resource
ISSN:
1742-7835
,
1742-7843
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2151592-X
SSG:
15,3