In vivo cytogenotoxicity testing of isotretinoin by the micronucleus assay in the blood of male Sprague-Dawley rats Isotretinoin is cytotoxic and genotoxic

Abstract

Isotretinoin (ISO), one of vitamin A-derived retinoids, is comparatively the most widely prescribed drug in acne vulgaris pathogenesis. Despite its excellent therapeutic success, the systemic use of this drug showed undesirable serious side effects such as teratogenesis, oxidative stress, and genotoxicity. The uses of retinoids in cancer therapy are limited due to severe adverse reactions. This has led the scientific community to ask for further studies qualifying ISO features and comparing their efficacy and safety. The purpose of this study was to evaluate the cytogenotoxicity of multiple oral doses (5, 10, 15, and 20 mg/kg, daily for seven consecutive days) of ISO in male Sprague-Dawley rats. The micronucleus assay was used to investigate genotoxicity biomarkers such as the percentage of micronucleated polychromatic erythrocytes (%MNPCEs) and the percentage of aberrant cells (%Abc). Another goal was to test the cytotoxicity of the drug by measuring the ratio between PCEs and normochromatic erythrocytes (NCEs) (PCEs/NCEs). In comparison with the control, the three cytogenetic endpoints: %MNPCEs, P/N, and %Abc significantly (P ≤ 0.0017) dose-dependent increase. This suggested genotoxicity and cytotoxicity of the tested ISO doses. Therefore, the therapeutic uses of ISO should be restricted to a very narrow range border. Further studies are needed to shed more light on the safety profile of ISO therapy.

Morphological, histopathological, and immunohistochemical changes in tissues of adult male Sprague-Dawley rats orally treated with isotretinoin

“…Also, ISO was cytogenotoxic. 29 Cytotoxicity is one of the primary mechanisms that may cause acute or chronic damage. 5 Cytotoxicity may be followed by cell death, apoptosis, or necrosis, 29 leading to a drop in germinal epithelial cells.…”

“…29 Cytotoxicity is one of the primary mechanisms that may cause acute or chronic damage. 5 Cytotoxicity may be followed by cell death, apoptosis, or necrosis, 29 leading to a drop in germinal epithelial cells. The results gained for the percentages of sperm aberrations 28 permit establishing a connection between the seminiferous epithelium changes and the decrease in the epididymal weight.…”