Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice

SIMPLE SUMMARY: In any animal species, involuntary exposure to unknown agents may increase genetic material damage. This genetic damage can also induce the appearance of diseases such as cancer or other pathologies, including problems that can be passed on to the offspring of the damaged individual. For instance, living organisms may be affected due to the use of medications or exposure to certain chemical, physical, or biological agents which cause cell failure. This impaired function acts as an indicator that helps identify and evaluate damage in order to avoid or minimize it. In this work, excessive doses of a cosmetic drug for topical use in dermatological treatments, known as minoxidil, produced defects in the blood of hairless mice, particularly in red cells, indicating loss of DNA, a situation that may compromise life or the offspring by causing damage to their genetic material. It is important to consider that compounds may be tissue- or species-specific, although we cannot rule out the possibility that similar damage could occur in other animal species. Thus, excessive exposure to this compound should be prevented. ABSTRACT: SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.