Evaluation of the Reproductive Toxicity of L‐Histidine Methyl Ester Hydrochloride of Amphotericin‐B In Vivo

Abstract

Systemic mycosis has increased in recent years. The drug that is used for the treatment of these mycoses is amphotericin‐B, which is a highly toxic drug generating hepatotoxicity and nephrotoxicity. These adverse effects are very serious, which causes an abandonment of the treatment, there are some alternatives such as new lipid formulations of amphotericin‐B. Unfortunately these types of medications are not available for all people because of their high cost. Recently this group has found that derivative AmB (A21) has similar pharmacological effects of AmB but not induce nephotoxicity and hepatotoxicity. However we unknown if it induces other side effects than AmB. Therefore, the aim of this work was to evaluate the effect of a derivative of AmB (A21) on the structure and function of the male and female reproductive system of Wistar ratsDerivative A21 was given intraperitoneally at a dose of 2 mg/Kg daily to female and male rats for a period of 45 days, 120 days and a third group received during 120 days and 65 days without treatment with the analog A21 in order to study the reversion of the injury.. Samples were collected after sacrificed and tissues were fixed with formalin 4% then were cut to histology which were stained with hematoxylin‐eosin. Blood was obtained by cardiac puncture and seric hormone levels were measured. Testosterone levels for male rats and progesterone for female rats, levels were measured by an Enzyme‐linked Immunosorbent Assay (ELISA).The analog A21 did not cause structural and functional damage in male and female reproductive system from rats when were treated for a period of 45 days, since the morphology was integrated and hormone levels were normal compared with their respective control. The analog A21 caused structural and functional damage when was given during 120 days. Testosterone levels was increased (3‐fold) and were observed several alterations in the structure of testis. While in female rats in this period of treatment did not generate structural and functional damage. When rats were treated during 120 days, suspended the treatment and sacrificed 65 days without treatment, the structures of the male reproductive system was reestablished and the levels of testosterone reduced. Female Wistar rats dis not show any functional and structural damage.Derivative A21 is able to induce structural and functional damage in male reproductive system after 120 days of treatment, however, this effect is reverted after 65 days after stopping the treatment. Derivative did not show any alteration in female reproductive system. Therefore, derivative could be used as treatment for mycosis with the advantage that the side effects produced are reversible.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.