Coenzyme Q10 may protect ovarian tissue against by the nearly century-old drug methotrexate caused gonadotoxicity: a biochemical, flow cytometric, and histopathological study

Abstract

Methotrexate (MTX) is still a broad-spectrum drug that has been used for almost a century for leukemia, rheumatoid arthritis, ectopic pregnancy. This study investigates the protective effects of coenzyme Q10 (CoQ10) on MTX induced gonadotoxicity. Twenty-four female wistar albino rats were divided into four groups. Control group; 1 ml corn oil was applied by oral gavage (p.o.). CoQ10 group; 100 mg/kg CoQ10 (in 1 ml corn oil) was applied by p.o. for seven days. MTX group; 20 mg/kg MTX intraperitoneal (i.p.) was used one time on the first day of the experiment. MTX + CoQ10 group; 20 mg/kg MTX i.p. one time and 100 mg/kg CoQ10 (in 1 ml corn oil) was applied p.o. for seven days. At the end of the experiment, all animals were euthanized under anesthesia, and blood samples were taken from intracardiac. The both sides ovaries were taken out and were put in to neutral formalin. Biochemical analysis for serum anti-mullerian hormone (AMH), flow cytometry for apoptosis (Annexin V), and histopathologic analysis with follicle counting were performed in ovarian tissues. According to results of follicle counting, apoptosis, morphometric and AMH analysis; there was no statistically significant difference in terms of follicle numbers and ovarium diameter between all groups. However, apoptosis significantly increased in the MTX group and decreased in the MTX + CoQ10 group. AMH level was decreased in the MTX group and interestingly significantly increased in the only CoQ10 treatment group and. As a result, CoQ10 has protective effects in terms of apoptosis and AMH against MTX induced gonadotoxicity.