Molecular Mechanism and Pathogenesis-Oriented Treatment of Antipsychotic Drug-Induced Infertility in Female Rats

Abstract

Typical and atypical antipsychotics may cause subfertility through oxidative stress in reproductive cells and endocrine axis. This experimental study was designed to determine the effects of adenosine triphosphate (ATP) treatment on oxidative stress markers and hyperprolactinemia in subfertility due to antipsychotics. A total of 54 Albino Wistar female rats were divided into nine groups as the healthy (HG), haloperidol (HPL), olanzapine (OLZ), clozapine (CLZ), aripiprazole (ARZ), ATP+haloperidol (ATP+HPL), ATP+olanzapine(ATP+OLZ), ATP+clozapine (ATP+CLZ) and ATP+aripiprazole (ATP+ARZ) groups. ATP was injected intraperitoneally (ip) at a dose of 25 mg/kg to animals in ATP+HPL, ATP+OLZ, ATP+CLZ, and ATP+ARZ groups. HG, HPL, OLZ, CLZ, and ARZ groups were given the same volume of distilled water via ip. One hour after administration of drugs and solvent, haloperidol (2 mg/kg) for ATP+HPL and HPL groups, olanzapine (2 mg/kg) for ATP+OLZ and OLZ groups, clozapine (20 mg/kg) for ATP+CLZ and CLZ groups and aripiprazole (3 mg/kg) for ATP+ARZ and ARZ groups was given orally to by gavage. This procedure was repeated once a day for 15 days. After this period, blood samples were taken for oxidant, antioxidant and prolactin measurement and the animals were kept with mature male rats for one month for breeding. The degree of oxidative stress, hyperprolactinemia and subfertility caused by antipsychotics were found to be haloperidol, olanzapine, clozapine, aripiprazole, in order of frequency. ATP administration reversed the increase in oxidants markers and the decrease of antioxidants significantly. ATP administration prevents subfertility due to antipsychotic drugs.