الفهرس 
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Abstract
Olanzapine (OLZ) is anatypical antipsychotics which is used in treatment of psychiatric disorders as schizophrenia and bipolar disorder. However, adverse drug reaction (ADRs) may appear with it′s use. Antipsychotic use may affect reproductive system causing sexual dysfunction which is a common problem among the general population as well as among those suffering from psychiatric disorders and/or receiving psychotropic Drugs. To minimize or prevent theses ADRs, vitamin E which is an effective antioxidant agent, has been suggested.
The current investigation is an experimental study designed to evaluate the possible toxic effect of olanzapine on reproductive system and the possible protective effect of Vitamin E (Vit E) in male albino rats.
Seventy adult male albino rats weighing (230-260gm) and (3.5- 4 months in age) were randomly assigned into seven groups, each group contains 10 rats. Group1 (control untreated group) received distilled water, orally for 8 weeks. Group2 (rats received OLZ in a dose of 2.5 mg/kg), Group3 (rats received OLZ 5 mg/kg) and Group4 (rats received OLZ 10 mg/kg), Group5 (rats received OLZ in a dose of 2.5 mg/kg OLZ with Vit E in a dose of 200 mg/kg/d, Group6 (rats received OLZ 5 mg/kg with Vit E in a dose of 200 mg/kg/d) and Group7 (rats received OLZ 10 mg/kg with Vit E in a dose of 200 mg/kg/d).All administered drugs were given orally daily for 8 weeks.
Body weight were recorded on day 1 before administration of OLZ and Vit E, and at the end of the experiment. Testes weight were measured. Sperm count and sperm motility were evaluated. Testosterone hormone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in serum.
Testicular tissue oxidative stress biomarkers were evaluated as malondialdhyde (MDA) and antioxidant enzymes as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). Histopathological analysis of testicular tissue were performed.
Results: Olanzapine resulted in toxicity on adult male albino rats and testicular degeneration in a dose dependent manner as OLZ administration resulted in weight loss in studied animal groups in higher doses compared to that of the control group. It significantly reduced testes weight especially in the highest dose, also, sperm count and motility, serum testosterone hormone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in OLZ administered groups showed significant decrease in comparison to the control group.
In addition to significant increase in MDA level in testicular tissue in OLZ administered groups compared to that of the control group and significant increase in MDA level in testicular tissue in OLZ 10 mg/kg compared to OLZ 5 mg/kg and OLZ 2.5 mg/kg. Also, the results showed a significant decrease in SOD, GSH and CAT in testicular tissue in all groups received Olanzapine compared to that of the control group and showed significant decrease in higher doses compared to lower doses of OLZ.
The results showed that coadministration of Vit E with OLZ 5mg/kg resulted in significant improvement in body weight compared to OLZ 5mg/kg alone, Sperm count, motility, testosterone hormone, FSH and LH levels results were improved especially in group 6 and 7 compared to that of group 3 and 4. Also, Vit E administration resulted in significant improvement in all oxidative stress biomarkers in groups no 5, 6 and 7 compared to that of groups no 2, 3 and 4 which received OLZ alone.
Histopathological changes observed in seminiferous tubules in the form of testicular degeneration and vacuolation which are marked in OLZ10mg/kg. These toxicity may be related to oxidative stress and hyperprolactinemia, and it was found that the antioxidant effect of Vit E could ameliorate theses toxic effects.
In conclusion,coadministration of Vit E with OLZ may have a protective effect against its reproductive toxicity by improving oxidative stress which appeared in increasing CAT, SOD, GSH and decreasing MDA levels in tissue.
In order to be able to fully investigate the toxic effect of OLZ on reproductive system and the protective effect of Vitamin E, further studies with more high doses and longer duration are recommended.