Phological Studies of the Effects of Amodiaquine on the Ovary in Sprague-Dawley Rats

Gbotolorun, S.C (2010-09)

A Thesis Submitted to the School of Postgraduate Studies, University of Lagos

Thesis

The prevalence of female infertility ranges from 7 to 28% depending on the age of the woman. Although the origin and frequency of infertility vary about 40 to 50% of the aetiology of infertility cases is as a result of female factors. Malaria and the treatment of malaria have being a major challenge for decades. A number of antimalarial drugs have been reported to have anti-fertility actions. Amodiaquine (AQ) is an anti-malarial drug and belongs to a class of drugs known as the 4-aminoquinolines. It was removed from the essential drug list in 1990 as a result of hepatoxicity and agranulocytosis that occurred with long- term use. AQ is now making a comeback and is in the spotlight as a partner drug with artemisinins in the World Health Organization (WHO) recommended artemisinin based combination therapies (ACTs). In malaria-endemic regions of the world, self medication with antimalarial drugs is common and it is possible for a person to be treated several times in a year. With the frequency of treatment the risk of adverse events associated with long-term use of AQ may arise. A number of investigators have carried out studies on the effect of AQ on pregnancy and pregnancy outcomes, however, there remains a dearth of literature on the short-term or long-term effect of AQ on the structure and function of the ovary in the non-pregnant female. This study was carried out to investigate the histomorphological changes and responses of the ovary of Sprague-Dawley rats to AQ administration. The study was divided into 4 experimental groups. AQ was given at a dose of 6.0 and 12 mg/kg bw via oral and intraperitoneal routes for 28 days. Vitamin C was administered at a dose of 0.1 mg/kg bw 3 days in a week while Vitamin E was given at a dose of 20 mg/kg bw 5 days in a week. In each of the experiments AQ was administered alone, co-administered with Vitamin C and co-administered with Vitamin E (AQ alone, AQ + Vitamin C and AQ + Vitamin E) according to the treatment protocol. At the end of the experiment all the animals were sacrificed by cervical dislocation. Oestrus cycle was determined using the vaginal smear method and ovulation was determined at 10:00hr on the day of estrus. The ovary was dissected and processed for histology, assayed for superoxide dismutase and catalase activities and also assayed for reproductive hormones (follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL). The result of the oestrous cycle showed that AQ prolonged the length of the oestrous cycle and was statistically significant in the group that received 12 mg/kg bw via intraperitoneal route. Co –administration of AQ + Vitamin C increased the cycle length even further and was statistically significant (p < 0.05) except in the group that received 6 mg/kg bw intraperitoneal route. The ovulation studies showed that AQ reduced the number of ova that was shed in the morning of estrus and was statistically significant (p < 0.05) in the group that received 6.o and 12 mg/kg bw oral route. Histology of the ovary showed that AQ increased the number of atretic follicles when compared with the control. There appeared to be more atretic follicles at 12 mg/kg bw than at 6.0 mg/kg bw AQ. AQ caused reduction in the activities of superoxide dismutase and catalase in the ovary and was statistically significant (p < 0.05) in the groups that received AQ + Vitamin C. The expected surge in FSH, LH and PRL between 5 to 7 p.m. on proestrus that is expected for the follicular rupture that occurs at ovulation was experienced in this study. There was no statistically significant difference in the serum concentration of these hormones when compared with the control group. The results obtained in this study shows that AQ is deleterious to the ovary.