Impact of Methotrexate and Leucovorin on Hormonal Regulated Enzymes of Carbohydrate Metabolism in Accessory Reproductive Tissues of Ovariectomized Rats

Abstract

Background: Female reproductive tract cells are fast proliferating like cancer cells. Methotrexate (MTX), an anticancer drug when used to treat non-neoplastic diseases in young women results in deleterious effects leading to infertility. Oviduct, uterus, cervix and vagina depend on ovary for their structural and functional sustenance. Ovarian ablation followed by chemotherapy in premenopausal women is a common practice in the treatment of cancer. Hence, methotrexate effect on reproductive organs in Ovariectomized (OVX) rats was investigated. Objective: To reveal the direct influence of MTX on estradiol and progesterone in OVX rats. Also, the protective role of leucovorin (LCN) an antidote to MTX, estradiol (E2) and progesterone (P) replacement was investigated. Methods: Animals were randomly divided into the following groups (n=6): group 1: OVX, group 2: OVX+MTX, group 3: OVX+MTX+LCN, group 4: OVX+E2, OVX+MTX+LCN+E2, group 5: OVX+P, group 6: OVX+MTX+LCN+P, treated once/day intramuscularly (im) for 4 days and sacrificed on day 5. At the end of the experiment reproductive 24 tract tissues oviduct, uterus, cervix and vagina were used for total protein, glycogen, Glucose-6-Phosphate Dehydrogenase (G6PD), Lactate Dehydrogenase (LDH) and Alkaline Phosphatase (ALP) enzyme activities. Results: MTX treatment reduced protein, glycogen, G6PD, LDH and ALP activities in oviduct, uterus, cervix and vagina of OVX rats. However, LCN supplementation was partially protective on some enzymes, which was tissue dependent. Hormonal replacement improved protein and enzyme levels in all the tissues. Estradiol treatment showed a distinct enhancement over progesterone in elevating such levels. However, MTX and LCN in a combination treatment with steroids reversed the activities of enzymes in all the tissues.