Anti-Implantation Activity of Methtrexate and Leucovorin in Albino Rats

Abstract

Background.The loss of reproductive function is one of the most important adverse effects of chemotherapy. Folic acid deficiency may be harmful in pregnancy. Hence, it is imperative to investigate if leucovorin (LCN), a folinic acid supplementation and withdrawal of MTX treatment facilitate maintenance of pregnancy in albino rats.Aim. The aim of this study was to examine the role of leucovorin (LCN) and withdrawal of MTX treatment in the protection of pregnancy at very early stage of pregnancy in MTX treated rats.Animals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows: Control, MTXLD (low dose), MTXHD (high dose), MTXHD + LCN (leucovorin), and MTXHD + WD (withdrawal). Animals were treated intramuscularly (im) on days 1-5 of pregnancy. MTXHD treatment was withdrawn and female rats showing regular cycle were caged with male rats. Laparotomy was performed on day 8 of pregnancy to note the number of implantation sites. Rats were sacrificed on day 20.Results. MTX significantly reduced maternal weights, number of corpora lutea, and implantation sites. 100% foetal resorption was prevalent in MTX treated groups. LCN supplementation did not help maintain pregnancy. While approximately 45% foetal resorption was observed in withdrawal group.

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

“…We reported the histopathological differences in ovary, oviduct, uterus, cervix and vagina to be MTX dose dependent [1]. Recently, we also reported the anti-implantation activity of MTX and alterations in glycogen content in ovary, oviduct, uterus, cervix and vagina of rats caused by MTX [29,30]. On the other hand, sustainable benefits following chemotherapy with ovarian ablation technique during early and advanced stages of cancer remains ambiguous till date.…”

“…Spectrophotometrically O.D was recorded at 620 nm. The amount of glucose was converted to glycogen by dividing with the Morris factor 1.11 [30].…”

“…Female accessory reproductive tissues (oviduct, uterus, cervix and vagina) are known to be dependent on ovarian steroids for their normal structure and function. Recent research from our group suggests drastic effects of MTX on female reproductive tract [1] and its anti-implantation activity [30]. Also, our previous studies show that ovariectomy, MTX and LCN treatments is known to cause variations in the structure and function of reproductive tract, a reduction in body and organ weights and antiestrogenic and antiprogestational [28] properties.…”