Effect of methotrexate administration on status of some essential trace elements and antioxidant enzymes in pregnant rats in late gestation

Objective:Folate antagonists are widely used in the treatment of various cancerous states. Paucity of data on effect of administration of one such widely used drug, methotrexate (MTX), on the status of essential trace elements and antioxidant enzymes in pregnant women or in pregnant animals prompted us to undertake this study.

Methods:MTX at a concentration of 5 mg/kg body weight was administered intraperitoneally as single dose to pregnant Sprague-Dawley rats for three consequitive days from day 17 of pregnancy. Control group of pregnant rats received single dose of saline instead of the anti-cancer drug on all the 3 days. After receiving the third dose of drug, the treated rats and control group rats were sacrificed, 1 h after intraperitoneal injection of a cocktail of essential trace elements namely, Cu, Se and Zn administered as a single bolus dose. Blood samples were collected 30 min of trace element cocktail injection, after decapitation and concentrations of trace elements in serum samples were determined by atomic absorption spectrophotometry. Concentrations of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and total antioxidant status were determined by specific analytical kits, using spectrophotometry.

Results:In control group(n = 6), serum concentrations of Cu, Se and Zn averaged 2330.5, 614.8 and 2773.2 microg/l, while in study group (n = 6) the concentrations of trace elements averaged 2294, 596 and 2713 microg/l, respectively. Student's t-test did not show any statistical significance (p > 0.05) between various trace element concentrations in control and treated groups. Cu:Zn ratios of control and treated group of rats did not vary significantly as well. Concentrations of superoxide dismutase, glutathione peroxidase in whole blood samples in control rats averaged 165 and 43,260 U/ml, respectively, while in MTX-treated group of animals the corresponding antioxidant enzymes averaged 330.6 and 67,101 U/ml respectively. SOD and GPX values were significantly higher in drug-treated animals compared to controls (Student's t-test, p < 0.05) However, total antioxidant activity was shown to be significantly lower (Student's t-test; p < 0.05) in the drug-treated group compared to control.

Conclusions:We report for the first time that effect of MTX administration in pregnancy is not associated with significant alteration in disposition of essential trace elements. However, the effect of drug administration on antioxidant enzyme status in pregnant women cannot be excluded while using the drug in clinical states.