Possible ameliorative effect of human placental extract on methotrexate-induced nephrotoxicity in albino rats

Background Methotrexate (MTX) is one of chemotherapeutic drugs that induce several side effects. The present study aimed to investigate the ameliorative effect of human placental extract (HPE) against MTX-induced nephrotoxicity in rats. In this study, forty adult male albino rats were equally divided into four groups. Control group: rats were daily injected intraperitoneally with physiological saline (0.5 ml for each rat) for 5 days, HPE group: rats were subcutaneously injected with HPE at a dose level of 10.08 mg/Kg b.w/day for 2 weeks, MTX group: rats were intraperitoneally injected with MTX at a dose level of 5 mg/Kg b.w/day for 5 consecutive days, MTX and HPE group: rats were intraperitoneally injected with MTX (at the same dosage of MTX group) for 5 days and at the same time they were subcutaneously injected with HPE (at an exact dosage of HPE group), daily for 2 weeks. Twenty-four hours after the last dose for each treatment, rats were killed and blood samples were collected for determination of urea, creatinine, sodium (Na+) and potassium (K+) levels. Kidney tissues were taken for histological examination and immunohistochemical staining of both cysteine-aspartic protease-3 (caspase-3) and proliferating antigen Ki-67 (Ki-67) expressions. Results From the obtained data, MTX induced nephrotoxicity through a highly significant increase in urea, creatinine, Na+ and K+ levels compared with the control group. In addition to massive histological alterations, a highly significant increase in caspase-3 expression and a significant decrease in Ki-67 expression were observed. On the other hand, injection with HPE ameliorated urea, creatinine, Na+ and K+ levels comparing to MTX group. Moreover, HPE markedly improved the histological and immunohistochemical changes resulted from MTX treatment. Conclusions It is concluded that HPE ameliorated the nephrotoxicity induced by MTX.