Role of erythropoietin in methotrexate-induced nephrotoxicity in adult male albino rats

Abstract

Introduction: Methotrexate (MTX) could provoke a renal dysfunction. However, beneficial extra-hematopoietic effect of erythropoietin might guard against MTX-induced nephrotoxicity. Objectives: Determination of renoprotective erythropoietin’s role against MTX-induced nephrotoxicity through elucidating its renofunctional and renomorphological effects in adult male albino rats. Materials and Methods: The study was performed on 60 adult male Albino rats, equally divided into three groups; group 1 (control): treated with intraperitoneal injections of normal saline at a dosage of 0.5 mg/kg BW twice weekly for 9 weeks. group 2: injected with MTX hydrate intraperitoneal twice weekly at a dosage of 0.5 mg/kg BW for 9 weeks; and group 3: intraperitoneal injected with MTX hydrate in a similar dosage and duration like group 2 concomitant with subcutaneous injection of 100 IU/kg recombinant human erythropoietin once weekly for 9 weeks. At the study end, serum urea and creatinine together with albuminuria were measured, rats were sacrificed and renal sections were prepared for histopathological examination. Results: Significantly increased values of renal function analyzed substances with deteriorated histopathological renal changes were detected in the MTX-treated group compared to either the control or to the MTX and erythropoietin co-treated group. The later displayed statistically significant decreased levels of the substances accompanied by remarkably ameliorated microscopic renal changes. Additionally, insignificant statistical biochemical and morphological renal differences were noticed between the third and control groups. Conclusion: This study concluded valuable and efficient defense against MTX-induced nephrotoxicity in adult male Albino rats when co-treated with erythropoietin.

Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats

“…This is similar to the findings of other previous studies. 7,8 The exact mechanism of MTX nephrotoxicity was unclear. However, some studies found that the main factor in MTXrelated tissue injury was oxidative damage, with successive generation of more free radicals, the role of oxidative stress has been reported in MTX-induced nephrotoxicity.…”

“…6 Histologically in MTX-treated rats, kidneys showed: enlargement of Bowman capsule cavity, infiltration of lymphocytes, diminish of glomeruli size, an increase in blood cells count and degeneration of tubules. 7,8 Like other drugs with nephrotoxic effects, MTX-induced renal function declination is clinically tested by observation of hematuria and deterioration in serum urea and creatinine level. Reproduction of such effects is done in research studies in animals after a single dose of MTX.…”

“…Histologically in MTX–treated rats, kidneys showed: enlargement of Bowman capsule cavity, infiltration of lymphocytes, diminish of glomeruli size, an increase in blood cells count and degeneration of tubules. 7 , 8 …”

Ginkgo Biloba Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression

“…Chemotherapeutic drugs are broadly used against various kinds of cancer and their clinical use is associated with the occurrence of unfavorable side effects including many organ toxicities [1]. One of these drugs is methotrexate (MTX) which is a folate antagonist used to treat oncologic and non-oncologic conditions like psoriasis and rheumatoid [2].…”

“…Renal impairment developed by the use of MTX was characterized laboratorially by the abrupt rise of serum creatinine and urea with marked elevation of plasma MTX concentration and characterized pathologically by structural changes as degeneration and dilation of renal tubules and glomeruli degeneration [1]. Moreover, the pathogenesis of MTX-induced toxicity involved oxidative stress which played a crucial task in triggering inflammation and apoptosis processes [2,4,5,6].…”