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Protective effect of pentoxyfilline in renal toxicity after methotrexate administration

I Asvadi1, B Hajipour, A Asvadi

  • 1Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

European Review for Medical and Pharmacological Sciences
|October 22, 2011
PubMed
Abstract

Insights

Pentoxifylline (PTX) protects against Methotrexate (MTX)-induced kidney damage by reducing oxidative stress and inflammation. This study demonstrates PTX

Area of Science:

  • Nephrology
  • Pharmacology
  • Toxicology

Background:

  • Methotrexate (MTX) treatment can cause nephrotoxicity, a significant clinical concern.
  • Pentoxifylline (PTX) possesses anti-inflammatory and antioxidant properties.
  • This study investigates PTX's potential to mitigate MTX-induced renal damage.

Purpose of the Study:

  • To evaluate the protective effects of Pentoxifylline (PTX) against Methotrexate (MTX)-induced nephrotoxicity in a rat model.
  • To explore the underlying mechanisms involving TNF-alpha downregulation and improved cellular antioxidant activity.

Main Methods:

  • Forty-five male Wistar rats were divided into three groups: control, MTX-treated, and MTX + PTX-treated.
  • MTX (20 mg/kg) was administered intraperitoneally; PTX (50 mg/kg) was given for 3 days prior to and 6 days after MTX.
  • Renal tissues and serum were collected for biochemical and histological analysis, including oxidative stress markers and TNF-alpha levels.

Main Results:

  • MTX administration significantly increased renal tissue injury, apoptosis (TUNEL-positive cells), malondialdehyde (MDA) levels, and serum BUN and creatinine.
  • Simultaneously, MTX treatment reduced glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities.
  • PTX co-administration significantly attenuated these MTX-induced detrimental effects, lowering MDA, BUN, creatinine, and TNF-alpha, while preserving GPx and SOD activity.

Conclusions:

  • MTX-induced renal toxicity appears to be related to direct cellular damage rather than folate synthesis inhibition.
  • Pentoxifylline (PTX) demonstrated significant renoprotective effects against MTX toxicity by reducing oxidative stress and apoptosis.
  • Further research is warranted to fully elucidate the mechanisms of MTX nephrotoxicity and PTX's protective role.

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