Effect of infliximab on renal injury due to methotrexate in rat

Area of Science:

• Nephrology
• Pharmacology
• Immunology

Background:

• Methotrexate (MTX) is a vital antifolate drug for treating cancers and inflammatory conditions.
• MTX use is limited by dose-dependent nephrotoxicity.
• Infliximab (IFX) is an anti-tumor necrosis factor-alpha biologic with potential protective effects against drug-induced organ damage.

Purpose of the Study:

• To evaluate the protective effect of infliximab against methotrexate-induced nephrotoxicity in a rat model.
• To investigate the impact of infliximab on key inflammatory markers and kidney function following methotrexate administration.

Main Methods:

• Rats received either methotrexate (20 mg/kg, IP) or methotrexate with a prior dose of infliximab (7 mg/kg, IP).
• Kidney tissues and blood samples were collected 5 days post-methotrexate administration.
• Biochemical assays measured inflammatory cytokines (TNF-α, IL-1β), nitric oxide, adenosine deaminase, and carbonic anhydrase-II activity.
• Histological examination assessed kidney damage.

Main Results:

• Methotrexate administration significantly increased kidney levels of TNF-α, IL-1β, nitric oxide, and adenosine deaminase compared to the infliximab co-treated group.
• Histological damage scores and carbonic anhydrase-II activity were significantly lower in rats that received infliximab prior to methotrexate.
• These findings indicate suppressed cytokine release and altered enzyme activity in the presence of infliximab.

Conclusions:

• Infliximab demonstrates a significant protective effect against methotrexate-induced nephrotoxicity.
• This protection is mediated by the suppression of pro-inflammatory cytokines such as TNF-α and IL-1β.
• Infliximab may also mitigate kidney damage by modulating carbonic anhydrase-II activity and influencing purine metabolism.