Mycophenolate mofetil alters the antioxidant status in duodenum of rats: Implication for silymarin usage in

Sanaz Sheikhzadeh1, Hassan Malekinejad1, Rahim Hobbenaghi2

  • 1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;

Insights

Silymarin (SMN) demonstrates gastroprotective effects against Mycophenolate mofetil (MMF)-induced gastrointestinal disorders by improving antioxidant status and reducing oxidative stress. This study highlights SMN

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Toxicology

Background:

  • Mycophenolate mofetil (MMF) is an immunosuppressant crucial for preventing graft rejection.
  • Long-term MMF administration can lead to gastrointestinal (GI) disorders, often linked to oxidative stress.
  • Silymarin (SMN), a natural antioxidant, is investigated for its potential protective effects.

Purpose of the Study:

  • To investigate the gastroprotective effect of silymarin (SMN) against MMF-induced GI disorders.
  • To evaluate the impact of SMN on MMF-induced oxidative stress markers in the GI tract.
  • To assess the histopathological changes in the duodenum following MMF and SMN treatment.

Main Methods:

  • Adult female Wistar rats were divided into control, MMF-treated, and MMF + SMN-treated groups.
  • Animals received daily oral treatments of MMF (40 mg/kg) and/or SMN (50 mg/kg) for 14 days.
  • Biochemical assays measured malondialdehyde (MDA), total thiol molecules (TTM), and total antioxidant capacity (TAC).
  • Histopathological examination of the duodenal tissue was performed.

Main Results:

  • MMF administration significantly increased MDA levels and decreased TTM levels, indicating oxidative stress.
  • SMN treatment reduced elevated MDA levels and restored reduced TTM levels in MMF-treated rats.
  • Histopathology revealed goblet cell reduction and congestion in MMF-treated rats, which were ameliorated by SMN.
  • SMN administration showed significant protective effects (p < 0.05) on MMF-induced biochemical and histopathological damage.

Conclusions:

  • MMF-induced GI disorders are associated with significant alterations in antioxidant status, including increased MDA and decreased TTM.
  • Silymarin exhibits notable gastroprotective and antioxidant effects, mitigating MMF-induced GI damage.
  • SMN represents a potential therapeutic agent for managing MMF-associated gastrointestinal adverse effects.