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Published on: February 9, 2016
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;
Abstract:
Mycophenolate mofetil (MMF) as an immunosuppressive agent is used to prevent graft rejection. One of the adverse effects of long time administration of MMF is the gastrointestinal disorder. This study aimed to investigate the gastroprotective effect of silymarin (SMN) on MMF-induced gastrointestinal (GI) disorders. Twenty-four adult female Wistar rats were assigned into three groups including the control and test groups. The control animals received saline (5 mL kg(-1)) and the test animals were treated with MMF (40 mg kg(-1), orally) and saline, MMF and silymarin (SMN, 50 mg kg(-1), orally) for 14 consecutive days, respectively. To evaluate the GI disorders due to the MMF-induced oxidative stress and subsequently the protective effect of SMN, malondialdehyde (MDA), total thiol molecules (TTM) levels and total anti-oxidant capacity (TAC) were determined. Additionally, histopathological examinations in the duodenal region of small intestine were performed. The MMF-increased level of MDA was reduced by SMN administration, while the MMF-reduced level of TTM increased significantly (p < 0.05) by SMN administration. Histopathological examinations showed the goblet cell reduction and congestion in the MMF-received animals; while SMN was able to improve the MMF-induced goblet cell reduction and congestion. Our data suggest that the MMF-induced GI disorders are characterized by changes in antioxidant status, which presented by the elevation of MDA level and reduction of TTM concentration. Moreover, the improved biochemical alterations and histopathologic damages by SMN indicating its gastroprotective and antioxidant effects.
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.
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