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Published on: September 12, 2019
Silymarin attenuates mycophenolate mofetil-induced duodenal disorders in rats
Hassan Malekinejad1, Sanaz Sheikhzadeh1, Rahim Hobbenaghi2
1Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, I. R. Iran.
Objective:
The protective effect of silymarin (SMN) on mycophenolate mofetil (MMF)-induced duodenal disorders was investigated.
Materials And Methods:
Forty-two Wistar rats were assigned to seven groups including control and test groups. The control animals received saline and the test animals were treated with MMF (30 mg/kg, orally) and saline, MMF and SMN (25, 50, and 100 mg/kg, orally), MMF and Celecoxib (CLX, 50 mg/kg, orally), and MMF and SMN plus CLX for 14 consecutive days. The antioxidant status and myeloperoxidase activity were determined and the histopathological examinations on duodenal section also were performed.
Results:
Biochemical analyses revealed that SMN and CLX individually and in combination therapy could reduce the MMF-increased nitric oxide (NO) content, myeloperoxidase (MPA) activity, and malondialdehyde (MDA) level, while the MMF-reduced level of total thiol molecules (TTM) was increased significantly (p<0.05) by given compounds. Concurrent administration of SMN and CLX resulted in a synergistic effect on the reduction of MDA level and MPO activity. SMN and CLX were able to improve the MMF-induced histopathological damages including the villus atrophy and inflammatory cells infiltration.
Conclusion:
Our data suggest that the MMF-induced duodenal disorders may attribute to the elevated NO and MDA levels and myeloperoxidase activity that resulted in pathological injuries. Moreover, the biochemical alterations and histopathological injuries due to MMF administration were reduced by SMN alone or in combination with CLX indicating its protective effect.
Insights
Silymarin (SMN) protects against duodenal damage caused by mycophenolate mofetil (MMF). SMN, alone or with Celecoxib (CLX), reduced MMF-induced biochemical changes and improved gut tissue health.
Area of Science:
- Pharmacology
- Gastroenterology
- Toxicology
Background:
- Mycophenolate mofetil (MMF) is an immunosuppressant with known gastrointestinal side effects.
- Duodenal disorders are a significant concern for patients on MMF therapy.
- Silymarin (SMN) is a natural compound with antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the protective effects of silymarin (SMN) against mycophenolate mofetil (MMF)-induced duodenal damage in a rat model.
- To evaluate the potential synergistic effect of SMN in combination with Celecoxib (CLX).
Main Methods:
- Wistar rats were administered MMF orally for 14 days.
- Test groups received MMF with varying doses of SMN, CLX, or a combination of SMN and CLX.
- Biochemical markers (nitric oxide, malondialdehyde, total thiol molecules), myeloperoxidase activity, and histopathological changes in the duodenum were assessed.
Main Results:
- MMF administration significantly increased nitric oxide, malondialdehyde, and myeloperoxidase activity, while decreasing total thiol molecules.
- SMN and CLX, both individually and in combination, attenuated these MMF-induced biochemical alterations.
- Concurrent administration of SMN and CLX demonstrated a synergistic effect in reducing malondialdehyde and myeloperoxidase activity.
- Histopathological examination revealed that SMN and CLX improved MMF-induced villus atrophy and inflammatory cell infiltration.
Conclusions:
- MMF-induced duodenal disorders are associated with increased oxidative stress (elevated nitric oxide and malondialdehyde) and inflammation (myeloperoxidase activity).
- Silymarin exhibits a protective effect against MMF-induced duodenal injury by mitigating biochemical changes and improving histopathological outcomes.
- Combination therapy with silymarin and Celecoxib may offer enhanced protection against MMF-induced duodenal toxicity.
