title: Mycophenolate mofetil alters the antioxidant status in duodenum of rats: Implication for silymarin usage in mycophenolate mofetil-induced gastrointestinal disorders.
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.
authors: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
authors: Sanaz
authors: S
authors: Sheikhzadeh
authors: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran;
authors: Hassan
authors: H
authors: Malekinejad
authors: Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors: Rahim
authors: R
authors: Hobbenaghi
keywords: Antioxidant status; Gastro-protective effect; Gastrointestinal disorders; Mycophenolate mofetil; Silymarin
references: Indian J Clin Biochem. 2010 Apr;25(2):169-74
references: 23105905
references: Clin Biochem. 2000 Mar;33(2):107-13
references: 10751588
references: Transplant Proc. 2007 May;39(4):1278-9
references: 17524953
references: Transplant Proc. 2011 Sep;43(7):2741-6
references: 21911156
references: Cell Biochem Funct. 1997 Mar;15(1):27-33
references: 9075334
references: Front Biosci. 1999 Mar 15;4:D286-98
references: 10077541
references: Hum Exp Toxicol. 2012 Sep;31(9):921-30
references: 22354081
references: Evid Based Complement Alternat Med. 2006 Dec;3(4):469-73
references: 17173110
references: World J Gastroenterol. 2005 Apr 28;11(16):2371-84
references: 15832404
references: Eur J Biochem. 1968 Oct 17;6(1):126-30
references: 4387188
references: Biochem Pharmacol. 1990 Jun 15;39(12):2027-34
references: 2353942
references: Phytother Res. 2012 May;26(5):709-15
references: 22016029
references: Chem Biol Interact. 2003 May 6;145(2):117-37
references: 12686489
references: Mol Vis. 2010 Oct 01;16:1913-9
references: 21031014
references: Planta Med. 2001 Feb;67(1):94-6
references: 11270735
references: Drug Saf. 2001;24(9):645-63
references: 11522119
references: Am J Gastroenterol. 1998 Feb;93(2):139-43
references: 9468229
references: Life Sci. 2010 Aug 28;87(9-10):309-15
references: 20637780
references: J Surg Res. 2008 Apr;145(2):214-22
references: 17950327
references: Liver Transpl. 2006 Sep;12(9):1342-6
references: 16741931
references: Biochem Pharmacol. 2002 Sep;64(5-6):1019-26
references: 12213601
references: Transplant Proc. 2001 May;33(3):2237-8
references: 11377513
references: Drugs. 2001;61(14):2035-63
references: 11735632
references: Trends Biochem Sci. 1990 Apr;15(4):129-35
references: 2187293
references: Ther Drug Monit. 2003 Feb;25(1):1-16
references: 12548138
references: Eur J Clin Pharmacol. 2010 Jul;66(7):671-9
references: 20473489
references: Am J Transplant. 2004;4 Suppl 9:72-80
references: 15113356
references: Hum Exp Toxicol. 2005 Nov;24(11):597-601
references: 16323577
references: Transplantation. 2003 Mar 15;75(5):665-72
references: 12640307
references: Transplant Proc. 2006 Dec;38(10):3323-6
references: 17175262
references: Methods Enzymol. 1999;299:15-27
references: 9916193
references: Phytomedicine. 2009 May;16(5):391-400
references: 19303273
references: Transplant Proc. 2007 Sep;39(7):2190-3
references: 17889134
references: Clin Transplant. 1996 Feb;10(1 Pt 2):77-84
references: 8680053
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: Nephrol Dial Transplant. 2002 May;17(5):923-6
references: 11981085
references: Gut. 1993 Jul;34(7):865-8
references: 8344570
references: Transpl Int. 2004 Sep;17(8):463-7
references: 15322747