Effect of chenodeoxycholic acid and sodium hydrogen sulfide in dinitro benzene sulfonic acid (DNBS)--Induced ulcerative colitis in rats.
BACKGROUND
Ulcerative colitis is a chronic inflammatory condition in which the inflammatory response confined to the colon. There is a need to explore the new targets for UC such as Farnesoid X receptor and hydrogen sulfide pathway.


METHODS
Wistar rats of either sex (200-250 g) were used. 2,4-Dinitrobenzene sulfonic acid (DNBS) (25mg/rat) given by rectal route into the colon to induced symptoms of ulcerative colitis. Chenodeoxycholic acid (CDCA) (10 and 20mg/kg) and sodium hydrogen sulfide (NaHS) (10 and 30 μmol/kg) and a inhibitor of cystathionine-γ-lyase enzyme (CSE) i.e. dl-propargylglycine (10mg/kg) treatment given along with 2,4-dinitrobenzene sulfonic acid. The disease activity index was assessed by daily change in body weight and rectal bleed score and change in length of colon. Oxidative stress markers (reduced glutathione, malondialdehyde (MDA), nitrite, and catalase and myeloperoxidase enzyme activity), serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels in blood serum, and cardiac hemodynamic were performed on last day.


RESULTS
The administration of DNBS intra-rectally in rats produced loss of body weight and bloody diarrhea with significant increase in oxidative stress markers in the colon. CDCA (10 and 20mg/kg) and NaHS (10 and 30 μmol/kg) significantly attenuated DNBS-induced UC in rats. The combination of CDCA (10mg/kg) and NaHS (10 μmol/kg) showed synergetic effect whereas; dl-propargylglycine reversed the protective effect of CDCA.


CONCLUSIONS
The observed beneficial effects following CDCA may be due to its action through activation of CSE enzyme which leads to hydrogen sulfide generation.
Department of Pharmacology, I.S.F College of Pharmacy, Moga, India.
Nidhi
N
Goyal
Department of Pharmacology, I.S.F College of Pharmacy, Moga, India.
Ajay
A
Rana
Department of Pharmacology, I.S.F College of Pharmacy, Moga, India.
Krishna Reddy V
KR
Bijjem
Department of Pharmacology, I.S.F College of Pharmacy, Moga, India. Electronic address: punnubansal79@gmail.com.
Puneet
P
Kumar
D000818:Animals; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives* / Q000633:toxicity; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000008:administration & dosage*; D016896:Treatment Outcome
D013440:Sulfides; D002635:Chenodeoxycholic Acid; C045305:2,4-dinitrofluorobenzene sulfonic acid; D004139:Dinitrofluorobenzene; C025451:sodium bisulfide
2,4-Dinitrobenzene sulfonic acid; Farnesoid X receptor; Hydrogen sulfide; Oxidative stress; Ulcerative colitis