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Effect of Sulfasalazine and Prednisolone Against Dextran Induced Ulcerative Colitis in Female Balb/C Mice

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Effect of Sulfasalazine and Prednisolone Against Dextran Induced Ulcerative Colitis in Female Balb/C Mice M.V.Ramana et al. / Journal of Pharmacy Research 2012,5(9),4808-4811 Research Article Available online through ISSN: 0974-6943 http://jprsolutions.info Effect of Sulfasalazine and Prednisolone against dextran induced ulcerative colitis in female balb/c mice Dr. M.V.Ramana2, N.S.V.Mukharjee1, Dr. A. Ramesh, M.Manohar, N.Hindu, T.Vanaja, B.Pavani, N.Santhosh, E.Srikanth, M.Venkatesh, K.Phaneendra, *VVSPC Rao.M *Research scholar, BITS PILANI, Hyderabad campus, Hyderabad,India 1. Assistant professor, G.B.N.Institute of Pharmacy, Hyderabad,India 2. Principal, G.B.N.Institute of Pharmacy, Hyderabad,India Received on:12-06-2012; Revised on: 17-07-2012; Accepted on:26-08-2012 ABSTRACT Sulfasalazine is the most widely prescribed drug for ulcerative colitis (1) (5). Following oral administration of sulfasalazine (5) practically unabsorbed reaches the colon where it is split by colonic bacteria to 5-aminosalicylic acid and sulphapyridine. Prednisolone is absorbed into the blood stream so act indiscriminately throughout whole body. Prednisolone is a corticosteroid which is used in ulcerative colitis. Prednisolone works by preventing or reducing inflammation (4). It is used to treat a number of conditions that are characterized by excessive inflammation. Prednisolone suppresses the immune system (6) (4) and so can be used to treat autoimmune diseases (3) (4). If prolong usage of corticosteroids also leads to their immune system can become weak. The objective of this study was to determine effect of sulfasalazine and Prednisolone against dextran sodium sulphate induced colitis in balb/c mice. We observed the parameters like body weight, colon length, colon weight and IL-6 estimation. We observed there is significant reduction in body weight and colon length and increase in colon weight and IL-6 levels with DSS administration. Our findings suggest that sulfasalazine and Prednisolone produces synergistic effect against dextran sodium sulphate induced ulcerative colitis. Keywords: Dextran sulfate sodium; ulcerative colitis; sulfasalazine; Prednisolone; immune response. INTRODUCTION: Ulcerative colitis (UC) is a typical inflammatory intestinal disease (8) be- creased in the inflamed mucosa of patients with UC. Nuclear factor (NF)-kb longing to the class of inflammatory bowel diseases (IBD) (7). The pathogen- (13) performs a crucial function in the expression of many genes involved in esis of UC is believed to involve the interaction of genetic, immune, and immune and inflammatory responses. Active NF-kb-ikb complexes (14) are environmental factors. UC is associated with intestinal inflammation and sequestered in the cytoplasm. On induction by a variety of stimuli, NF-kB often results in weight loss, diarrhea accompanied by blood and mucus, fever, translocates into the nucleus where it can bind to specific DNA sequences gastric dysmotility and shortening of the colon. Pathogenic hallmarks of UC located in the promoter regions of target genes and activate gene transcrip- include ulceration of the mucosa, blunting and loss of crypts, infiltration of tion, thus, by controlling the transcription of inflammatory cytokine genes, it inflammatory cells. The pathologic changes frequently cause epithelial dys- plays a pivotal role in the regulation of immune and inflammatory cytokine plasia and DNA damage with microsatellite instability. Additionally, pro- genes, it plays a pivotal role in the regulation of immune and inflammatory longed and chronic UC (10) may progress to a colorectal cancer .Thus, to responses (15). Increased DNA-binding capacity of NF-kB associated with develop measures to prevent cancer development in UC patients, it is neces- the secretion of high levels of IL-1 and IL-6 has been reported in macroph- sary to understand the pathogenesis of UC at the molecular and cellular ages of UC patients. NF-kB has been recognized as an ideal target for mo- levels. Current studies on UC have reported that proinflammatory cytokines lecular therapies (16) employed to treat inflammatory diseases. Generally, (11) are involved in the initiation of the inflammatory response in colitis (12). UC is characterized clinically by acute exacerbation and corticosteroids may It was reported that mucosa from patients with UC shows increased expres- not be effective even when administered in high doses. In addition, long term sion of interleukins (IL-1 and IL-6), which are believed to play an integral role use of corticosteroids is often associated with serious adverse effects such as in the pathogenesis of UC. Hence, there is currently a strong interest in hormonal disturbances, peptic ulcers, liver dysfunction and psychological agents that block the generation or activities of inflammatory cytokines (18). problems. The appearance of these adverse effects may necessitate discon- Cyclooxygenase (COXs) have been implicated in a number of physiological tinuation of corticosteroid treatment, there by resulting in acute exacerbation events, including the progression of inflammation, immunomodulation (14) (21). Therefore, an alternative treatment for active UC is necessary to elimi- (9) and transmission of pain. Two COX enzymes have been identified. COX- nate the clinical problems associated with corticosteroid therapy (19). 1 is a constitutive enzyme that is required for the formation of prostaglandins (PGs) protecting the stomach and kidney from damage. COX-2, which is MATERIALS & METHOD: normally expressed at very low levels, can be rapidly induced by a variety of stimuli such as cytokines, growth factors, hormones, and carcinogens and is Animal care and use believed to be responsible for the production of prostaglandins associated Female Balb/c mice of (18-22gm) were purchased from national centre for with mediation of inflammation. COX-2 expression is reported to be in- laboratory sciences, National institute of nutrition, Tarnaka, Hyderabad, In- dia. Animals were housed conventionally in an animal room under controlled *Corresponding author. conditions (18-220c, 55±10 humidity, 12 h day/night cycle) and fed with VVSPC Rao standard diet (NCLAS, Hyderabad). BITS, Pilani Hyderabad Campus, Jawahar Nagar, Acute Model: Shameerpet Mandal, Animals were acclimatized for 4 to 5 days prior to the start of the experi- Hyderabad, 500078, ment. Animals were randomly distributed to various groups based on their Andhra Pradesh.India body weight. They were divided into five experimental groups with five Journal of Pharmacy Research Vol.5 Issue 9.September 2012 4808-4811 M.V.Ramana et al. / Journal of Pharmacy Research 2012,5(9),4808-4811 animals in each group, housed in clean filter top cages under COLON LENGTH standard conditions in a 12 hr dark/12 hr light cycle and fed with standard mouse chow. 4 3.42 3.28 2.9 2.86 Group-1 animals were received normal drinking water, E 3 Group-2 animals were received DSS-5%; 2.14 R Group-3 animals were treated with sulfasalazine (50 mg/kg) along with DSS- T 5%. E M 2 I Group-4 animals were treated with predinisolone (0.25 mg/kg) along with T DSS-5%. N E Group-5 animals were treated with sulfasalazine (25mg/kg) & predinisolone C 1 (0.125 mg/kg) along with DSS-5% Induction of colitis: 0 i Animals were housed in a clean filter-top cage in a specific pathogen-free L S e e n A S in n d M D z lo e environment, and fed with standard chow and water. Animals were acclima- la o r R a s P O i + tized for about 4 to 6 days before starting the experiment. Animals were N as n a l f d lf u r e u randomly distributed into various groups based on their body weights. S P S + + + s s s s s s 1. Animals were divided into 5 groups, of each group containing 5 D D D animals. Group 2. Acute colitis in mice was induced by providing drinking water ad Fig no.2:Changes in colon length of different groups of dextran sulphate libtium containing 5% DSS for 7 days. sodium induced colitis in mice model.Results were as mean+/-SEM. 3. Mice were checked daily for the loss of body weight & Symp- COLON WEIGHT toms. 0.524 4. Sulfasalazine and Predinisolone diluted with water were orally 0.6 administered once a day from day 0 of DSS treatment. 5. On the 7th day, animals were euthanized and the colon was re- 0.382 moved for the measurement of colon length, colon weight and IL- ) 0.352 m 0.4 0.29 6 levels. g ( t h 0.204 RESULTS AND DISCUSSION: g i e 0.2 Table no:1 Different groups of animals and changes in different W parameters. Groups Change in body Colon length Colon 0.0 weight(gms) (cms) weight(gms) i L S e e n A S in n d M D z lo e Normal (negative control) 1.84 3.42 0.204 l a o r R a s P O i + Dss-5% (positive control) 0.86 2.14 0.524 N a s n a lf d lf Dss + Sulfasalazine (50mg/kg) 1.2 2.9 0.332 u re u S P S Dss + Prednisolone (0.25mg/kg) 1.32 2.86 0.352 + + + s s s s s s Dss+Sulfa+Predni(25mg/kg;0.125mg/kg) 1.58 3.28 0.29 D D D Change in body weight GROUP Fig no.3:Changes in colon weight of different groups of dextran sulphate 2.0 sodium induced colitis in mice model.Results were as mean+/-SEM. 250 ue) (gms) IL-6 iss 1.5 t 200 mg weight 1.0 150 *** *** 100 *** 0.5 ge in body 50 entration (Pg/ 0.0 0 Chan Conc DSS DSS Normal Normal Sulfasalzine Sulfasalzine Prednisolone Combination Prednisolone Combination Group Group Fig no.1:Changes in body weight of different groups of dextran sulphate Fig 4:Effect of sulfasalazine and prednisolone on IL-4 in colon.Results were sodium induced colitis in mice model.Results were as mean+/-SEM.
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