sc-236 and Acute-Disease

We examined the pre-emptive analgesic effect of a cyclooxygenase (COX)-2 inhibitor in a rat surgical pain model and characterised the changes in cutaneous COX-2 around a surgical site. Thermal hyperalgesia and mechanical allodynia were tested in the rats for three days after incision and skin tissues were collected for analysis of COX-2. There was decreased expression of cutaneous COX-2 one day after surgical incision. Pre-incision injection of the COX-2 inhibitor significantly inhibited expression of COX-2 and also reduced thermal hyperalgesia (but not mechanical allodynia) compared with the post-incision COX-2-inhibitor injection group, one day after incision.

Topics: Acute Disease; Analysis of Variance; Animals; Behavior, Animal; Blotting, Western; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Hot Temperature; Hyperalgesia; Male; Pain Management; Pain Measurement; Pain Threshold; Pain, Postoperative; Physical Stimulation; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides

To investigate the effect of selective Cycloo-xygenase-2 (COX-2) inhibitor 4-[5-(4-Chloro-phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-236), on the cholecystokinin (CCK)-octapeptide-induced acute pancreatitis (AP) in rats.. Wistar rat weighing 240 g to 260 g were divided into three groups. (1) Normal DMSO treated group, (2) SC-236 at 4 mg/kg treated group; SC-236 systemically administered via the intravenous (i.v.) catheter, followed by 75 microg/kg CCK octapeptide subcutaneously three times, after 1, 3 and 5 h. This whole procedure was repeated for 5 d. (3) Dimethyl sulfoxide (DMSO) treated group: an identical protocol was used in this group as in the SC-236 cohort (see 2. above). Repeated CCK octapeptide treatment resulted in a typical experimentally induced pancreatitis in the Wistar rats.. SC-236 improved the severity of CCK-octapeptide-induced AP as measured by laboratory criteria [the pancreatic weight/body weight (p.w/b.w) ratio, the level of serum amylase and lipase]. The SC-236 treated group showed minimal histologic evidence of pancreatitis and a significant reduction in myeloperoxidase activity. SC-236 also increased heat shock protein (HSP)-60 and HSP72 compared with the DMSO-treated group in the CCK-octapeptide-induced AP and also reduced the pancreatic levels of COX-2. Furthermore, SC-236 reduced proinflammatory cytokine synthesis and inhibited NF-kappaB activation compared with the DMSO-treated group in the CCK-octapeptide-induced AP.. Our results suggested that COX-2 plays pivotal role in the development of AP and COX-2 inhibitors may play a beneficial role in preventing AP.

Topics: Acute Disease; Animals; Chaperonin 60; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Gene Expression Regulation; HSP72 Heat-Shock Proteins; Interleukin-1; Interleukin-6; Male; NF-kappa B; Pancreas; Pancreatitis; Pyrazoles; Rats; Rats, Wistar; Sincalide; Sulfonamides; Tumor Necrosis Factor-alpha

Nitrergic and prostanoid pathways have both been implicated in inflammatory processes.. To investigate their respective contributions in a rat model of chronic arthritis.. Male Wistar rats (n = 4-6/group) received either an intra-articular injection of 2% carrageenan/4% kaolin (C/K) or intra- and periarticular injections of Freund's complete adjuvant (FCA; 10 mg/ml M tuberculosis). Joint diameter, urinary nitric oxide metabolites (NO(x)), and prostaglandin E(2) (PGE(2)) levels were measured as indices of the inflammatory process. A prophylactic and therapeutic (day 5) dose ranging study of an inducible nitric oxide synthase inhibitor, L-N-(1-iminoethyl)-lysine (L-NIL), and a cyclo-oxygenase-2 (COX-2) inhibitor, SC-236, was performed with the drugs given subcutaneously. Submaximal doses were identified and used for combination studies. Appropriate vehicle controls were included.. L-NIL and SC-236 dose dependently inhibited C/K induced acute joint swelling, the magnitude being greatest when they were given in combination. Both prophylactic and therapeutic administration of SC-236 in the FCA induced model of chronic arthritis produced a dose dependent reduction in all the measures assessed. However, although L-NIL demonstrated similar dose dependent inhibition of urinary NO(x) and PGE(2) levels, joint swelling was significantly exacerbated in this model. Co-administration of the inhibitors nullified the benefits of SC-236.. Whereas COX-2 derived prostaglandins are proinflammatory in both acute and chronic joint inflammation, NO seems to have divergent roles, being anti-inflammatory in chronic and proinflammatory in acute joint inflammation.

Topics: Acute Disease; Animals; Arthritis, Experimental; Carrageenan; Chronic Disease; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Combinations; Enzyme Inhibitors; Isoenzymes; Lysine; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyrazoles; Rats; Rats, Wistar; Sulfonamides