Inhibitory effects of azelastine and tranilast on leukotriene B4 and leukotriene C4 generation by rat colonic mucosa.
Anti-allergic drugs such as sodium cromoglycate are known to be effective for the treatment of ulcerative colitis (UC). Because leukotriene (LT) production is considered to play an important role in the pathophysiology of UC, we examined the effect of the anti-allergic drugs, azelastine and tranilast, and the 5-lipoxygenase inhibitor, AA861, on LTB4 and LTC4 production by isolated rat colonic mucosa treated with the calcium ionophore, A23187. Preincubation of colonic mucosa with AA861 (10(-4) M) or azelastine (10(-4) M) significantly reduced AA23187-induced LTB4 (p < 0.01 and p < 0.05, respectively) and LTC4 (p < 0.01) production. Pretreatment with tranilast (10(-3) M) also significantly reduced A23187-induced LTC4 production (p < 0.05). These findings suggest that azelastine and tranilast can inhibit LT production in colonic mucosa and may be beneficial in the treatment of patients with UC.
Shimizu
T
T
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Yamashiro
Y
Y
Igarashi
J
J
Yabuta
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D017997:Leukotriene C4 / Q000096:biosynthesis*; D008297:Male; D010793:Phthalazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D010793:Phthalazines; D062367:ortho-Aminobenzoates; D007975:Leukotriene B4; D017997:Leukotriene C4; D000001:Calcimycin; C012293:tranilast; C020976:azelastine