Modulation of Arachidonic Acid Metabolism by Olsalazine and Other Aminosalicylates in Leukocytes

Abstract

We investigated the action of the new aminosalicylate olsalazine (disodium azo-disalicylate) on arachidonic acid metabolism in comparison with 5-aminosalicylic acid (5-ASA) and sulphasalazine (SASP) by in vitro incubation of cellular homogenates from human polymorphonuclear (PMNL) and mononuclear (MNL) leukocytes with ¹⁴C-labelled arachidonic acid. Olsalazine reduced the synthesis of leukotriene B₄(LTB₄), 5-hydroxyeicosatetraenoic acid (5-HETE), 11-HETE, 12-HETE, and 15-HETE in PMNL and MNL slightly less than SASP. 5-ASA was significantly less inhibitory than olsalazine and SASP on the formation of lipoxygenase products in PMNL and on LTB₄ synthesis in MNL. In contrast, in MNL the formation of 5-HETE was unaffected, and the production of 11-HETE, 12-HETE, and 15-HETE was even slightly activated by 5-ASA. Total prostaglandin synthesis was dose-dependently reduced by the aminosalicylates (SASP>olsalazine>5-ASA), but only SASP markedly altered the prostaglandin (PG) profile, with an increase in PGE₂ and PGF_2α at the expense of other cyclooxygenase products. It may be concluded that olsalazine resembled SASP with regard to the inhibition of the lipoxygenase but had effects intermediate between the other salicylates on cyclooxygenase. Furthermore, the alteration of the prostaglandin profile by SASP points to an overlying cofactor effect of this drug.

Key Words:

• 5-Aminosalicylic acid
• azodisalicylate
• granulocytes
• human
• leukotrienes
• mononuclear cells
• prostaglandins
• sulphasalazine