Inhibition of superoxide anion production in non-stimulated guinea pig peritoneal exudate cells by anti-inflammatory drugs

Abstract

Inhibitory effects of anti-inflammatory drugs on the production of superoxide anion (·O 2 − by isolated non-treated guinea pig peritoneal exudate cells (PEC) was studied spectro-photometrically using NADH and lactate dehydrogenase (LDH). Values of ID 50 were; diclofenac sodium (2 × 10 −5M), indomethacin (3 × 10 −5M), oxyphenbutazone (8 × 10 −5M), fenamic acid (1 × 10 −4M), ibuprofen (1 × 10 −4M), benzydamine (3 × 10 −4M), aspirin (10 −3M<) and dexamethasone (10 −3M<). The mechanism of inhibition seemed to block plasma membrane associated NAD(P)H oxidase(s) activity which produces ·O 2 − ID 50 values of other drugs; superoxide dismutase (SOD, 2 × 10 −8M), cytochalasin B(1 × 10 −7M) and NEM (6 × 10 −6M). d-Mannitol radical scavenger), 1,3-diphenyl-isobenzofuran (singlet oxygen scavenger) and sodium azide (mitochondrial electron transport inhibitor and singlet oxygen scavenger) were negative. Superoxide radical itself or oxygen-centered radical(s) derived from ·O 2 − is supposed recently as a rate-limiting factor for prostaglandin (PG) synthetase. Whether the inhibition of non-steroidal anti-inflammatory drug (NSAID) on ·O 2 − production is linked directly to PG biosynthesis or not, ·O 2 − was already demonstrated in our laboratory to make a role for the development of rat carageenan foot oedema. It may serve as a new in vitro sceening method of NSAID, to check the inhibitory potency of a compound on ·O 2 − production by guinea pig PEC.