LIPID-PEROXIDATION AND LYSOSOMAL INTEGRITY IN DIFFERENT INFLAMMATORY MODELS IN RATS - THE EFFECTS OF INDOMETHACIN AND NAFTAZONE

In the present study, the potential involvement of lipid peroxidation and disruption of lysosomal integrity in the pathogenesis of different experimental models of inflammation was examined. The chosen models w ere carrageenan-induced paw oedema, carrageenan granuloma pouch (acute phase) and Freund's adjuvant-induced arthritis in rats. The pharmacol ogical and biochemical effects of naftazone, a lysosomal membrane stab ilizer and indomethacin, a standard anti-inflammatory agent were evalu ated with regard to paw oedema volume, serum and exudate activities of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG), in additi on to serum and liver lipid peroxide (LP) levels. Intraperitoneal admi nistration of the test drugs, in rats subjected to inflammation, produ ced: (1) a significant inhibition of carrageenan-induced paw oedema, ( 2) a marked reduction of the paw oedema of the Freund's adjuvant arthr itic animals, (3) a remarkable decrease of lysosomal leakage of NAG in to the exudate of carrageenan granuloma pouch, (4) a slight, but signi ficant, reduction of NAG activity in the serum of rats subjected to ca rrageenan inflammation, and (5) a reduction of the serum level of LP t hat was elevated in adjuvant-induced arthritic rats. The level of live r LP was altered by either drugs in an opposite manner; while naftazon e lowered hepatic LP, indomethacin markedly elevated its level. The re sults of the present investigation revealed that lipid peroxidation an d disruption of lysosomal integrity are implicated in the pathogenesis of inflammatory processes, and the protection against these deleterio us effects imparted both drugs significant anti-inflammatory activity. (C) 1995 The Italian Pharmacological Society