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 were carrageenan-induced paw oedema, carrageenan granuloma pouch (acute phase) and Freund's adjuvant-induced arthritis in rats. The pharmacological and biochemical effects of naftazone, a lysosomal membrane stabilizer and indomethacin, a standard anti-inflammatory agent were evaluated with regard to paw oedema volume, serum and exudate activities of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG), in addition to serum and liver lipid peroxide (LP) levels. Intraperitoneal administration of the test drugs, in rats subjected to inflammation, produced: (1) a significant inhibition of carrageenan-induced paw oedema, (2) a marked reduction of the paw oedema of the Freund's adjuvant arthritis animals, (3) a remarkable decrease of lysosomal leakage of NAG into the exudate of carrageenan granuloma pouch, (4) a slight, but significant, reduction of NAG activity in the serum of rats subjected to carrageenan inflammation, and (5) a reduction of the serum level of LP that was elevated in adjuvant-induced arthritic rats. The level of liver LP was altered by either drugs in an opposite manner; while naftazone lowered hepatic LP, indomethacin markedly elevated its level. The results of the present investigation revealed that lipid peroxidation and disruption of lysosomal integrity are implicated in the pathogenesis of inflammatory processes, and the protection against these deleterious effects imparted both drugs significant anti-inflammatory activity.
Agha
A M
AM
Department of Pharmacology, Cairo University, Egypt.
Gad
M Z
MZ
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant; D006099:Granuloma / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009285:Naphthoquinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009285:Naphthoquinones; C005272:naftazone; D002351:Carrageenan; D005620:Freund's Adjuvant; D000118:Acetylglucosaminidase; D007213:Indomethacin