Zidovudine potentiates local and systemic inflammatory responses in the rat.
The effect of chronic treatment with zidovudine (AZT) on the inflammatory response was examined in the rat. AZT was administered orally for 36 days. On day 35, inflammation was induced by hindpaw injection of 1% carrageenan lambda. Paw edema over a 24-hour period was used as a marker of the local inflammatory reaction. On day 36, quantification of immunoreactive T-kininogen and alpha 1-inhibitor-3 in liver and serum was used to assess the systemic inflammatory response. Albumin was selected as a protein whose concentration is modified only slightly or not at all during the acute-phase response. Animals treated with AZT transiently exhibited significantly greater (18%) paw edema 3 hours after carrageenan injection. AZT treatment alone induced a 1.8-fold increase in serum T-kininogen concentration, but it had no effect on albumin and alpha 1-inhibitor-3. In rats with inflamed paws, AZT administration led to a significant increase in liver (3.4-fold) and serum (1.8-fold) immunoreactive T-kininogen content. Dot blot analysis of total RNA isolated from liver correlated with the protein measurements. Our results indicate that chronic treatment with AZT potentiates the nonspecific local and the systemic inflammatory responses in the rat.
Raymond
P
P
Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Blais
C
C
Décarie
A
A
Morais
R
R
Adam
A
A
D000209:Acute-Phase Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D003576:Electron Transport Complex IV / Q000032:analysis; D005079:Excipients / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D007704:Kininogens / Q000097:blood / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D011480:Protease Inhibitors / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012709:Serum Albumin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D019380:Anti-HIV Agents; D005079:Excipients; D007704:Kininogens; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D012709:Serum Albumin; C017894:alpha 1-inhibitor 3; D015215:Zidovudine; D002351:Carrageenan; D003576:Electron Transport Complex IV