Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats.
The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE(2) concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE(2) concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60-240 mg/kg), and paracetamol (100-200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE(2) concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE(2) in this response.
Kanashiro
Alexandre
A
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Pessini
Andréa C
AC
Machado
Renes R
RR
Malvar
David do C
Ddo C
Aguiar
Fernando A
FA
Soares
Denis Melo
DM
do Vale
Mariana L
ML
de Souza
Glória E Petto
GE
D000082:Acetaminophen / Q000494:pharmacology / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000134:cerebrospinal fluid / Q000139:chemically induced* / Q000188:drug therapy; D001831:Body Temperature / Q000187:drug effects*; D000068579:Celecoxib; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004177:Dipyrone / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000134:cerebrospinal fluid / Q000139:chemically induced* / Q000188:drug therapy; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D015054:Zymosan / Q000008:administration & dosage / Q000009:adverse effects*
D018712:Analgesics, Non-Narcotic; D011720:Pyrazoles; D013449:Sulfonamides; D000082:Acetaminophen; D004177:Dipyrone; D003907:Dexamethasone; D015054:Zymosan; D000068579:Celecoxib; D015232:Dinoprostone; D007052:Ibuprofen