Central heme oxygenase-carbon monoxide pathway participates in the lipopolysaccharide-induced tolerance in rats.
Recently, heme oxygenase-carbon monoxide (HO-CO) pathway has been reported to be involved in the development of lipopolysaccharide (LPS) fever. However, no information exists about its participation in LPS tolerance, which is defined by an attenuation of the febrile response to repeated administrations of LPS. Thus, we tested the hypothesis that HO-CO pathway plays a role in endotoxin tolerance, which was induced by means of three consecutive LPS intraperitoneal injections (i.p.) at 24-h intervals. Body temperature (Tb) was measured by biotelemetry. Induction of the HO pathway using intracerebroventricular (i.c.v.) heme lysinate reversed tolerance, and this effect could be prevented by pretreatment with ODQ [a soluble guanylate cyclase (sGC) inhibitor; i.c.v.]. These results indicate that HO-CO pathway seems to be down-regulated during LPS tolerance, and that CO is the HO product that can prevent LPS tolerance, acting via cGMP. In further support, either biliverdine or iron (the others HO products; i.c.v.) had no effect in LPS-induced tolerance.
Raffaini
Maria S
MS
Department of Pediatric Dentistry, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14040-904, SP, Brazil.
Dias
Mirela B
MB
Branco
Luiz G S
LG
D000818:Animals; D001664:Biliverdine / Q000378:metabolism / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000378:metabolism*; D002712:Chlorides; D006152:Cyclic GMP / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology*; D004731:Endotoxins / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007239:Infections / Q000382:microbiology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D007501:Iron / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002712:Chlorides; D004731:Endotoxins; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); D006162:Guanylate Cyclase; D006152:Cyclic GMP; D001664:Biliverdine; C024555:ferric chloride