Halothane induces oxidative stress and NF-kappaB activation in rat liver: protective effect of propofol.
We investigated the effects of propofol on markers of oxidative stress, nuclear factor kappa B (NF-kappaB) activation and inducible nitric oxide synthase (iNOS) expression in liver of rats treated with halothane under hypoxic conditions. Male Wistar rats received halothane 1%/oxygen 14%, oxygen 14%/propofol 60 mg kg(-1) i.p., or halothane 1%/oxygen 14%/propofol 60 mg kg(-1) i.p. Morphological examination showed complete loss of architecture with massive necrosis of parenchyma in the halothane group, while only minor histological abnormalities were observed in rats receiving halothane plus propofol. The cytosolic concentration of TBARS and the hydroperoxide-initiated chemiluminescence increased significantly in the liver of animals from the halothane group (+62% and +40% versus controls, respectively), and this increase was abolished by propofol administration. Halothane induced a marked activation of NF-kappaB (+180%), and resulted in a significant decrease of the nonphosphorylated form of the inhibitor IkappaBalpha (-53%), while phosphorylated IkappaBalpha protein level was markedly increased (+146%). Propofol administration lowered these effects to +30% (NF-kappaB), -26% (nonphosphorylated IkappaBalpha), and +56% (phosphorylated IkappaBalpha). The increase of iNOS protein level (+59%) induced by halothane was significantly reduced to +22% by additional administration of propofol. Results obtained show that administration of propofol inhibits oxidative stress, NF-kappaB nuclear traslocation and iNOS overexpression in liver of rats receiving halothane. Propofol treatment, by inhibiting the NF-kappaB signal transduction pathway, might block the production of noxious mediators involved in the development of halothane-induced injury.
Brasil
Luis J
LJ
Irmandade Santa Casa de Misericordia, Porto Alegre, Brazil.
San-Miguel
Beatriz
B
Kretzmann
Nelson A
NA
Amaral
Jose L Gomes Do
JL
Zettler
Claudio G
CG
Marroni
Norma
N
González-Gallego
Javier
J
Tuñón
María J
MJ
D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D024202:Electrophoretic Mobility Shift Assay; D006221:Halothane / Q000009:adverse effects*; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D020672:I-kappa B Proteins / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D000975:Antioxidants; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D006221:Halothane; D015742:Propofol