Protective effects of inhaled carbon monoxide in endotoxin-induced cholestasis is dependent on its kinetics
Jazyk angličtina Země Francie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24148277
DOI
10.1016/j.biochi.2013.10.009
PII: S0300-9084(13)00358-1
Knihovny.cz E-zdroje
- Klíčová slova
- Carbon monoxide, Cholestasis, Endotoxin, Heme oxygenase,
- MeSH
- cholestáza chemicky indukované farmakoterapie metabolismus patologie MeSH
- exprese genu MeSH
- hemová oxygenasa (decyklizující) genetika metabolismus MeSH
- interleukin-10 genetika metabolismus MeSH
- interleukin-6 genetika metabolismus MeSH
- játra účinky léků metabolismus patologie MeSH
- krysa rodu Rattus MeSH
- lipopolysacharidy MeSH
- messenger RNA genetika metabolismus MeSH
- oxid uhelnatý farmakokinetika farmakologie MeSH
- poločas MeSH
- potkani Wistar MeSH
- TNF-alfa genetika metabolismus MeSH
- transportní proteiny genetika metabolismus MeSH
- žluč chemie MeSH
- žlučové cesty účinky léků metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hemová oxygenasa (decyklizující) MeSH
- Hmox1 protein, rat MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-6 MeSH
- lipopolysacharidy MeSH
- messenger RNA MeSH
- oxid uhelnatý MeSH
- TNF-alfa MeSH
- transportní proteiny MeSH
Carbon monoxide (CO), a product of heme oxygenase (HMOX), has many beneficial biological functions and is a promising therapeutic agent for many pathological conditions. However, the kinetics of inhaled CO and its protective role in endotoxin-induced cholestasis is not fully known. Thus, our objective was to characterize the kinetics of inhaled CO and then investigate its use in early phase experimental endotoxin-induced cholestasis. Female Wistar rats were randomly divided into 4 groups: CON (control), LPS (lipopolysaccharide, 6 mg/kg), CO (250 ppm COx1h), and CO + LPS. Rats were sacrificed at 0-12 h after LPS administration. Tissues and blood were collected for liver injury markers and tissue CO distribution measurements. Livers were harvested for measurements of Hmox activity, Hmox1 mRNA expression, cytokines (IL10, IL6, TNF), and bile lipid and pigment transporters. Half-lives of CO in spleen, blood, heart, brain, kidney, liver, and lungs were 2.4 ± 1.5, 2.3 ± 0.8, 1.8 ± 1.6, 1.5 ± 1.2, 1.1 ± 1.1, 0.6 ± 0.3, 0.6 ± 0.2 h, respectively. CO treatment increased liver IL10 mRNA and decreased TNF expression 1 h after LPS treatment and prevented the down-regulation of bile acid and bilirubin hepatic transporters (Slc10a1, Abcb11, and Abcc2, p < 0.05), an effect closely related to the kinetics. The protective effect of CO against cholestatic liver injury persisted even 12 h after CO exposure, as shown by attenuation of serum cholestatic markers in CO-treated animals. CO exposure substantially attenuated endotoxin-induced cholestatic liver injury and was directly related to the kinetics of inhaled CO. This data underscores the importance of the kinetics of inhaled CO for the proper design of experimental and clinical studies of using CO as a treatment strategy.
Department of Pediatrics Stanford University School of Medicine Stanford CA USA
Institute of Pharmacology 1st Faculty of Medicine Charles University Prague Prague Czech Republic
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