Limits...
Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Kosaka J, Morimatsu H, Takahashi T, Shimizu H, Kawanishi S, Omori E, Endo Y, Tamaki N, Morita M, Morita K - PLoS ONE (2013)

Bottom Line: Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects.Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs.Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

ABSTRACT
Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

Show MeSH

Related in: MedlinePlus

Gene expression of inflammatory mediators in the lungs after hemorrhagic shock and resuscitation (HSR).Lungs from the HSR group rats treated with vehicle or biliverdin (BV) were excised at 3 h after resuscitation and the levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) mRNA were determined by Northern blot analysis. (Left) The autoradiographic signals of RNA blot hybridized with [α-32P] deoxycytidine triphosphate-labeled TNF-α (A) or iNOS (B) cDNA. (Right) Concentrations of TNF-α and iNOS mRNA were expressed as arbitrary units. Data are presented as means ± standard deviation and were statistically evaluated using analysis of variance followed by Tukey–Kramer honestly significant difference test (n = 3 per group). *p<0.05 vs. vehicle/sham; †p<0.05 vs. BV/sham; #p<0.05 vs. vehicle/HSR. Vehicle/sham, vehicle-administered animals subjected to sham surgery; BV/Sham, BV-administered animals subjected to sham surgery; vehicle/HSR, vehicle-administered animals subjected to HSR; BV/HSR, BV-administered animals subjected to HSR.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646791&req=5

pone-0063606-g004: Gene expression of inflammatory mediators in the lungs after hemorrhagic shock and resuscitation (HSR).Lungs from the HSR group rats treated with vehicle or biliverdin (BV) were excised at 3 h after resuscitation and the levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) mRNA were determined by Northern blot analysis. (Left) The autoradiographic signals of RNA blot hybridized with [α-32P] deoxycytidine triphosphate-labeled TNF-α (A) or iNOS (B) cDNA. (Right) Concentrations of TNF-α and iNOS mRNA were expressed as arbitrary units. Data are presented as means ± standard deviation and were statistically evaluated using analysis of variance followed by Tukey–Kramer honestly significant difference test (n = 3 per group). *p<0.05 vs. vehicle/sham; †p<0.05 vs. BV/sham; #p<0.05 vs. vehicle/HSR. Vehicle/sham, vehicle-administered animals subjected to sham surgery; BV/Sham, BV-administered animals subjected to sham surgery; vehicle/HSR, vehicle-administered animals subjected to HSR; BV/HSR, BV-administered animals subjected to HSR.

Mentions: To elucidate the molecular mechanism underlying the anti-inflammatory effects of BV, we examined the effects of BV treatment on the gene expression of the inflammatory mediators such as TNF-α and iNOS using Northern blot analysis. Although mRNA levels of TNF-α and iNOS were barely detectable in the sham groups irrespective of the presence or absence of BV, these genes were significantly upregulated in the vehicle/HSR group 3 h after resuscitation (Fig. 4). The mRNA levels of TNF-α and iNOS were significantly decreased in the BV/HSR group compared with those in the vehicle/HSR group (Fig. 4).


Effects of biliverdin administration on acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Kosaka J, Morimatsu H, Takahashi T, Shimizu H, Kawanishi S, Omori E, Endo Y, Tamaki N, Morita M, Morita K - PLoS ONE (2013)

Gene expression of inflammatory mediators in the lungs after hemorrhagic shock and resuscitation (HSR).Lungs from the HSR group rats treated with vehicle or biliverdin (BV) were excised at 3 h after resuscitation and the levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) mRNA were determined by Northern blot analysis. (Left) The autoradiographic signals of RNA blot hybridized with [α-32P] deoxycytidine triphosphate-labeled TNF-α (A) or iNOS (B) cDNA. (Right) Concentrations of TNF-α and iNOS mRNA were expressed as arbitrary units. Data are presented as means ± standard deviation and were statistically evaluated using analysis of variance followed by Tukey–Kramer honestly significant difference test (n = 3 per group). *p<0.05 vs. vehicle/sham; †p<0.05 vs. BV/sham; #p<0.05 vs. vehicle/HSR. Vehicle/sham, vehicle-administered animals subjected to sham surgery; BV/Sham, BV-administered animals subjected to sham surgery; vehicle/HSR, vehicle-administered animals subjected to HSR; BV/HSR, BV-administered animals subjected to HSR.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646791&req=5

pone-0063606-g004: Gene expression of inflammatory mediators in the lungs after hemorrhagic shock and resuscitation (HSR).Lungs from the HSR group rats treated with vehicle or biliverdin (BV) were excised at 3 h after resuscitation and the levels of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) mRNA were determined by Northern blot analysis. (Left) The autoradiographic signals of RNA blot hybridized with [α-32P] deoxycytidine triphosphate-labeled TNF-α (A) or iNOS (B) cDNA. (Right) Concentrations of TNF-α and iNOS mRNA were expressed as arbitrary units. Data are presented as means ± standard deviation and were statistically evaluated using analysis of variance followed by Tukey–Kramer honestly significant difference test (n = 3 per group). *p<0.05 vs. vehicle/sham; †p<0.05 vs. BV/sham; #p<0.05 vs. vehicle/HSR. Vehicle/sham, vehicle-administered animals subjected to sham surgery; BV/Sham, BV-administered animals subjected to sham surgery; vehicle/HSR, vehicle-administered animals subjected to HSR; BV/HSR, BV-administered animals subjected to HSR.
Mentions: To elucidate the molecular mechanism underlying the anti-inflammatory effects of BV, we examined the effects of BV treatment on the gene expression of the inflammatory mediators such as TNF-α and iNOS using Northern blot analysis. Although mRNA levels of TNF-α and iNOS were barely detectable in the sham groups irrespective of the presence or absence of BV, these genes were significantly upregulated in the vehicle/HSR group 3 h after resuscitation (Fig. 4). The mRNA levels of TNF-α and iNOS were significantly decreased in the BV/HSR group compared with those in the vehicle/HSR group (Fig. 4).

Bottom Line: Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects.Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs.Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

ABSTRACT
Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-α and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

Show MeSH
Related in: MedlinePlus