Role of Bilirubin as an Antioxidant in an Ischemia–Reperfusion of Rat Liver and Induction of Heme Oxygenase

Yamaguchi, Tokio; Terakado, Masaaki; Horio, Fumihiko; Aoki, Kazuma; Tanaka, Makiko; Nakajima, Hiroshi

doi:10.1006/bbrc.1996.0857

Cited by 151 publications

(90 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32 As for the association of HO-1/HSP32, bilirubin generated by HO-1/HSP32 is reported to provide antioxidative properties in the liver. 33 Furthermore, HO-derived CO may contribute to the maintenance of hepatic sinusoidal vascular tone not only in a perfusion model of the rat liver, 16 but also in an in vivo hemorrhage/ resuscitation model. 34 In these studies, zinc protoporphyrin-IX, a potent inhibitor of HO, was shown to increase portal vascular resistance.…”

Section: Resultsmentioning

confidence: 99%

Impact of hyperthermic preconditioning on postischemic hepatic microcirculatory disturbances in an isolated perfusion model of the rat liver

et al. 2000

View full text Add to dashboard Cite

Sublethal hyperthermia and the following recovery from this heat exposure, referred to as hyperthermic preconditioning, elicits a transient state of tolerance to oxidative insults through an intracellular protective response: stress response. The impact of hyperthermic preconditioning on hepatic microcirculatory disturbance, which is one of the determinants of ischemia/reperfusion-induced injury of the liver, was investigated by using intravital fluorescence microscopy. Thirty minutes of ischemia and a subsequent 120 minutes of reperfusion was induced in an in situ isolated perfusion model of Sprague-Dawley rats. Heat stress was given by whole-body hyperthermia, and a subsequent recovery was allowed for 18 or 48 hours, respectively. Postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, leukocyte stagnation in sinusoids, and leukocyte adhesion in postsinusoidal venules were significantly attenuated in both hyperthermia-pretreated groups. A recovery of bile production, a reduction of liver enzyme release, and an attenuation of tissue edema and histological damage were also observed. A marked expression of heat shock protein (HSP) 70 and heme oxygenase (HO-1)/HSP32 was correlatively observed in the liver tissue coincident with the induction of these protective effects. Hyperthermic preconditioning provides a continuous long-term and constant inhibitory effect (up to 48 hours after heat exposure) on postischemic injury of the liver through the attenuation of microcirculatory disturbances. These beneficial effects might be associated with a concomitant increase in HSP70 and HO-1/HSP32 expression. (HEPATOLOGY 2000;31:407-415.)Ischemia/reperfusion-induced injury is one of the major perioperative complications in liver surgery and liver transplantation. The administration of specific protective agents has been attempted to reduce postischemic hepatic injury. [1][2][3] To the contrary, preconditioning therapies based on an endogenous protection response against stressful events, referred to as heat stress response, have been studied as another therapeutic strategy. Hyperthermic preconditioning, the exposure to a transient sublethal hyperthermia, and the following appropriate recovery develops protection not only to subsequent thermal stress, but also to oxidative stress such as ischemia/reperfusion. [4][5][6][7][8] Heat stress response has been reported to be associated with the induction of specific heat shock proteins (HSPs). In particular, HSP70 is generally considered to contribute to the protective mechanism of hyperthermic preconditioning, based on the finding that overexpression of HSP70 in a transgenic mouse increases the resistance of the heart to ischemic injury. 9,10 Heme oxygenase (HO)-1/HSP32 is another HSP playing a role in the modulation of the inflammatory response. HO catabolizes intracellular heme to biliverdin, which is converted to bilirubin by bilirubin reductase. During this degradation process, carbon monoxide (CO) is released. 11 HO consists of HO-1 (inducible isoenzyme) and ...

show abstract

Section: Resultsmentioning

confidence: 99%

Impact of hyperthermic preconditioning on postischemic hepatic microcirculatory disturbances in an isolated perfusion model of the rat liver

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In addition, the classical pathway for ethanol metabolism in liver appears to be associated with the formation of free radicals 41) . Since free radicals induction might reflect induction of heme oxygenase, an enzyme of bilirubin biosynthesis in the liver 42) , biopyrrins probably increased, as a result of oxidation of bilirubin synthesized in the liver. Accordingly, the total biopyrrin level might directly reflect oxidative stress produced in the liver and correlate well with increase in the levels of GOT, GPT, and γ-GTP.…”

Section: Discussionmentioning

confidence: 99%

Moderate Alcohol Consumption Reduces Urinary 8-Hydroxydeoxyguanosine by Inducing of Uric Acid.

Yoshida

Shioji²,

Kishida

et al. 2001

INDUSTRIAL HEALTH

View full text Add to dashboard Cite

Recent studies suggest that moderate alcohol consumption is associated with a low risk of cancer, coronary heart disease, and other diseases. Most of these diseases are considered to be related to the action of reactive oxygen species (ROS) at certain stages of disease progression. However, considerable evidence exists indicating that ethanol generates ROS in vivo. Thus, the reduced risk of disease as a result of alcohol consumption seems to contradict evidence suggesting the induction of ROS by ethanol. In the present study, we investigated whether oxidative stress was induced in moderate alcohol drinkers. We measured the total urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG) levels as a systemic oxidative stress marker and an oxidative DNA damage marker, respectively. Serum uric acid was also measured as an alcohol-induced antioxidant. We compared total urinary biopyrrins and 8-OHdG levels among groups with different alcohol habits. The results showed that total biopyrrins levels increased with the amount of alcohol consumed, but that the level of 8-OHdG significantly decreased with the amount of alcohol consumed. The decrease in 8-OHdG levels seemed to be associated with increasing levels of uric acid. Judging from the increasing level of total biopyrrins, alcohol may induce ROS. ROS may then cause cell damage in liver, as suggested by the positive correlation between the total biopyrrins levels and the serum GOT, GPT, and γ γ γ γ γ-GTP levels. However, since ROS may be more effectively counteracted by uric acid in organs other than the liver, DNA damage may be surpressed rather than induced. Accordingly, moderate alcohol consumption seems to have the overall effect of reducing DNA damage, as shown by the decrease in urinary 8-OHdG levels observed in our study.

show abstract

“…Biopyrrins are oxidative metabolites of bilirubin and are generated under stress conditions such as poor mental health, infection, ischemia, and surgery (11,24,25). We have focused on the biopyrrin level in the clinical setting because it involves noninvasive sampling and reflects lifestyle factors such as psychological status (11).…”

Section: Participantsmentioning

confidence: 99%

Effects of lifestyle factors on urinary oxidative stress and serum antioxidant markers in pregnant Japanese women: A cohort study

Matsuzaki

Haruna

Ota

et al. 2014

BST

Self Cite

View full text Add to dashboard Cite

Role of Bilirubin as an Antioxidant in an Ischemia–Reperfusion of Rat Liver and Induction of Heme Oxygenase

Cited by 151 publications

References 0 publications

Impact of hyperthermic preconditioning on postischemic hepatic microcirculatory disturbances in an isolated perfusion model of the rat liver

Impact of hyperthermic preconditioning on postischemic hepatic microcirculatory disturbances in an isolated perfusion model of the rat liver

Moderate Alcohol Consumption Reduces Urinary 8-Hydroxydeoxyguanosine by Inducing of Uric Acid.

Effects of lifestyle factors on urinary oxidative stress and serum antioxidant markers in pregnant Japanese women: A cohort study

Contact Info

Product

Resources

About