31p Nuclear Magnetic Resonance Study of Phospholipids in Ischemia/Reperfusion Injury in a Rat Fatty Liver Model

Reddy, M. Chandra Sekhar; Koneru, Baburao; Soni, Sunil; Patel, Deepan

doi:10.1097/00007890-199604270-00005

Cited by 11 publications

(4 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Support for this concept is provided by previous observations of decreased liver phospholipids and increased lipid peroxidation products, in rat fatty livers, during reperfusion following warm ischemia. 8,9,34 Further support is provided by the significant increase in survival of animals in antioxidant groups I and III, groups that received additional TOC following reperfusion. TOC protects membranes from free radical attack and, in the process, becomes oxidized to tocopheroxyl radical.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

2001

View full text Add to dashboard Cite

Fatty livers in humans and rats are less tolerant of ischemia, endotoxin, and alcohol. We hypothesized that fatty livers of obese (Ob) Zucker rats are oxidatively stressed and oxidative stress could be relieved by antioxidant treatment, leading to improved tolerance to ischemia. Total glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), and selenium-glutathione peroxidase (Se-GPx) were measured in the livers of Ob and lean (Ln) Zucker rats before and after treatment with high-dose TOC and ascorbate. Also, survival in treated Ob rats following a lethal 90 minutes of partial in vivo warm ischemia was examined. Fatty livers of Ob rats contained significantly less GSH, TOC, and CAT, in comparison with livers of Ln rats. Immunoblotting showed significantly decreased CAT protein without changes in mRNA in fatty livers. There were no significant differences in AA, SOD, and Se-GPx between the 2 groups. Pretreatment with TOC and ascorbate over 48 hours completely corrected the decreases in GSH, TOC, and CAT. Most importantly, TOC with or without ascorbate pretreatment significantly improved survival in Ob rats following ischemia in a dosedependent manner. Fatty livers in humans and experimental animals are more prone to a variety of insults such as ischemia/reperfusion (I/ RP), endotoxin, and alcohol. Nonalcoholic steatohepatitis and its progression to cirrhosis are well-defined clinical entities. 1 Recipients of human donor livers with moderate or severe steatosis have decreased graft and patient survival. 2 Although exact figures are not available, it is believed that as many as 30% of donor livers have varying degrees of steatosis on routine microscopic examination. About 10% of donor livers are not used for transplantation because of moderate to severe steatosis, and this worsens the current shortage of livers. 2 Treatment regimens that will improve tolerance of fatty livers to the aforementioned insults are needed, and would benefit a diverse group of patients.Two rodent models of fatty liver, the genetically obese (Ob) and lipotrope-deficient diet models, are used in the laboratory to further investigate the problems associated with fatty livers. Abnormalities in sinusoidal microcirculation, 3,4 mitochondrial oxidative phosphorylation including a decrease in adenosine triphosphate production, 5,6 and dysregulation of cytokine production 7 are some of the mechanisms that have been associated with the increased injury to fatty livers in both rodents and humans. Oxidative stress has recently been postulated to be a common feature in fatty livers of diverse etiologies. 1 Lipid peroxidation products in the liver are increased in both models of rat fatty liver. 8,9 Reactive oxygen intermediates are key mediators of I/RP injury in solid organs. Thus, a 2-step oxidative injury comprised of a chronic oxidative stress before and an additional acute oxidative stress following I/RP may explain the increased injury sustained by fatty livers following both cold and warm ischemia.To...

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

2001

View full text Add to dashboard Cite

show abstract

“…Steatotic livers substantially contribute to the donor pool, thereby partially compensating for organ shortage. Clinical and experimental studies have shown that steatotic livers are more susceptible to IRI than lean livers [3,4,[22][23][24][25] . This results in increased plasma aminotransferases and diminished liver function in the early postoperative phase following transplantation [3,4] .…”

Section: Discussionmentioning

confidence: 99%

GSH Attenuates Organ Injury and Improves Function after Transplantation of Fatty Livers

et al. 2010

View full text Add to dashboard Cite

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 µmol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation.

show abstract

“…Some activation of intracellular cascade for signal transmission is included and is connected to the final pathway for de novo synthesis of HSP72 [29]. It is known that steatotic liver is more sensitive to harmful stresses than normal liver [4,30]. Fat deposition may possibly change the intracellular environment.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Preconditioning Ameliorates Liver Injury Following Normothermic Ischemia–Reperfusion in Steatotic Rat Livers

Yamagami¹,

Yamamoto²,

Kume³

et al. 1998

Journal of Surgical Research

View full text Add to dashboard Cite

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2-nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.

show abstract

31p Nuclear Magnetic Resonance Study of Phospholipids in Ischemia/Reperfusion Injury in a Rat Fatty Liver Model

Cited by 11 publications

References 22 publications

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol

GSH Attenuates Organ Injury and Improves Function after Transplantation of Fatty Livers

Heat Shock Preconditioning Ameliorates Liver Injury Following Normothermic Ischemia–Reperfusion in Steatotic Rat Livers

Contact Info

Product

Resources

About