Protection by Pentoxifylline Against Normothermic Liver Ischemia/Reperfusion in Rats

Peng, Xing-Xi; Currin, Robert T.; Thurman, Ronald G.; Lemasters, John J.

doi:10.1097/00007890-199506000-00006

Cited by 51 publications

(34 citation statements)

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“…Thus, in experimental studies which examined the effect of PTX on hepatic I/R injury, PTX was administered 1 or 2 h before the operative procedure in order to achieve therapeutic levels of PTX at the beginning of the operation [7,8,18]. In rats that received PTX 1 or 2 h before surgery as a single dose of 50 mg/kg, which is roughly considered equivalent to the maximal dose administered to humans, PTX pretreatment caused a significant decrease of ALT and AST levels for 3-5 h after reperfusion.…”

Section: Figmentioning

confidence: 99%

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Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury

Aslan

Karagüzel²,

Çelik³

et al. 2001

Eur Surg Res

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Aim: Considerable efforts have been made to find and/or eliminate the underyling causes of hepatic ischemia-reperfusion injury, but many points are still unclear. Pentoxifylline-related cytoprotection is one of these unclear points. Our study tests the effects of pentoxifylline on the hepatic cytoprotective process in an experimental model. Materials and Methods: The animals were divided into two groups: (1) placebo-pretreated rats and (2) pentoxifylline-pretreated rats. After pretreatment, all rats underwent the hepatic ischemia-reperfusion procedure which was performed by clamping the hepatoduodenal ligament. To evaluate the liver injury, serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and liver tissue levels of prostaglandin E₂ (PGE₂) were measured before ischemia, immediately after ischemia and immediately after reperfusion. Results: Before ischemia and immediately after ischemia, there were no significant differences between ALT and AST levels of groups 1 and 2 (p >0.05). However, at the end of reperfusion, ALT and AST levels of group 2 were significantly decreased when compared with group 1 (p < 0.05 and p < 0.01, respectively). Additionally, tissue levels of PGE₂ that were obtained before ischemia, immediately after ischemia and immediately after reperfusion in group 2 were significantly higher than those of group 1 (p < 0.001). Conclusion: Pentoxifylline reduces reperfusion injury of the liver through significantly decreased transaminase levels, and contributes to hepatic cytoprotection by increasing tissue levels of PGE₂ significantly. These effects reflect the role of tissue PGE₂ in pentoxifylline-related hepatoprotection against ischemia-reperfusion injury of the liver.

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Section: Figmentioning

confidence: 99%

“…Recently, pentoxifylline (PTX) has also been shown to be effective in reversing hepatic damage due to I/R [7,8]. PTX improves microcirculation, suppresses cytokine release by the stimulated Kupffer cells and inhibits leukocyte adhesion [9].…”

Section: Introductionmentioning

confidence: 99%

Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury

Aslan

Karagüzel²,

Çelik³

et al. 2001

Eur Surg Res

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“…The absence of an effective and safe therapy for HCV-infected renal transplants makes reducing immunosuppression the only accepted approach. Moreover, the extrahepatic features of HCV are being increasingly recognized [33];HCV infection in renal allograft recipients has been incriminated as a cause of transplant glomerulopathy [34, 35], de novo membranoproliferative glomerulonephritis (MPGN) with [7] and without [8] cryoglobulinemia as well as de novo membranous nephropathy [9]. Considering that MPGN and transplant glomerulopathy may be indistinguishable by light microscopy [34] and that only electron microscopic examination of glomerular basement membranes, which is not usually performed in allograft biopsies, offers a clear distinction between the two diagnoses, one should bear in mind that some cases of transplant glomerulopathy may in fact be MPGN.…”

Section: Discussionmentioning

confidence: 99%

“…The immunosuppressive regimens used for the prevention of allograft rejection result in increased HCV replication leading to pathological deterioration in 75% of patients and 25% incidence of cirrhosis within 5 years after transplantation [6]. Moreover, extrahepatic complications of HCV infection such as mixed cryoglobulinemia [7], membranoproliferative [8] or membranous nephritis [9] have been reported after renal transplantation resulting in de novo glomerulonephritis, which may lead to non-functioning renal allografts [9]. …”

Section: Introductionmentioning

confidence: 99%

Interferon Therapy in Hemodialysis Patients with Chronic Hepatitis C: Study of Tolerance, Efficacy and Post-Transplantation Course

Mahmoud¹,

Sobh²,

Elhabashi³

et al. 2005

Nephron Clin Pract

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Background: The potential benefit of pre-transplant treatment of chronic hepatitis C on long-term evolution after renal transplantation is not clear. Methods: Fifty successive renal transplant candidates had their sera positive for HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received a standard course of interferon-α_2b (IFN; 3 MU three times weekly after hemodialysis sessions for 6 months). Results: IFN was discontinued in 2 patients (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the treatment group and in none of the control group. Two patients of the IFN group had a virological relapse post-transplantation. Post-transplant follow-up periods were 41.5 ± 15 and 50 ± 16 months for the treated and control groups respectively. Transaminases remained normal in all patients of the IFN group after transplantation. In contrast, biochemical evidence of acute and chronic hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) patients, respectively, of the control group. Logistic regression analysis identified non-receiving IFN before transplantation as a risk factor for post-transplant hepatic dysfunction (odds ratio = 11.7, p = 0.003) and for chronic allograft nephropathy (odds ratio = 11.6, p = 0.02). Conclusions: IFN-treated patients had a significantly better post-transplant hepatic function and significantly lower rates of chronic allograft nephropathy.

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“…The subsequent infiltration of innate immune cells to the liver results in additional TNF-α production, 6-48 hours after reperfusion. Data from experimental models of I/R injury in which TNF-α is blocked or decreased suggest a potential clinical benefit [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase-3 Ameliorates Total Sublethal Hepatic Ischemia/Reperfusion Injury in a Rat Model

Swamy¹

2012

J Transplant Technol

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Orthotopic liver transplantation is the only treatment for end stage liver disease. Recipients outweigh the number of available healthy donor livers, and options for increasing the donor pool have included the use of marginal livers. Transplantation of marginal livers is a known risk factor for the development of primary non-function post-transplant. Although the precise cause of primary non-function is not known, ischemia/reperfusion (I/R) injury has been strongly implicated, and tumor necrosis factor-α (TNF-α) plays a critical role. We utilized a rat I/R model to determine whether treatment with tissue inhibitor of metalloproteinase-3 (TIMP-3) after total sublethal I/R injury improves liver health by preventing the release of active TNF-α. Rats were pre-treated with either TIMP-3 or saline and underwent total warm hepatic ischemia followed by 6, 24, 48 hours or 7 days reperfusion. All rats survived treatment and I/R injury. Serum samples were assayed for TNF-α, interleukin-6 (IL-6), and alanine aminotransferase (ALT). Histology and RT-PCR for TNF-α and TNF-α-converting enzyme [TACE or a disintegrin and metalloproteinase-17 (ADAM-17)] were performed on liver tissues. TIMP-3 treatment resulted in decreased TNF-α and IL-6 levels, and the inhibition occurred at a posttranscriptional level as mRNA expression of TNF-α and TACE/ADAM-17 was not affected. ALT levels reached basal levels in TIMP-3-treated rats more quickly than untreated rats, and livers of treated rats showed mild edema while livers of untreated rats exhibited hepatic collapse, necrosis, and hemorrhage. Our results indicate that TIMP-3 treatment protects the liver from total sublethal I/R injury through a TNF-α-specific pathway.

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Protection by Pentoxifylline Against Normothermic Liver Ischemia/Reperfusion in Rats

Cited by 51 publications

References 0 publications

Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury

Pentoxifylline Contributes to the Hepatic Cytoprotective Process in Rats Undergoing Hepatic Ischemia and Reperfusion Injury

Interferon Therapy in Hemodialysis Patients with Chronic Hepatitis C: Study of Tolerance, Efficacy and Post-Transplantation Course

Tissue Inhibitor of Metalloproteinase-3 Ameliorates Total Sublethal Hepatic Ischemia/Reperfusion Injury in a Rat Model

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