Naproxen-induced oxidative stress in the isolated perfused rat liver

Background: Heavy water (D2O) has many biological effects due to the isotope effect of deuterium. We previously reported the efficacy of D2O containing solution (Dsol) in the cold preservation of rat hearts. Here, we evaluated whether Dsol reduced hepatic cold preservation and reperfusion injury. Methods: Rat livers were subjected to 48-hour cold storage in University of Wisconsin (UW) solution or Dsol, and subsequently reperfused on an isolated perfused rat liver. Graft function, injury, perfusion kinetics, oxidative stress, and cytoskeletal integrity were assessed. Results: In the UW group, severe ischemia and reperfusion injury (IRI) was shown by histopathology, higher liver enzymes leakage, portal resistance, and apoptotic index, oxygen consumption, less bile production, energy charge, and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio (versus control). The Dsol group showed that these injuries were significantly ameliorated (versus the UW group). Furthermore, cytoskeletal derangement was progressed in the UW group, as shown by less degradation of α-Fodrin and by the inactivation of the actin depolymerization pathway, whereas these changes were significantly suppressed in the Dsol group. Conclusion: Dsol reduced hepatic IRI after extended cold preservation and subsequent reperfusion. The protection was primarily due to the maintenance of mitochondrial function, cytoskeletal integrity, leading to limiting oxidative stress, apoptosis, and necrosis pathways.

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Mitigation of nitrofurantoin-induced toxicity in the perfused rat liver

Human & Experimental Toxicology ◽

10.1177/096032719601500511 ◽

1996 ◽

Vol 15 (5) ◽

pp. 428-434 ◽

Cited By ~ 7

Author(s):

Wei Shen ◽

Betty-ann Hoener

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Rat Liver ◽

Radical Anion ◽

Treatment Strategies ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Tetraacetic Acid ◽

Protein Thiols ◽

Futile Cycling

1 Nitrofurantoin is an antimicrobial agent which pro duces hepatotoxicity caused by the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress. 2 Our goal was to determine treatment strategies which could mitigate nitrofurantoin-induced toxicity in the isolated perfused rat liver. We co-infused various agents which blocked early or late events in the progression to toxicity. Tissue levels of glutathione and protein thiols were measured as indicators of the progression to toxicity and lactate dehydrogenase leakage into the perfusate was used as a marker of irreversible cell death. 3 Five treatments significantly ( P < 0.05) decreased LDH leakage (reported as thousands of units accumulated in perfusate at 300 min, mean ± standard error, n=3- 4) when compared to nitrofurantoin alone (274 ±37). These treatments were adenosine-2'-monophosphate (120 ± 53), penicillamine (90 ± 29), N-(2-mercaptopro pionyl)-glycine (120 ± 49) and bromosulfophthalein with (80 ± 29) or without 5,5'-difluro-1,2-bis(O-amino phenoxy)ethane-N,N,N'N'-tetraacetic acid (101 ± 46). Two other treatments, N-acetylcysteine (183 ± 7) and dithiothreitol (166 ± 59) delayed the onset of toxicity. Finally, calpeptin (319 ± 34) which blocks activation of nonlysosomal proteases was ineffective. 4 We concluded that early intervention on the pathway to toxicity was most effective. The strategies detailed here may prove beneficial in treating hepatotoxicity seen following nitrofurantoin therapy.

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Nitrofurazone: Kinetics and oxidative stress in the singlepass isolated perfused rat liver

Biochemical Pharmacology ◽

10.1016/0006-2952(88)90028-7 ◽

1988 ◽

Vol 37 (8) ◽

pp. 1629-1636 ◽

Cited By ~ 11

Author(s):

Betty-Ann Hoener

Keyword(s):

Oxidative Stress ◽

Rat Liver ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

And Oxidative Stress

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Acetaminophen-induced liver oxidative stress and hepatotoxicity: influence of Kupffer cell activity assessed in the isolated perfused rat liver

Redox Report ◽

10.1080/13510002.1997.11747112 ◽

1997 ◽

Vol 3 (4) ◽

pp. 213-218 ◽

Cited By ~ 6

Author(s):

G. Tapia ◽

P. Cornejo ◽

J. Ferreira ◽

V. Fernández ◽

L. A. Videla

Keyword(s):

Oxidative Stress ◽

Rat Liver ◽

Kupffer Cell ◽

Cell Activity ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver

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Lindane-induced liver oxidative stress: Respiratory alterations and the effect of desferrioxamine in the isolated perfused rat liver

Cell Biochemistry and Function ◽

10.1002/cbf.290070305 ◽

1989 ◽

Vol 7 (3) ◽

pp. 179-183 ◽

Cited By ~ 10

Author(s):

Luis A. Videla ◽

Kiyoko Simizu ◽

SilVia B. M. Barros ◽

Virginia B. C. Junqueira

Keyword(s):

Oxidative Stress ◽

Rat Liver ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver

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A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657155 ◽

1982 ◽

Vol 47 (02) ◽

pp. 166-172 ◽

Cited By ~ 4

Author(s):

Yoav Sharoni ◽

Maria C Topal ◽

Patricia R Tuttle ◽

Henry Berger

Keyword(s):

Rat Liver ◽

Isoelectric Point ◽

Rat Hepatocytes ◽

Cell Types ◽

Plasminogen Activators ◽

Rat Plasma ◽

Isolated Perfused Rat Liver ◽

Perfused Rat Liver ◽

Molecular Weights ◽

Physiological Relevance

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

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