The regulation of pyrimidine nucleotide level and its role in experimental Hepatitis

Decker, Karl; Keppler, Dietrich; Pausch, Jürgen

doi:10.1016/0065-2571(73)90017-4

Cited by 55 publications

(21 citation statements)

References 49 publications

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“…d-GalN causes hepatic injury with spotty necrosis of hepatic parenchyma and marked portal and parenchymal infiltration (Keppler & Decker, 1969). d-GalN also causes depletion of uridine diphosphate (UDP) by increasing the formation of UDP-sugar derivatives, which results in inhibition of RNA and protein synthesis leading to cell membrane deterioration (Decker et al, 1973;EI-Mofty et al, 1975). Javle et al (1998) reported that d-GalN-induced liver injury is associated with alteration in renal hemodynamics thus altering its function.…”

Section: Discussionmentioning

confidence: 99%

Brassica nigraplays a remedy role in hepatic and renal damage

Rajamurugan¹,

Arumugam²,

Selvaganabathy³

et al. 2012

Pharmaceutical Biology

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Section: Discussionmentioning

confidence: 99%

Brassica nigraplays a remedy role in hepatic and renal damage

Rajamurugan¹,

Arumugam²,

Selvaganabathy³

et al. 2012

Pharmaceutical Biology

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“…The toxicity of GalN results from a dose dependent depletion of uridine nucleotides, which causes inhibition of RNA synthesis and disturbance in the biosynthesis of glycoproteins [4] leading to deterioration of cell membranes and associated increases in the intracellular concentration of calcium ions [5,6]. These changes suggest that an endogenous Ca 2+ -dependent endonuclease activity, triggered by an increase in nuclear Ca 2+ concentration, may be responsible for DNA fragmentation during apoptosis and for certain types of toxic cell death.…”

Section: Introductionmentioning

confidence: 99%

D-Galactosamine Induced Hepatocyte Apoptosis is Inhibited in vivo and in Cell Culture by a Calcium Calmodulin Antagonist, Chlorpromazine, and a Calcium Channel Blocker, Verapamil.

et al. 2003

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Studies were conducted in C57BL/6N Crj male mice and in cultured hepatocytes to clarify the relationship between galactosamine (GalN) induced apoptosis and [Ca 2+ ]i kinetics. Chlorpromazine (CPZ), a Ca 2+ -calmodulin antagonist, and verapamil (VR), a Ca 2+ -channel blocker each inhibited GalN-induced DNA fragmentation and the appearance of apoptotic bodies. The kinetics of calcium uptake were evaluated using a calcium analyzer with the acetoxymethyl ester of fura-PE3 (fura-PE3/AM, 2.5 µM) as the calcium reporter. An increase in [Ca 2+ ]i was detected in the cultured hepatocytes within 3 hours after treatment with 20 mM GalN; this increase was inhibited by pretreatment with either 20 µM CPZ or 30 µM VR. Ca 2+ imaging by confocal laser scanning microscopy showed that increase in [Ca 2+ ]i after treatment with GalN was initially localized around nuclei, while [Ca 2+ ]i signals were later diffuse and observed throughout the cytoplasm. The activities of lactate dehydrogenase (LDH) and serum glutamate-pyruvate transaminase (sGPT), used as indicators of plasma membrane damage and leakage, however, were not reduced by pretreatment with CPZ or VR. From these findings, we infer that the DNA fragmentation in GalN-induced hepatocyte apoptosis is associated with an elevation in the perinuclear concentration of Ca 2+ , but GalN-induced necrotic cell death is triggered through pathway(s) that are insensitive to blockage of Ca 2+ influx and therefore appear to occur independently of elevation in [Ca 2+ ]i. These results help to clarify the role of calcium flux in hepatocyte apoptosis and necrosis induced by exposure to hepatotoxins in vivo and in vitro.

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“…GalN causes liver cell injury, with spotty hepatocyte necrosis and prominent portal and parenchymal inflammation [4]. GalN also causes depletion of uridine diphosphate (UDP) by increasing the formation of UDP-sugar derivatives, which results in inhibition of RNA and protein synthesis, leading to deterioration of the cell membranes [5,6].…”

Section: Introductionmentioning

confidence: 99%

Effects of Bergenin, the Major Constituent of <i>Mallotus japonicus</i> against <i>D</i>-Galactosamine-Induced Hepatotoxicity in Rats

et al. 2001

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The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Bergenin (50, 100 and 200 mg/kg) was given orally once daily for 7 successive days and then GalN 400 mg/kg was injected intraperitoneally to rats at 24 and 96 h after the final administration of bergenin. Pretreatment with bergenin reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, γ-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN towards normalization, suggesting that the hepatoprotective effects of bergenin may consist in maintaining adequate levels of hepatic glutathione for the removal of xenobiotics. The present results indicate that bergenin has hepatoprotective effects against GalN-induced hepatotoxicity in rats.

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The regulation of pyrimidine nucleotide level and its role in experimental Hepatitis

Cited by 55 publications

References 49 publications

Brassica nigraplays a remedy role in hepatic and renal damage

Brassica nigraplays a remedy role in hepatic and renal damage

D-Galactosamine Induced Hepatocyte Apoptosis is Inhibited in vivo and in Cell Culture by a Calcium Calmodulin Antagonist, Chlorpromazine, and a Calcium Channel Blocker, Verapamil.

Effects of Bergenin, the Major Constituent of <i>Mallotus japonicus</i> against <i>D</i>-Galactosamine-Induced Hepatotoxicity in Rats

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