Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease

Cattral, Mark S.; Altraif, Ibraham; Greig, Paul D.; Blendis, Laurence M.; Levy, Gary

doi:10.1016/0002-9343(94)90305-0

Cited by 40 publications

(12 citation statements)

References 29 publications

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“…This in vitro phenomenon seems to be clinically relevant in vivo, in the sense that patients in which this phenomenon was detected had a less severe disease, as assessed by aminotransferase concentrations and more rapid cure. This observation is interesting in view of the data showing a protective role of prostaglandins, namely PGE 2 , in experimental models of liver injury,30 as well as in patients with fulminant hepatic failure 31. Recent studies have shown that PGE 2 profoundly inhibits the synthesis of interleukin 2 and interferon γ,32 33 two lymphokines associated with the Th1 pattern, but not of interleukin 4 and interleukin 10 secreted by Th2 cells.…”

Section: Discussionmentioning

confidence: 83%

Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

Maria

Victorino

1997

Gut

112

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Background-Diagnosis of drug induced liver injury is usually based on a temporal relation between drug intake and clinical picture as well as on the exclusion of alternative causes. More precise diagnosis has been attempted by using in vitro specific T cell reactivity to drugs but the test has never reached general acceptability because of frequent negative results which could be explained, in part, by prostaglandin producing suppressor cells (PPSC). Results-When PBMC were stimulated with drugs alone, lymphocyte sensitisation to drugs (SI>2) was detected in 26% of the cases. This was noticeably increased (56%) when a prostaglandin inhibitor was added to the cultures. No reactivity was found in controls. In patients with possible sensitivity to several drugs, lymphocyte reactivity was detected to only one drug. The severity of the lesions, as assessed by aminotransferase concentrations and disease duration, was lower in patients with evidence of PPSC. Conclusions-This new approach is useful for the diagnosis of drug induced liver injury, particularly in patients exposed to more than one drug; furthermore, the presence of putative PPSC is associated with less severe forms of drug induced hepatitis. (Gut 1997; 41: 534-540) Aim-To

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Section: Discussionmentioning

confidence: 83%

Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

Maria

Victorino

1997

Gut

112

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“…Other treatments such as insulin/glucagon, prostaglandin E2 and corticosteroids (even in fulminant autoimmune hepatitis) have failed to show significant benefit in ALF and are not recommended 82, 109–112 . A recent RCT of l ‐ornithine– l ‐aspartate (LOLA) in ALF patients, predominantly with acute viral hepatitis, found LOLA to be ineffective in reducing either ammonia levels or mortality rates, with a trend towards increased seizure rates in the LOLA arm 113 …”

Section: Specific Therapies In Alfmentioning

confidence: 99%

Review article: the current management of acute liver failure

Craig¹,

Lee

Hayes

et al. 2010

Aliment Pharmacol Ther

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“…PGE 1 analogues have been used in experimental models of ischemia-reperfusion injury and inflammation; in clinical treatments of rheumatoid arthritis, systemic sclerosis, pulmonary hypertension, and glomerulonephritis; in hepatic, renal, and cardiac surgeries; and in neurosurgical procedures, due to their documented anti-inflammatory and cytoprotective actions [28, 30, 31, 33–36]. However, the use of prostaglandins in clinical settings has been limited because of poor oral bioavailability, significant toxicity profiles such as diarrhea, emesis, and hypotension [38, 39], and short half-lives [40, 41]. Misoprostol, which is a structural analogue of naturally occurring PGE 1 , is designed to overcome these problems.…”

Section: Introductionmentioning

confidence: 99%

Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease

Gobejishvili

Ghare

Khan³

et al. 2015

Clinical Immunology

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Dysregulated cytokine metabolism plays a critical role in the pathogenesis of many forms of liver disease, including alcoholic and non-alcoholic liver disease. In this study we examined the efficacy of Misoprostol in modulating LPS-inducible TNFα and IL-10 expression in healthy human subjects and evaluated molecular mechanisms for Misoprostol modulation of cytokines in vitro. Healthy subjects were given 14 day courses of Misoprostol at doses of 100, 200, and 300 µg four times a day, in random order. Baseline and LPS-inducible cytokine levels were examined ex vivo in whole blood at the beginning and the end of the study. Additionally, in vitro studies were performed using primary human PBMCs and the murine macrophage cell line, RAW 264.7, to investigate underlying mechanisms of misoprostol on cytokine production. Administration of Misoprostol reduced LPS inducible TNF production by 29%, while increasing IL-10 production by 79% in human subjects with no significant dose effect on ex vivo cytokine activity; In vitro, the effect of Misoprostol was largely mediated by increased cAMP levels and consequent changes in CRE and NFκB activity, which are critical for regulating IL-10 and TNF expression. Additionally, chromatin immunoprecipitation (ChIP) studies demonstrated that Misoprostol treatment led to changes in transcription factor and RNA Polymerase II binding, resulting in changes in mRNA levels. In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role.

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Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease

Cited by 40 publications

References 29 publications

Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

Review article: the current management of acute liver failure

Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease

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