Enoxaparin prevents fibrin accumulation in liver tissues and attenuates methotrexate-induced liver injury in rats

Ewees, Mohamed G; Abdelghany, Tamer M.; Abdelaziz, Abdelaziz H.; Abdel-Bakky, Mohamed Sadek

doi:10.1007/s00210-019-01618-1

Cited by 3 publications

(1 citation statement)

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“…Hepatocellular injury is the most common adverse effect of high-dose MTX, with hepatocellular damage localised in liver sinusoidal endothelial cells (Sotoudehmanesh et al 2010). High-dose MTX in vivo significantly elevates ALT and AST levels, increases expression of fibrin and, leads to severe steatosis, sinusoidal dilation, as well as, moderate inflammation and necrosis (Ewees et al 2019). Given the clinical nature of MTX and strong, reproducible evidence MTX induces severe hepatocellular injury in vivo, MTX may be favoured over traditional APAP and CCl 4 in vivo rat models of DILI.…”

Section: M30mentioning

confidence: 99%

The application of cytokeratin-18 as a biomarker for drug-induced liver injury

et al. 2021

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Drug-induced liver injury (DILI) is a frequent and dangerous adverse effect faced during preclinical and clinical drug therapy. DILI is a leading cause of candidate drug attrition, withdrawal and in clinic, is the primary cause of acute liver failure. Traditional diagnostic markers for DILI include alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Yet, these routinely used diagnostic markers have several noteworthy limitations, restricting their sensitivity, specificity and accuracy in diagnosing DILI. Consequently, new biomarkers for DILI need to be identified.A potential biomarker for DILI is cytokeratin-18 (CK18), an intermediate filament protein highly abundant in hepatocytes and cholangiocytes. Extensively researched in a variety of clinical settings, both full length and cleaved forms of CK18 can diagnose early-stage DILI and provide insight into the mechanism of hepatocellular injury compared to traditionally used diagnostic markers. However, relatively little research has been conducted on CK18 in preclinical models of DILI. In particular, CK18 and its relationship with DILI is yet to be characterised in an in vivo rat model. Such characterization of CK18 and ccCK18 responses may enable their use as translational biomarkers for hepatotoxicity and facilitate management of clinical DILI risk in drug development. The aim of this review is to discuss the application of CK18 as a biomarker for DILI. Specifically, this review will highlight the properties of CK18, summarise clinical research that utilised CK18 to diagnose DILI and examine the current challenges preventing the characterisation of CK18 in an in vivo rat model of DILI.

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Section: M30mentioning

confidence: 99%