Hepatotoxicity of Cardiovascular and Antidiabetic Drugs

Marzio, Dina Halegoua-De; Navarro, Victor J.

doi:10.1016/b978-0-12-387817-5.00029-7

Cited by 25 publications

(29 citation statements)

References 302 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While beta-adrenergic antagonists, particularly labetalol, have been linked to hepatotoxicity, our patient began her beta-blocker months before without incident. 12 Weinstein et al reported a case of hepatotoxicity from Slimquick™ in a woman with the alpha-1-antitrypsin MZ phenotype, suggesting that in seemingly healthy patients, phenotypic variations may explain their predisposition to hepatic injury with drug or supplement ingestion. 1 No studies yet exist that correlate the MS phenotype, which our patient had, with increased risk of liver injury.…”

Section: Discussionmentioning

confidence: 99%

SlimQuickTM-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

Whitsett¹,

Marzio²,

Rossi³

2014

ACG Case Reports Journal

View full text Add to dashboard Cite

Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuick™ (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract.

show abstract

Section: Discussionmentioning

confidence: 99%

SlimQuickTM-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

Whitsett¹,

Marzio²,

Rossi³

2014

ACG Case Reports Journal

View full text Add to dashboard Cite

show abstract

“…Statins have not been shown to cause increased rates of liver injury in patients with abnormal baseline LFTs or chronic liver disease and are considered safe for use with stable liver disease. 1 , 2 , 14 However, the patient’s elevated ALP and total bilirubin suggest active inflammation sufficient to affect the biliary system. Regardless of whether the patient had underlying liver disease, this case therefore is most consistent with acute liver injury related to atorvastatin use that would have remained undetected without routine testing or until the onset of symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…Pioglitazone is also not known to interact with CYP3A4, which metabolizes atorvastatin, reducing the likelihood that this combination resulted in hepatocellular injury as opposed to atorvastatin alone. 2 …”

Section: Discussionmentioning

confidence: 99%

“… 1 Additionally, the Food and Drug Administration no longer recommends routine monitoring of LFTs with statins, as prior efficacy trials have demonstrated no benefit in preventing clinically significant liver injury. 2 We report a case of high-intensity atorvastatin therapy resulting in severe, asymptomatic liver injury, which was recognized only due to routine LFTs.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Severe Liver Injury Associated With High-Dose Atorvastatin Therapy

Saha

Garg

2021

Journal of Investigative Medicine High Impact Case Reports

View full text Add to dashboard Cite

Statins are recommended for first-line management of elevated cholesterol in the primary and secondary prevention of atherosclerotic cardiovascular disease. Statins may occasionally be associated with mild transaminase elevations but can also result in life-threatening liver injury. Atorvastatin is the most common cause of clinically significant liver injury in this drug class. We report a case of severe, asymptomatic liver injury in a hepatocellular pattern in a 71-year-old man occurring within 3 months of switching from simvastatin to high-intensity atorvastatin therapy. Hepatitis improved rapidly with cessation of atorvastatin and did not recur after resuming simvastatin.

show abstract

“…Similarly, high levels of oxidative stress ( Saeidnia and Abdollahi, 2013 ) and compromised liver function or dysfunction of diabetic patients resulted in increased susceptibility to liver toxicity of anti-diabetic drugs ( Chitturi and George, 2001 ; Elserag et al ., 2004 ; Gupte et al ., 2004 ). Exemplifying this, some anti-diabetic drugs such as troglitazone, metformin and TAK-875 showed concern for drug-induced hepatotoxicity, which has resulted in warning, termination of clinical trials and withdrawal from the market ( Gitlin et al ., 1998 ; Halegoua-De Marzio and Navarro, 2013 ; Shah et al ., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Fasiglifam (TAK-875), a G Protein-Coupled Receptor 40 (GPR40) Agonist, May Induce Hepatotoxicity through Reactive Oxygen Species Generation in a GPR40-Dependent Manner

Kim

Koh

et al. 2018

Biomolecules & Therapeutics

View full text Add to dashboard Cite

Fasiglifam (TAK-875) a G-protein coupled receptor 40 (GPR40) agonist, significantly improves hyperglycemia without hypoglycemia and weight gain, the major side effects of conventional anti-diabetics. Unfortunately, during multi-center Phase 3 clinical trials, unexpected liver toxicity resulted in premature termination of its development. Here, we investigated whether TAK-875 directly inflicts toxicity on hepatocytes and explored its underlying mechanism of toxicity. TAK-875 decreased viability of 2D and 3D cultures of HepG2, a human hepatocarcinoma cell line, in concentration- (>50 μM) and time-dependent manners, both of which corresponded with ROS generation. An antioxidant, N-acetylcysteine, attenuated TAK-875-mediated hepatotoxicity, which confirmed the role of ROS generation. Of note, knockdown of GPR40 using siRNA abolished the hepatotoxicity of TAK-875 and attenuated ROS generation. In contrast, TAK-875 induced no cytotoxicity in fibroblasts up to 500 μM. Supporting the hepatotoxic potential of TAK-875, exposure to TAK-875 resulted in increased mortality of zebrafish larvae at 25 μM. Histopathological examination of zebrafish exposed to TAK-875 revealed severe hepatotoxicity as manifested by degenerated hypertrophic hepatocytes with cytoplasmic vacuolation and acentric nuclei, confirming that TAK-875 may induce direct hepatotoxicity and that ROS generation may be involved in a GPR40-dependent manner.

show abstract

Hepatotoxicity of Cardiovascular and Antidiabetic Drugs

Cited by 25 publications

References 302 publications

SlimQuickTM-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

SlimQuickTM-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

Severe Liver Injury Associated With High-Dose Atorvastatin Therapy

Fasiglifam (TAK-875), a G Protein-Coupled Receptor 40 (GPR40) Agonist, May Induce Hepatotoxicity through Reactive Oxygen Species Generation in a GPR40-Dependent Manner

Contact Info

Product

Resources

About