Mechanism of drug-induced liver injury and hepatoprotective effects of natural drugs

AbstractDrug-induced liver injury (DILI) is a common adverse drug reaction (ADR) and a serious threat to health that affects disease treatments. At present, no targeted clinical drugs are available for DILI. Traditional natural medicines have been widely used as health products. Some natural medicines exert specific hepatoprotective effects, with few side effects and significant clinical efficacy. Thus, natural medicines may be a promising direction for DILI treatment. In this review, we summarize the current knowledge, common drugs and mechanisms of DILI, as well as the clinical trials of natural drugs and their bioactive components in anticipation of the future development of potential hepatoprotective drugs.

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Antioxidant and hepatoprotective effects of Garcinia indica fruit rind in antitubercular drug-induced liver injury in rats

Botanics Targets and Therapy ◽

10.2147/btat.s42483 ◽

2013 ◽

pp. 29

Author(s):

Vandana Panda ◽

Hardik Ashar ◽

Anit Sharan

Keyword(s):

Liver Injury ◽

Antitubercular Drug ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Garcinia Indica ◽

Hepatoprotective Effects ◽

Fruit Rind

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Drug induced hepatitis mimicking Wilson’s disease secondary to the use of complex naturopathic regimens: a case report

BMC Gastroenterology ◽

10.1186/s12876-019-1122-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Tyler Pitre ◽

Jasmine Mah ◽

Jaclyn Vertes ◽

Rosario Rebello ◽

Julie Zhu

Keyword(s):

Liver Injury ◽

Acute Hepatitis ◽

Wilson’S Disease ◽

Factor V Leiden ◽

Wilson's Disease ◽

Natural Health Products ◽

Natural Health ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Health Products

Abstract Background Drug induced liver injury (DILI) is an important cause of acute liver injury and accounts for approximately 10% of all cases of acute hepatitis. Both prescription and natural health products (NHPs) have been implicated in DILI. There is a dearth of studies on NHPs induced liver injury. Case Presentation A previously healthy 37-year-old female presented with subacute hepatitis, in the context of a previous admission to a separate institution, months prior for undiagnosed acute hepatitis. Importantly, she had disclosed taking complex regiments of natural health products (NHPs) for months. Her only other medication was rivaroxaban for her homozygous Factor V Leiden deficiency. She had an extensive work up for causes of acute and unresolving hepatitis. She discontinued several but not all of her NHPs after her initial presentation for acute hepatitis at the first institution and continued taking NHPs until shortly after admission to our institution. The predominant pathological features were that of drug induced liver injury, although an abnormal amount of copper was noted in the core liver biopsies. However, Wilson’s disease was ruled out with normal serum ceruloplasmin and 24-urine copper. After 2 months of stopping all the NHPs, our patient improved significantly since discharge, although there is evidence of fibrosis on ultrasound at last available follow up. Conclusion NHPs are a well-established but poorly understood etiology of DILI. The situation is exacerbated by the unregulated and unpredictable nature of many of the potential hepatotoxic effects of these agents, especially in cases of multiple potential toxic agents. This highlights the importance of acquiring a clear history of all medications regardless of prescription status.

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Models of Idiosyncratic Drug-Induced Liver Injury

The Annual Review of Pharmacology and Toxicology ◽

10.1146/annurev-pharmtox-030220-015007 ◽

2021 ◽

Vol 61 (1) ◽

pp. 247-268 ◽

Cited By ~ 1

Author(s):

Tsuyoshi Yokoi ◽

Shingo Oda

Keyword(s):

Animal Models ◽

Liver Injury ◽

Complex Nature ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Severe Liver Damage ◽

A Cell ◽

Potential Risks ◽

Clinical Drugs ◽

Low Incidence

Drug-induced liver injury (DILI) is a leading cause of attrition during the early and late stages of drug development and after a drug is marketed. DILI is generally classified as either intrinsic or idiosyncratic. Intrinsic DILI is dose dependent and predictable (e.g., acetaminophen toxicity). However, predicting the occurrence of idiosyncratic DILI, which has a very low incidence and is associated with severe liver damage, is difficult because of its complex nature and the poor understanding of its mechanism. Considering drug metabolism and pharmacokinetics, we established experimental animal models of DILI for 14 clinical drugs that cause idiosyncratic DILI in humans, which is characterized by the formation of reactive metabolites and the involvement of both innate and adaptive immunity. On the basis of the biomarker data obtained from the animal models, we developed a cell-based assay system that predicts the potential risks of drugs for inducing DILI. These findings increase our understanding of the mechanisms of DILI and may help predict and prevent idiosyncratic DILI due to certain drugs.

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Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury

Redox Biology ◽

10.1016/j.redox.2015.01.013 ◽

2015 ◽

Vol 4 ◽

pp. 308-320 ◽

Cited By ~ 15

Author(s):

Cheau Yih Tan ◽

Tzuen Yih Saw ◽

Chee Wai Fong ◽

Han Kiat Ho

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Hepatoprotective Effects

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Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽

10.1024/1661-8157/a000298 ◽

2010 ◽

Vol 99 (21) ◽

pp. 1259-1265 ◽

Cited By ~ 2

Author(s):

Bruggisser ◽

Terraciano ◽

Rätz Bravo ◽

Haschke

Keyword(s):

Liver Injury ◽

Wird Eine ◽

Drug Induced ◽

Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

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