Diclofenac induces apoptosis in hepatocytes

Gómez‐Lechón, M. José; Ponsoda, Xavier; O’Connor, Enrique; Donato, M. Teresa; Jover, Ramiro; Castell, José V.

doi:10.1016/s0887-2333(03)00105-x

Cited by 67 publications

(56 citation statements)

References 25 publications

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“…when green tea was associated with diclofenac [12] or paracetamol [11,20], since hepatotoxicity has been reported for these drugs [36][37][38]. Three other patients were also taking progestogens [13,14,33], which has been associated with some cases of toxic hepatitis [39,40].…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Mazzanti

Menniti‐Ippolito²,

Moro

et al. 2009

Eur J Clin Pharmacol

351

251

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Purpose To review the current literature on suspected green tea-related hepatic reactions and to describe two new cases reported within the framework of the Italian surveillance system of natural health products. Results A literature search of publication between 1999 and October 2008 retrieved 34 cases of hepatitis. Histological examination of the liver revealed inflammatory reactions, cholestasis, occasional steatosis, and necrosis. A positive dechallenge was reported in 29 cases. There was one reported death. A positive rechallenge occurred in seven cases (20%). In the two new cases, the causality assessment was judged as "possible" according to the RUCAM score. Conclusions Our analysis of the published case reports suggests a causal association between green tea and liver damage. The hepatotoxicity is probably due to (-)-epigallocatechin gallate or its metabolites which, under particular conditions related to the patient's metabolism, can induce oxidative stress in the liver. In a few cases, toxicity related to concomitant medications could also be involved.

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Section: Discussionmentioning

confidence: 99%

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Mazzanti

Menniti‐Ippolito²,

Moro

et al. 2009

Eur J Clin Pharmacol

351

251

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“…The cells were incubated with DF or MLX in the presence or absence of the uric acid for 6, 8 and 12 h. The cell cultures were thereafter incubated with DCFH-DA, a specific indicator of intracellular ROS formation, for 30 min and washed with HBSS (Gomez- Lechon et al, 2003). The change in absorption was read at on a Varion spectrophotometer at 504 nm (Somogyi et al, 2007).…”

Section: Ros Studiesmentioning

confidence: 99%

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

Naidoo

Swan

2009

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…Apoptosis was observed after exposure to sub-cytotoxic concentrations of diclofenac, mediated by opening the MPT pore and increased ROS, with activation of caspase 3, 8 & 9. These changes were prevented by anti-oxidant treatment, implicating mitochondrial ROS in caspase activation and downstream induction of apoptosis [97, 99]. It was also recently shown that diclofenac treatment decreased mitochondrial membrane potential in both rat and human hepatocytes in vitro, accompanied by mitochondrial fragmentation due to decrease in the mitochondrial fusion protein Mfn1 [104].…”

Section: Diclofenac Hepatotoxicitymentioning

confidence: 99%

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

et al. 2018

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Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. The utilization of circulating mitochondrial-specific biomarkers in understanding mechanisms of toxicity in humans will also be examined. In summary, it is well-established that mitochondria are central to acetaminophen-induced cell death. However, the most promising areas for clinically useful therapeutic interventions after acetaminophen toxicity may involve the promotion of adaptive responses and repair processes including mitophagy and mitochondrial biogenesis, In contrast, the limited understanding of the role of mitochondria in various aspects of hepatotoxicity by most other drugs and herbs requires more detailed mechanistic investigations in both animals and humans. Development of clinically relevant animal models and more translational studies using mechanistic biomarkers are critical for progress in this area.

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Diclofenac induces apoptosis in hepatocytes

Cited by 67 publications

References 25 publications

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Hepatotoxicity from green tea: a review of the literature and two unpublished cases

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives

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