Donepezil‐Induced Hepatotoxicity in an Elderly Adult Taking Fluoxetine

Chew, Aik Phon; Lim, Wee Shiong; Tan, Keng Teng

doi:10.1111/jgs.13023

Cited by 13 publications

(6 citation statements)

References 11 publications

(11 reference statements)

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“…Fluoxetine includes fluorine; if a drug has fluorine in its compound, increase in pharmacokinetic and pharmacodynamic characteristics along with toxic effects appears [ 9 ]. One of the side effects of long-term fluorine drugs is liver injury [ 29 , 30 ]. Fluoxetine is metabolized in the liver by cytochrome p450 and converted into norfluoxetine and several metabolites [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study

Yılmaz

Elbey

Yazgan

et al. 2016

BioMed Research International

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Background. The aim of the study was to analyse the effect of caffeic acid phenethyl ester (CAPE) on fluoxetine-induced hepatotoxicity in rats. Materials and Methods. Group I served as control. Group II received CAPE intraperitoneally. Group III received fluoxetine per orally. Group IV received fluoxetine and CAPE. The total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and liver enzymes including paraoxonase-1 (PON-1), aspartate transaminase, and alanine transaminase levels were measured. Liver tissues were processed histopathologically for evaluation of liver injury and to validate the serum enzyme levels. Results. An increase in TOS and OSI and a decrease in TAC and PON-1 levels in serum and liver tissues of Group III were observed compared to Groups I and II. After treatment with CAPE, the level of TOS and OSI decreased while TAC and PON-1 increased in serum and liver in Group IV. Histopathological examination of the liver revealed hepatic injury after fluoxetine treatment and reduction of injury with CAPE treatment. Conclusion. Our results suggested that CAPE treatment provided protection against fluoxetine toxicity. Following CAPE treatment with fluoxetine-induced hepatotoxicity, TOS and OSI levels decreased, whereas PON-1 and TAC increased in the serum and liver.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study

Yılmaz

Elbey

Yazgan

et al. 2016

BioMed Research International

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“…Previous studies have demonstrated that inhibiting acetylcholinesterase (AChE) might result in liver injury (Uzunhisarcikli and Kalender, 2011;Uzun and Kalender, 2013). Don-induced hepatotoxicity also has been reported in an elderly adult taking fluoxetine (Chew et al, 2014). Furthermore, it has been proven that the cholinergic system plays an important role in Hup A-induced abnormal transaminase activity enhancement (Ma et al, 2003b).…”

Section: Introductionmentioning

confidence: 98%

Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation

Zhang

Sun

et al. 2016

J Pharmacol Exp Ther

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Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic a7 nicotine acetylcholine receptor (a7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and a7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.

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“…As an example, tacrine treatment for Al zheimer disease that was approved by the US Food and Drug Administration in 1993 was discontinued owing to the hepato toxicity seen in about 30%-50% of the treated patients. 39 Very recently, Chew and colleagues 40 showed that donepezil was able to induce hepatotoxicity. Toxicity studies of ASS234 along with donepezil and tacrine were performed in parallel in the human cell line HepG2.…”

Section: In Vitro Experimentsmentioning

confidence: 99%

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

Serrano

Herrero-Labrador

Futch

et al. 2017

JPN

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Donepezil‐Induced Hepatotoxicity in an Elderly Adult Taking Fluoxetine

Cited by 13 publications

References 11 publications

Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study

Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study

Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease

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