• Drug-induced liver injury
• Mitochondrial dysfunction
• Omics
• Personalized medicine
• Preclinical models

• ATF3/FSP1 signaling
• Co-administration detoxification
• Co-catalpol
• Ferroptosis
• Fluoxetine-induced hepatotoxicity

• Mice
• Animals
• Fluoxetine/pharmacology
• Activating Transcription Factor 3
• Ferroptosis
• Chemical and Drug Induced Liver Injury, Chronic
• Molecular Docking Simulation
• Prospective Studies
• Antidepressive Agents/pharmacology
• Cyclic AMP Response Element-Binding Protein
• Iridoid Glucosides

• Fisetin
• fluoxetine
• glial fibrillary acidic protein
• inducible nitric oxide synthase
• liver

Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.

To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.

Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.

Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.

These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

• Fluoxetine
• Hepatotoxicity
• Oxidative stress
• Baicalin
• Anti-inflammatory
• Hepatoprotective and antioxidant

• Elabela
• potassium channels
• thoracic aorta
• tissue bath
• vasorelaxation

• Liver damage
• fluoxetine
• nuclear factor erythroid 2-related factor 2 (Nrf2)
• peroxisome proliferator-activated receptor-gamma
• vinpocetine

• Caffeic acid phenethyl ester
• Experimental periodontitis
• Total antioxidant status
• Total oxidant status

• Animals
• Antioxidants/pharmacology
• Caffeic Acids/pharmacology
• Oxidative Stress
• Periodontitis/drug therapy
• Phenylethyl Alcohol/analogs & derivatives
• Phenylethyl Alcohol/pharmacology
• Rats

• genetics
• biomarkers
• cardiology
• diseases
• medical research
• nephrology

Drug-induced liver injury (DILI) is a serious health burden. It has diverse clinical presentations that can escalate to acute liver failure. The worldwide increase in the use of psychotropic drugs, their long-term use on a daily basis, common comorbidities of psychiatric and metabolic disorders, and polypharmacy in psychiatric patients increase the incidence of psychotropics-induced DILI. During the last 2 decades, hepatotoxicity of various antidepressants (ADs) and antipsychotics (APs) received much attention. Comprehensive review and discussion of accumulated literature data concerning this issue are performed in this study, as hepatotoxic effects of most commonly prescribed ADs and APs are classified, described, and discussed. The review focuses on ADs and APs characterized by the risk of causing liver damage and highlights the ones found to cause life-threatening or severe DILI cases. In parallel, an overview of hepatic oxidative stress, inflammation, and steatosis underlying DILI is provided, followed by extensive review and discussion of the pathophysiology of AD- and AP-induced DILI revealed in case reports, and animal and in vitro studies. The consequences of some ADs and APs ability to affect drug-metabolizing enzymes and therefore provoke drug–drug interactions are also addressed. Continuous collecting of data on drugs, mechanisms, and risk factors for DILI, as well as critical data reviewing, is crucial for easier DILI diagnosis and more efficient risk assessment of AD- and AP-induced DILI. Higher awareness of ADs and APs hepatotoxicity is the prerequisite for their safe use and optimal dosing.

• Antidepressants
• Antipsychotics
• Hepatotoxicity
• Inflammation
• Oxidative stress
• Steatosis

• Caffeic acid phenethyl ester
• Inflammation
• Mouse
• Neurodegeneration
• Rotenone