Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction

Ahmadian, Elham; Babaei, Hossein; Nayebi, Alireza Mohajjel; Eftekhari, Aziz; Eghbal, Mohammad Ali

doi:10.15171/apb.2016.066

Cited by 50 publications

(30 citation statements)

References 53 publications

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“…Thus, introducing novel protective agents in drug-induce toxicity has been an important agenda to many researchers. 31 Converging evidence has shown that INH induces hepatotoxicity within the production of active metabolites which bind covalently to cellular biomacromulcules resulting in necrosis and steatosis as a clinical manifestation of toxicity. 32 The INH metabolite, hydrazine, causes diverse liver damages such as hepatocyte necrosis, vacuolation, and inflammation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

et al. 2018

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Background: Drug-induced liver injury is a critical clinical complication. Hence, finding new and safe protective agents with potential clinical application is of value. Isoniazid (INH) is an antituberculosis agent widely used against Mycobacterium tuberculosis infection in human. On the other hand, hepatotoxicity is a clinical complication associated with isoniazid therapy. Oxidative stress and its associated events are major mechanisms identified for INH-induced liver injury. Carnosine is an endogenously found peptide widely investigated for its hepatoprotective effects. On the other hand, robust antioxidant and cytoprotective effects have been attributed to this peptide. Methods: The current study designed to evaluate the potential cytoprotective properties of carnosine against INH-induced cytotoxicity in drug-exposed primary cultured rat hepatocytes. Primary cultured rat hepatocytes were incubated with INH (1.2 mM). Results: INH treatment caused significant increase in cell death and lactate dehydrogenase (LDH) release. On the other hand, it was found that markers of oxidative stress including reactive oxygen species were significantly increased in INH-treated cells. Cellular glutathione reservoirs were also depleted in INH-treated group. Carnosine treatment (50 and 100 µM) significantly diminished INH-induced oxidative stress and cytotoxicity. Conclusion: These data mention carnosine as a potential protective agent with therapeutic capability against INH hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

et al. 2018

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“…Briefly, 1 mL of hepatocytes suspension (10 6 cells/mL) was treated with 250 μL trichloroacetic acid (TCA 70% w/v) and centrifuged at 3000 g for 15min; then 1mL of thiobarbituric acid (TBA 0.8% w/v) was added to supernatant while boiling for 20 min. The absorbance was determined at 532 nm in an Ultrospec® 2000 UV spectrophotometer …”

Section: Methodsmentioning

confidence: 99%

Protective effects of coenzyme Q10 nanoparticles on dichlorvos‐induced hepatotoxicity and mitochondrial/lysosomal injury

Eftekhari

Ahmadian

Azami

et al. 2017

Environmental Toxicology

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Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In DDVP-treated and non-treated hepatocytes in the presence of CoQ10-NPs, cell viability, the level of reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, and cellular glutathione (GSH) content were measured. The prepared CoQ10-NPs were mono-dispersed and had narrow size distribution with average diameter of 54 nm. In the in vivo study, we evaluated the enzymes, which are involved in the antioxidant system for maintenance of normal liver function. In comparison to nonparticulate CoQ10, the CoQ10-NPs efficiently decreased the ROS formation, lipid peroxidation and cell death. Also, particulate form of CoQ10 improved MMP, GSH level and lysosome membrane integrity. In the in vivo, study, we revealed that CoQ10-NPs were better hepatoprotective than its nonparticulate form (P < .05). Altogether, we propose that the CoQ10-NPs have potential capability to be used as a therapeutic and prophylactic agent for poisoning that is induced by organophosphate agents, especially in the case of DDVP. Furthermore, these positive remarks make this nanoparticle amenable for the treatment of xenobiotic-induced liver diseases.

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“…The mitochondrial ROS formation was estimated using the fluorescent probe DCFH-DA. 32,44,45 Briefly, isolated liver mitochondria were incubated in a respiratory buffer containing 125 mM sucrose, sodium succinate 5 mM, 65 mM KCl, 10 mM HEPES, 20 µM Ca 2+ , pH = 7.2 . 32 Following this step, DCFH-DA was added (Final concentration, 10 μM) to mitochondria and then incubated for 30 min at 37ºC.…”

Section: Reactive Oxygen Species (Ros) In Isolated Liver Mitochondriamentioning

confidence: 99%

“…Then, the fluorescence intensity of DCF was measured using a FLUOstar Omega ® multifunctional fluorescent microplate reader (λ excitation = 485 nm and λ emission = 525 nm). 32,45 Lipid peroxidation in liver mitochondria Thiobarbituric acid reactive substances (TBARS) were assessed as an index of lipid peroxidation in isolated kidney mitochondria as previously described. 32,41 Briefly, isolated mitochondria were washed to remove sucrose in an ice-cold buffer of MOPS-KCl (50 mM MOPS, 100 mM KCl, pH = 7.4, 4ºC), and re-suspended in fresh MOPS-KCl buffer.…”

Section: Reactive Oxygen Species (Ros) In Isolated Liver Mitochondriamentioning

confidence: 99%

Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

et al. 2019

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Background: The xenobiotics-induced liver injury is a clinical complication. Hence, finding new hepatoprotective strategies has clinical value. Oxidative stress and its subsequent complications are major mechanisms involved in xenobiotics-induced hepatotoxicity. Boldine is one of the most potent antioxidant molecules widely investigated for its protective properties in different experimental models. In the current study, the hepatoprotective properties of boldine and its potential mechanisms of hepatoprotection have been investigated. Methods: Rats received thioacetamide (TAA; 200 mg/kg, i.p) as a model of acute liver injury. Boldine (5, 10, 1nd 20 mg/kg; 24 hours intervals; oral) was administered as the hepatoprotective agent. Results: Liver injury was evident in TAA-treated animals (48 hours after TAA exposure) as a severe increase in serum level of liver injury biomarkers and histopathological alterations. Moreover, markers of oxidative stress were increased in liver tissue of TAA-treated rats. Assessment of mitochondrial indices of functionality revealed a significant decrease in mitochondrial dehydrogenases activity, the collapse of mitochondrial membrane potential, mitochondrial swelling and depletion of ATP content. It was found that boldine supplementation mitigated liver tissue markers of oxidative stress and improved mitochondrial indices of functionality in TAA-treated animals. Conclusion: The hepatoprotective properties of boldine might primarily rely on antioxidant and mitochondria protecting effects of this alkaloid.

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Venlafaxine-Induced Cytotoxicity Towards Isolated Rat Hepatocytes Involves Oxidative Stress and Mitochondrial/Lysosomal Dysfunction

Cited by 50 publications

References 53 publications

Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

Cytoprotective Properties of Carnosine against Isoniazid-Induced Toxicity in Primary Cultured Rat Hepatocytes

Protective effects of coenzyme Q10 nanoparticles on dichlorvos‐induced hepatotoxicity and mitochondrial/lysosomal injury

Boldine Supplementation Regulates Mitochondrial Function and Oxidative Stress in a Rat Model of Hepatotoxicity

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