Propylthiouracil-induced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity

Jamshidzadeh, Akram; Niknahad, Hossein; Heidari, Reza; Maryam, Azadbakht; Khodaei, Forouzan; Reza, Arabnezhad Mohammad; Farshad, Omid

doi:10.15171/ps.2017.15

Cited by 15 publications

(9 citation statements)

References 52 publications

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“…A luciferase-luciferin-based kit from Promega (ENLITEN ® ) was used to assess mitochondrial ATP content. 44 Samples and buffer solutions were prepared based on the kit instructions, and the luminescence intensity of samples was measured at λ = 560 nm using a FLUOstar Omega ® (BMG Labtech, Germany) multifunctional microplate reader. For standardization of data, samples protein concentrations were determined by the Bradford method.…”

Section: Methodsmentioning

confidence: 99%

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

et al. 2019

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Purpose: Manganese (Mn) is a neurotoxic chemical which induces a wide range of complications in the brain tissue. Impaired locomotor activity and cognitive dysfunction are associated with high brain Mn content. At the cellular level, mitochondria are potential targets for Mn toxicity. Carnosine is a dipeptide abundantly found in human brain. Several pharmacological properties including mitochondrial protecting and antioxidative effects have been attributed to carnosine. The current study aimed to evaluate the effect of carnosine treatment on Mn-induced mitochondrial dysfunction in isolated brain mitochondria. Methods: Mice brain mitochondria were isolated based on the differential centrifugation method and exposed to increasing concentrations of Mn (10 µM-10 mM). Carnosine (1 mM) was added as the protective agent. Mitochondrial indices including mitochondrial depolarization, reactive oxygen species (ROS) formation, mitochondrial dehydrogenases activity, ATP content, and mitochondrial swelling and permeabilization were assessed. Results: Significant deterioration in mitochondrial indices were evident in Mn-exposed brain mitochondria. On the other hand, it was found that carnosine (1 mM) treatment efficiently prevented Mn-induced mitochondrial impairment. Conclusion: These data propose mitochondrial protection as a fundamental mechanism for the effects of carnosine against Mn toxicity. Hence, this peptide might be applicable against Mn neurotoxicity with different etiologies (e.g., in cirrhotic patients).

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Section: Methodsmentioning

confidence: 99%

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

et al. 2019

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“…In addition, polyphenol-rich C. morifolium extract ameliorated high-fat/drug-induced fatty liver in mice by orally feeding emulsion containing 10% cholesterol, 20% lard, and 0.2% propylthiouracil [ 14 ]. Propylthiouracil is known to cause liver injury and acute liver failure [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Antilipotoxicity Activity of Osmanthus fragrans and Chrysanthemum morifolium Flower Extracts in Hepatocytes and Renal Glomerular Mesangial Cells

Tsai

Chang

Hsin

et al. 2017

Mediators of Inflammation

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The excess influx of free fatty acids (FFAs) into nonadipose tissues, such as those of liver and kidney, induces lipotoxicity leading to hepatic steatosis and renal dysfunction. The aim of this study was to investigate the protective effects of methanolic flower extracts of Osmanthus fragrans (OF) and Chrysanthemum morifolium (CM) against FFA-induced lipotoxicity in hepatocytes (human HepG2 cells) and renal glomerular mesangial cells (mouse SV40-Mes13 cells). The results showed that OF and CM significantly suppressed FFA-induced intracellular triacylglycerol accumulation via partially inhibiting the gene expression of sterol regulatory element-binding protein-1c (SREBP-1c) and glycerol-3-phosphate acyltransferase (GPAT) in HepG2 cells. Both extracts inhibited reactive oxygen species (ROS) generation by FFA-stimulated HepG2 cells. OF and CM also suppressed the mRNA expression of interleukin- (IL-) 1β, IL-6, IL-8, tumor necrosis factor- (TNF-) α, and transforming growth factor- (TGF-) β by HepG2 cells treated with conditioned medium derived from lipopolysaccharide-treated THP-1 monocytes. Furthermore, OF and CM effectively inhibited oleate-induced cellular lipid accumulation, TGF-β secretion, and overexpression of fibronectin in mesangial cells. In conclusion, OF and CM possess hepatoprotective activity by inhibiting hepatic fat load and inflammation and renal protection by preventing FFA-induced mesangial extracellular matrix formation.

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“…The 3-(4, 5-dimethylthiazol-2-yl)-2, the 5-diphenyltetrazolium bromide (MTT) assay used to determine dehydrogenases activity in isolated renal mitochondria ( Heidari et al., 2016b , 2018c ; Niknahad et al., 2015a ; Ommati et al., 2018 ). For this purpose, a mitochondrial suspension (1 mg protein/mL) was incubated with 40 μL of MTT solution (0.4% w: v in incubation buffer) and incubated at 37 °C (30 min, in the dark) ( Akram et al., 2017 ; Heidari et al., 2019b ; Ommati et al., 2020g ). Then, samples were centrifuged (10000 g, 10 min), and the product of formazan crystals were dissolved in dimethyl sulfoxide (1000 μL).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress are involved in the mechanism of tramadol-induced renal injury

Mousavi

Manthari

Najibi

et al. 2021

Current Research in Pharmacology and Drug Discovery

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Tramadol (TMDL) is an opioid analgesic widely administered for the management of moderate to severe pain. On the other hand, TMDL is commonly abused in many countries because of its availability and cheap cost. Renal injury is related to high dose or chronic administration of TMDL. No precise mechanism for TMDL-induced renal damage has been identified so far. The current study aimed to evaluate the potential role of oxidative stress and mitochondrial impairment in the pathogenesis of TMDL-induced renal injury. For this purpose, rats were treated with TMDL (40 and 80 mg/kg, i.p, 28 consecutive days). A significant increase in serum Cr and BUN was detected in TMDL groups. On the other hand, TMDL (80 mg/kg) caused a substantial increase in urine glucose, ALP, protein, and γ-GT levels. Moreover, urine Cr was significantly decreased in TMDL-treated rats (40 and 80 mg/kg). Renal histopathological alterations included inflammation, necrosis, and tubular degeneration in the kidney of TMDL-treated animals. Reactive oxygen species (ROS) formation, increased oxidized glutathione (GSSG), lipid peroxidation, and protein carbonylation was increased, whereas total antioxidant capacity and reduced glutathione levels were considerably decreased in TMDL groups. Significant mitochondrial impairment was also detected in the form of mitochondrial depolarization, adenosine-tri-phosphate (ATP) depletion, mitochondrial permeabilization, lipid peroxidation, and decreased mitochondrial dehydrogenase activity in the kidney of TMDL (80 mg/kg)-treated animals. These data suggest mitochondrial impairment and oxidative stress as mechanisms involved in the pathogenesis of TMDL-induced renal injury.

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Propylthiouracil-induced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity

Cited by 15 publications

References 52 publications

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

Carnosine Mitigates Manganese Mitotoxicity in an In Vitro Model of Isolated Brain Mitochondria

Antilipotoxicity Activity of Osmanthus fragrans and Chrysanthemum morifolium Flower Extracts in Hepatocytes and Renal Glomerular Mesangial Cells

Mitochondrial dysfunction and oxidative stress are involved in the mechanism of tramadol-induced renal injury

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