Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury

Heidari, Reza; Jamshidzadeh, Akram; Ommati, Mohammad Mehdi; Rashidi, Elaheh; Khodaei, Forouzan; Sadeghi, Ala; Hosseini, A. Zavaran; Niknahad, Hossein

doi:10.5114/ceh.2019.85071

Cited by 20 publications

(14 citation statements)

References 60 publications

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“…Water and acetate (Buffers A; 4:1 v: v) along with a mixture of methanol with buffer A (Buffers B; 4:1 v: v) were considered as the mobile phases (flow rate = 1 mL/min). A gradient technique with a constant upsurge of buffer B to 95% in 25 min was applied ( 70 ). Samples (500 μL of testis homogenate) was treated with 50 μL of TCA (50% w: v, 4°C, in MiliQ water).…”

Section: Methodsmentioning

confidence: 99%

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

et al. 2021

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Lithium (Li+) is prescribed against a wide range of neurological disorders. Besides its excellent therapeutic properties, there are several adverse effects associated with Li+. The impact of Li+ on renal function and diabetes insipidus is the most common adverse effect of this drug. On the other hand, infertility and decreased libido is another complication associated with Li+. It has been found that sperm indices of functionality, as well as libido, is significantly reduced in Li+-treated men. These adverse effects might lead to drug incompliance and the cessation of drug therapy. Hence, the main aims of the current study were to illustrate the mechanisms of adverse effects of Li+ on the testis tissue, spermatogenesis process, and hormonal changes in two experimental models. In the in vitro experiments, Leydig cells (LCs) were isolated from healthy mice, cultured, and exposed to increasing concentrations of Li+ (0, 10, 50, and 100 ppm). In the in vivo section of the current study, mice were treated with Li+ (0, 10, 50, and 100 ppm, in drinking water) for five consecutive weeks. Testis and sperm samples were collected and assessed. A significant sign of cytotoxicity (LDH release and MTT assay), along with disrupted testosterone biosynthesis, impaired mitochondrial indices (ATP level and mitochondrial depolarization), and increased biomarkers of oxidative stress were detected in LCs exposed to Li+. On the other hand, a significant increase in serum and testis Li+ levels were detected in drug-treated mice. Moreover, ROS formation, LPO, protein carbonylation, and increased oxidized glutathione (GSSG) were detected in both testis tissue and sperm specimens of Li+-treated mice. Several sperm anomalies were also detected in Li+-treated animals. On the other hand, sperm mitochondrial indices (mitochondrial dehydrogenases activity and ATP levels) were significantly decreased in drug-treated groups where mitochondrial depolarization was increased dose-dependently. Altogether, these data mention oxidative stress and mitochondrial impairment as pivotal mechanisms involved in Li+-induced reproductive toxicity. Therefore, based on our previous publications in this area, therapeutic options, including compounds with high antioxidant properties that target these points might find a clinical value in ameliorating Li+-induced adverse effects on the male reproductive system.

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Section: Methodsmentioning

confidence: 99%

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

et al. 2021

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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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“…Previous studies mentioned that the cellular mechanism underlying the nephrotoxicity induced by several drugs is associated with oxidative stress and mitochondrial impairment [ 101 ] (Figure 3). Mitochondria are essential organelles in kidney tissue.…”

Section: Organ Injury As a Feature Of Drugs Used In Covid‐19 Pharmacomentioning

confidence: 99%

Drug‐induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies

Ommati

Mobasheri

Heidari

2021

J Biochem & Molecular Tox

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The world is currently facing an unprecedented pandemic caused by a newly recognized and highly pathogenic coronavirus disease 2019 (COVID‐19; induced by SARS‐CoV‐2 virus), which is a severe and ongoing threat to global public health. Since COVID‐19 was officially declared a pandemic by the World Health Organization in March 2020, several drug regimens have rapidly undergone clinical trials for the management of COVID‐19. However, one of the major issues is drug‐induced organ injury, which is a prominent clinical challenge. Unfortunately, most drugs used against COVID‐19 are associated with adverse effects in different organs, such as the kidney, heart, and liver. These side effects are dangerous and, in some cases, they can be lethal. More importantly, organ injury is also a clinical manifestation of COVID‐19 infection. These adverse reactions are increasingly recognized as outcomes of COVID‐19 infection. Therefore, the differential diagnosis of drug‐induced adverse effects from COVID‐19‐induced organ injury is a clinical complication. This review highlights the importance of drug‐induced organ injury, its known mechanisms, and the potential therapeutic strategies in COVID‐19 pharmacotherapy. We review the potential strategies for the differential diagnosis of drug‐induced organ injury. This information can facilitate the development of therapeutic strategies, not only against COVID‐19 but also for future outbreaks of other emerging infectious diseases.

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Ammonia-induced mitochondrial impairment is intensified by manganese co-exposure: relevance to the management of subclinical hepatic encephalopathy and cirrhosis-associated brain injury

Cited by 20 publications

References 60 publications

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

The Role of Mitochondrial Impairment and Oxidative Stress in the Pathogenesis of Lithium-Induced Reproductive Toxicity in Male Mice

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

Drug‐induced organ injury in coronavirus disease 2019 pharmacotherapy: Mechanisms and challenges in differential diagnosis and potential protective strategies

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