In Vitro and In Vivo Evidence on the Role of Mitochondrial Impairment as a Mechanism of Lithium-Induced Nephrotoxicity

Ommati, Mohammad Mehdi; Niknahad, Hossein; Farshad, Omid; Azarpira, Negar; Heidari, Reza

doi:10.1007/s12011-020-02302-9

Cited by 25 publications

(11 citation statements)

References 44 publications

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“…Lithium, the first-line drug treatment for BD, both for bipolar depression [256][257][258][259][260][261] and for mixed episodes [262][263][264][265][266][267][268][269][270][271][272][273][274] has numerous neuroprotective, neurotrophic, and neuroplastic effects [275][276][277][278]. In addition to being the mood stabilizer conventionally used in ameliorating the pathophysiology of BD, lithium has some antidepressant activity [279][280][281][282]. The therapeutic effects of lithium have been hypothesized to be partially linked to its antioxidant capabilities.…”

Section: Lithium Therapymentioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive–behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

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Section: Lithium Therapymentioning

confidence: 99%

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Madireddy

2022

IJMS

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“…Urine samples were collected (200 µl) during animal handling and diluted with ice-cold normal saline (200 µl, 4°C) [ 32 , 33 ]. Afterward, samples were centrifuged (1000 g, 5 min, 4°C), and the clear supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

“…Renal glutathione (GSH and GSSG) content was measured using HPLC [ 32 , 52 , 53 ]. Briefly, tissue homogenate (1 ml) was treated with 100 µl of ice-cooled perchloric acid (10%), mixed well, incubated on ice (15 min), and then centrifuged (17,000 g, 30 min, 4°C) [ 52 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Ommati¹,

Hojatnezhad²,

Abdoli³

et al. 2021

ceh

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Aim of the study Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated. Material and methods Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored. Results Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines. Conclusions These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

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“…Urine samples were collected (200 μL) were collected during animal handling, diluted with ice-cooled normal saline (200 μL, 4 °C), and centrifuged (1000 g, 10 min, 4 °C) ( Ommati et al., 2020 ; Ommati et al., 2020 ). The clear supernatant was used for urinalysis.…”

Section: Methodsmentioning

confidence: 99%

Suppression of cirrhosis-related renal injury by N-acetyl cysteine

Abdoli

Sadeghian

Mousavi

et al. 2020

Current Research in Pharmacology and Drug Discovery

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Cirrhosis-induced renal injury or cholemic nephropathy (CN) is a serious clinical complication with poor prognosis. CN could finally lead to renal failure and the need for organ transplantation. Unfortunately, there is no specific pharmacological intervention against CN to date. On the other hand, various studies mentioned the role of oxidative stress and mitochondrial impairment in the pathogenesis of CN. The current study aimed to evaluate the potential protective effects of NAC as a thiol-reducing agent and antioxidant in CN. Bile duct ligation (BDL) was used as a reliable animal model of cholestasis. BDL animals received NAC (0.25% and 1% w: v) in drinking water for 28 consecutive days. Finally, urine, blood, and kidney samples were collected and analyzed. Significant elevation in serum biomarkers of renal injury, along with urine markers of kidney damage, was evident in the BDL group. Moreover, markers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, protein carbonylation, and increased oxidized glutathione (GSSG) were evident detected in the kidney of cholestatic rats. Renal tissue antioxidant capacity and reduced glutathione (GSH) were also significantly depleted in the BDL group. Significant mitochondrial depolarization, depleted ATP content, and mitochondrial permeabilization was also detected in mitochondria isolated from the kidney of cholestatic animals. Renal histopathological alterations consisted of significant tissue fibrosis, interstitial inflammation, and tubular atrophy. It was found that NAC (0.25 and 1% in drinking water for 28 consecutive days) blunted histopathological changes, decreased markers of oxidative stress, and improved mitochondrial indices in the kidney of cirrhotic rats. Moreover, serum and urine biomarkers of renal injury were also mitigated in upon NAC treatment. These data indicate a potential renoprotective role for NAC in cholestasis. The effects of NAC on cellular redox state and mitochondrial function seem to play a fundamental role in its renoprotective effects during CN.

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In Vitro and In Vivo Evidence on the Role of Mitochondrial Impairment as a Mechanism of Lithium-Induced Nephrotoxicity

Cited by 25 publications

References 44 publications

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress–Induced Damage in Patients with Bipolar Disorder

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Suppression of cirrhosis-related renal injury by N-acetyl cysteine

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