Toxicity of Pioglitazone on Mitochondria Isolated from Brain and Heart: An Analysis for Probable Drug-Induced Neurotoxicity and Cardiotoxicity

Seydi, Enayatollah; Servati, Tina; Samiei, Fatemeh; Naserzadeh, Parvaneh; Pourahmad, Jalal

doi:10.1055/a-1085-2542

Cited by 9 publications

(5 citation statements)

References 43 publications

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“…Metformin and pioglitazone inhibit the activity of complex I of the mitochondrial respiratory chain [ 115 , 116 , 117 ]. Pioglitazone at high concentrations induces mitochondrial swelling, increases ROS production, and decreases the membrane potential of mitochondria [ 118 ].…”

Section: Mechanisms Of the Diabetes-induced Mitochondrial Dysfunctmentioning

confidence: 99%

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

Belosludtsev

Belosludtseva

Dubinin

2020

IJMS

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Diabetes mellitus is one of the most common metabolic diseases in the developed world, and is associated either with the impaired secretion of insulin or with the resistance of cells to the actions of this hormone (type I and type II diabetes, respectively). In both cases, a common pathological change is an increase in blood glucose—hyperglycemia, which eventually can lead to serious damage to the organs and tissues of the organism. Mitochondria are one of the main targets of diabetes at the intracellular level. This review is dedicated to the analysis of recent data regarding the role of mitochondrial dysfunction in the development of diabetes mellitus. Specific areas of focus include the involvement of mitochondrial calcium transport systems and a pathophysiological phenomenon called the permeability transition pore in the pathogenesis of diabetes mellitus. The important contribution of these systems and their potential relevance as therapeutic targets in the pathology are discussed.

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Section: Mechanisms Of the Diabetes-induced Mitochondrial Dysfunctmentioning

confidence: 99%

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

Belosludtsev

Belosludtseva

Dubinin

2020

IJMS

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“…In addition, changes in mitochondrial energy metabolism, such as decreased maximal respiration, indicate damage to the mitochondrial respiratory chain and abnormal energy metabolism [64]. Lastly, by the mitochondrial ultrastructure, the appearance of swollen [65] mitochondria and autophagic bodies [66] in the brain tissues of mice in the Alp group reflected the mitochondrial dynamics imbalance and impaired autophagy function. Several studies have focused on the effects of mitochondrial dysfunction in learning and memory.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice

Zhu,

Shi,

Jin

et al. 2023

Aging

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The frequently repeated administration of alprazolam (Alp), a highly effective benzodiazepine sedative-hypnotic agent, in anxiety, insomnia, and other diseases is closely related to many negative adverse reactions that are mainly manifested as memory impairment. However, the exact molecular mechanisms underlying these events are poorly understood. Therefore, we conducted a proteomic analysis on the hippocampus in mice that received repeated administration of Alp for 24 days. A total of 439 significantly differentially expressed proteins (DEPs) were identified in mice with repeated administration of Alp compared to the control group, and the GO and KEGG analysis revealed the enrichment of terms related to mitochondrial function, cycle, mitophagy and cognition. In vitro experiments have shown that Alp may affect the cell cycle, reduce the mitochondrial membrane potential (MMP) to induce apoptosis in HT22 cells, and affect the progress of mitochondrial energy metabolism and morphology in the hippocampal neurons. Furthermore, in vivo behavioral experiments including IntelliCage System (ICS) and nover object recognition (NOR), hippocampal neuronal pathological changes with HE staining, and the expression levels of brain-deprived neuron factor (BDNF) with immunohistochemistry showed a significant decrease in memory consolidation in mice with repeated administration of Alp, which could be rescued by the co-administration of the mitochondrial protector NSI-189. To the best of our knowledge, this is the first study to identify a link between repeated administration of Alp and mitochondrial dysfunction and that mitochondrial impairment directly causes the attenuation of memory consolidation in mice.

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“…Furthermore, this drug inhibits mitochondrial oxidative stress and inflammation and improves mitochondrial biogenesis, dynamics, and function by activating the PPAR-γ/PGC-1α signaling pathway [51]. The treatment with pioglitazone (12.5, 25, and 50 µg/mL) may exert some side effects, such as the generation of ROS, reduction of mitochondrial membrane potential, mitochondrial swelling, and release of cytochrome C, as observed in mitochondria isolated from the brain and heart of Wistar rats [52]. An analysis of health insurance records discovered that diabetic patients who received pioglitazone had a lower risk of dementia (decreased by 23%) during the 5-year follow-up period.…”

Section: Alternative Molecular Targets For Neurodegeneration: Mitocho...mentioning

confidence: 99%

Exploring Molecular Targets for Mitochondrial Therapies in Neurodegenerative Diseases

Plascencia-Villa

Perry

2023

IJMS

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The progressive deterioration of function and structure of brain cells in neurodegenerative diseases is accompanied by mitochondrial dysfunction, affecting cellular metabolism, intracellular signaling, cell differentiation, morphogenesis, and the activation of programmed cell death. However, most of the efforts to develop therapies for Alzheimer’s and Parkinson’s disease have focused on restoring or maintaining the neurotransmitters in affected neurons, removing abnormal protein aggregates through immunotherapies, or simply treating symptomatology. However, none of these approaches to treating neurodegeneration can stop or reverse the disease other than by helping to maintain mental function and manage behavioral symptoms. Here, we discuss alternative molecular targets for neurodegeneration treatments that focus on mitochondrial functions, including regulation of calcium ion (Ca2+) transport, protein modification, regulation of glucose metabolism, antioxidants, metal chelators, vitamin supplementation, and mitochondrial transference to compromised neurons. After pre-clinical evaluation and studies in animal models, some of these therapeutic compounds have advanced to clinical trials and are expected to have positive outcomes in subjects with neurodegeneration. These mitochondria-targeted therapeutic agents are an alternative to established or conventional molecular targets that have shown limited effectiveness in treating neurodegenerative diseases.

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Toxicity of Pioglitazone on Mitochondria Isolated from Brain and Heart: An Analysis for Probable Drug-Induced Neurotoxicity and Cardiotoxicity

Cited by 9 publications

References 43 publications

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice

Exploring Molecular Targets for Mitochondrial Therapies in Neurodegenerative Diseases

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