Mitochondria‐Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic‐Induced Toxicity

Raza, Haider; Guengerich, F. Peter; Avadhani, Narayan G.

doi:10.1002/9781119329725.ch4

Cited by 2 publications

(3 citation statements)

References 92 publications

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“…[ 13 ] Alteration in mitochondrial dynamics lead to mitochondrial toxicity and mitochondrial dysfunction. [ 13 ] Mitochondrial dysfunction has been reported in a number of drug‐induced toxicities. [ 14 ] Drug‐induced mitochondrial toxicity leading to a wide range of pathological conditions such as neurotoxicity, hepatotoxicity, nephrotoxicity, cardiotoxicity, and other disorders.…”

Section: Introductionmentioning

confidence: 99%

“…[11] Several studies have reported that a number of ER-associated CYPs such as 1A, 1B, 2B, 2C, 2D, 2E, and 3A are also located inside the inner membrane compartment of mitochondria facing the matrix. [12,13] Mitochondrial metabolic enzyme systems, genome, and membrane complexes are highly sensitive to alterations in intramitochondrial as well as extramitochondrial environments, resulting in mitochondrial dynamic changes (biogenesis, fission, fusion, mass, mitophagy). [13] Alteration in mitochondrial dynamics lead to mitochondrial toxicity and mitochondrial dysfunction.…”

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confidence: 99%

“…[12,13] Mitochondrial metabolic enzyme systems, genome, and membrane complexes are highly sensitive to alterations in intramitochondrial as well as extramitochondrial environments, resulting in mitochondrial dynamic changes (biogenesis, fission, fusion, mass, mitophagy). [13] Alteration in mitochondrial dynamics lead to mitochondrial toxicity and mitochondrial dysfunction. [13] Mitochondrial dysfunction has been reported in a number of drug-induced toxicities.…”

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confidence: 99%

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Evaluation of in vitro effects of ifosfamide drug on mitochondrial functions using isolated mitochondria obtained from vital organs

Salimi,

Khezri,

Azizian

et al. 2023

J Biochem & Molecular Tox

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Mitochondrial toxicity has been shown to contribute to a variety of organ toxicities such as, brain, heart, kidney, and liver. Ifosfamide (IFO) as an anticancer drug, is associated with increased risk of neurotoxicity, cardiotoxicity nephrotoxicity, hepatotoxicity, and hemorrhagic cystitis. The aim of this study was to evaluate the direct effect of IFO on isolated mitochondria obtained from the rat brain, heart, kidney, and liver. Mitochondria were isolated with mechanical lysis and differential centrifugation from different organs and treated with various concentrations of IFO. Using biochemical and flowcytometry assays, we evaluated mitochondrial succinate dehydrogenase (SDH) activity, mitochondrial swelling, lipid peroxidation, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP). Our data showed that IFO did not cause deleterious alterations in mitochondrial functions, mitochondrial swelling, lipid peroxidation ROS formation, and MMP collapse in mitochondria isolated from brain, heart, kidney, and liver. Altogether, the data showed that IFO is not directly toxic in mitochondria isolated from brain, heart, kidney, and liver. This study proved that mitochondria alone does not play the main role in the toxicity of IFO, and suggests to reduce the toxicity of this drug, other pathways resulting in the production of toxic metabolites should be considered.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Evaluation of in vitro effects of ifosfamide drug on mitochondrial functions using isolated mitochondria obtained from vital organs

Salimi,

Khezri,

Azizian

et al. 2023

J Biochem & Molecular Tox

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CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan

Lim,

Pan,

Alshagga

et al. 2024

J of Applied Toxicology

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CYP‐14 members of the Caenorhabditis elegans (C. elegans) Cytochrome P450 (CYP) enzyme family, plays important roles in mitochondrial dysfunction, detoxification, lipid metabolism, defense and lifespan regulation. The review identifies CYP‐14 members: cyp‐14A1, cyp‐14A2, cyp‐14A3, cyp‐14A4, cyp‐14A5 and their homology with human CYP families. Despite limited studies on C. elegans cyp‐14 members, the findings unraveled their complex crosstalk between mitochondrial stress, detoxification mechanisms, and lifespan regulation, emphasizing the complexity of these interconnected pathways as well as how their regulation depends on environmental cues changes including pH, nutrients, ROS and chemical stressors. The review underscores the translational relevance to human health, shedding light on potential human homologues and their implications in age‐related, metabolic and respiratory diseases. Among other genes, cyp‐14A2 and cyp‐14A4 predominate the mitochondrial function, heat resistance, lipid metabolism, detoxification and lifespan pathways. In conclusion, these insights pave the way for future research, offering promising avenues for therapeutic interventions targeting CYP‐14 activity to address age‐related diseases and promote healthy aging.

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Mitochondria‐Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic‐Induced Toxicity

Cited by 2 publications

References 92 publications

Evaluation of in vitro effects of ifosfamide drug on mitochondrial functions using isolated mitochondria obtained from vital organs

Evaluation of in vitro effects of ifosfamide drug on mitochondrial functions using isolated mitochondria obtained from vital organs

CYP14 family in Caenorhabditis elegans: Mitochondrial function, detoxification, and lifespan

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