Effects of Atorvastatin and Simvastatin on the Bioenergetic Function of Isolated Rat Brain Mitochondria DOI Open Access

Krzysztof Wojcicki,

Adrianna Budzinska,

Wiesława Jarmuszkiewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8494 - 8494

Published: Aug. 3, 2024

Little is known about the effects of statins, which are cholesterol-lowering drugs, on bioenergetic functions mitochondria in brain. This study aimed to elucidate direct atorvastatin and simvastatin bioenergetics isolated rat brain by measuring statin-induced changes respiratory chain activity, ATP synthesis efficiency, production reactive oxygen species (ROS). Our results first demonstrate that dose-dependently significantly inhibit activity mitochondrial chain, resulting a decreased rate, membrane potential, increased ROS formation. Moreover, tested statins reduced coupling parameters, ADP/O ratio, control thus, oxidative phosphorylation efficiency mitochondria. Among complexes, impairment concerned complex I, III, synthase activity. The calcium-containing had more substantial effect than simvastatin. higher inhibitory was dependent calcium ions, may lead disruption homeostasis These findings suggest while effective their primary role as agents, use impair function, have consequences for health, particularly when energy critical.

Language: Английский

Off‐target effects of statins: molecular mechanisms, side effects and the emerging role of kinases DOI Creative Commons
Francisco Alejandro Lagunas‐Rangel, E. Liepinsh, Robert Fredriksson

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(20), P. 3799 - 3818

Published: Aug. 24, 2024

Abstract Statins are one of the most important classes drugs. In this analytical review, we elucidate intricate molecular mechanisms and toxicological rationale regarding both on‐ (targeting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase [HMGCR]) off‐target effects statins. interact with a number membrane kinases, such as epidermal growth factor receptor (EGFR), erb‐b2 tyrosine kinase 2 (HER2) MET proto‐oncogene, (MET), well cytosolic SRC non‐receptor (Src) show inhibitory activity at nanomolar concentrations. addition, they calcium ATPases peroxisome proliferator‐activated α (PPARα/NR1C1) higher mitochondrial complexes III IV, their inhibition coenzyme Q10 synthesis also impairs functioning I II. act inhibitors complexes, while activating PPARα. These likely contribute to side observed in patients undergoing statin therapy, including musculoskeletal symptoms hepatic effects. Interestingly, some statins could be cause favourable outcomes, relating repurposing conditions inflammatory disorders cancer.

Language: Английский

Citations

6
What is in the Myopathy Literature? DOI
David Lacomis, Michael Isfort

Journal of Clinical Neuromuscular Disease, Journal Year: 2025, Volume and Issue: 26(3), P. 152 - 166

Published: Feb. 26, 2025

Abstract This update begins with the incidence and features of statin-associated muscle symptoms, which may often be misattributed. Articles on potential mitochondria dysfunction from statins follow, along recommendations for possibly avoiding in some patients genetic myopathies. Next, autoimmune myopathies, including immune-mediated necrotizing myopathy, myositis antimitochondrial antibodies, overlap lupus, as well role myxovirus protein A identification specimens, are addressed. The next section includes reports significance elevated serum aldolase normal creatine kinase recommended approaches to evaluate a patient rhabdomyolysis. cluster imaging, particularly using ultrasound magnetic resonance covered. They include studies inherited inflammatory myopathies neck extensor myopathy topics such imaging features, patterns involvement, diagnostic utility, correlation histopathology. Last, there discussions mexiletine versus lamotrigine nondystrophic myotonias treatment fatty acid oxidation disorders adults.

Language: Английский

Citations

0
The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells DOI Creative Commons

Lauren Millichap,

Nadia Turton,

Razan Alomosh

et al.

Toxicology Mechanisms and Methods, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 3, 2025

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, current study has demonstrated that simvastatin induces neurotoxicity is associated with cellular coenzyme Q10 (CoQ10) depletion. CoQ10 a significant role mitochondrial electron transport chain (ETC), addition to being fundamental lipid-soluble antioxidant. Depletion impaired function increased oxidative stress. The aim this was investigate potential mechanisms simvastatin-induced assessing evidence stress an vitro SH-SY5Y human neuronal cell line. Fluorescence studies assessed via flow cytometry determined increases intracellular reactive oxygen species production following compared control cells. Additionally, spectrophotometric enzyme (p < 0.0001) inhibition ETC complex I II-III activities which accompanied decrease content 0.005) viability 0.0001). results present have indicated dysfunction stress, resulting loss treatment. Thus, these demonstrate statin therapy.

Language: Английский

Citations

0
Prolonged exposure to simvastatin affects coenzyme Q9/10 status leading to impaired mitochondrial respiratory capacity and reduced viability of cultured cardiac cells DOI Creative Commons
Sinenhlanhla X. H. Mthembu, Sithandiwe E. Mazibuko-Mbeje, Sonia Silvestri

et al.

Toxicology in Vitro, Journal Year: 2025, Volume and Issue: unknown, P. 106052 - 106052

Published: March 1, 2025

Language: Английский

Citations

0
Targeting cholesterol metabolism: a promising therapy strategy for cancer DOI

Chunlan Dai,

Zhixin Qiu, Anqi Wang

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

Citations

0
Pharmacological therapy targeting the immune response in atherosclerosis DOI

Yirong Wu,

Yizhou Xu, Linhao Xu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 112974 - 112974

Published: Aug. 23, 2024

Language: Английский

Citations

1
Effects of Atorvastatin and Simvastatin on the Bioenergetic Function of Isolated Rat Brain Mitochondria DOI Open Access

Krzysztof Wojcicki,

Adrianna Budzinska,

Wiesława Jarmuszkiewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8494 - 8494

Published: Aug. 3, 2024

Little is known about the effects of statins, which are cholesterol-lowering drugs, on bioenergetic functions mitochondria in brain. This study aimed to elucidate direct atorvastatin and simvastatin bioenergetics isolated rat brain by measuring statin-induced changes respiratory chain activity, ATP synthesis efficiency, production reactive oxygen species (ROS). Our results first demonstrate that dose-dependently significantly inhibit activity mitochondrial chain, resulting a decreased rate, membrane potential, increased ROS formation. Moreover, tested statins reduced coupling parameters, ADP/O ratio, control thus, oxidative phosphorylation efficiency mitochondria. Among complexes, impairment concerned complex I, III, synthase activity. The calcium-containing had more substantial effect than simvastatin. higher inhibitory was dependent calcium ions, may lead disruption homeostasis These findings suggest while effective their primary role as agents, use impair function, have consequences for health, particularly when energy critical.

Language: Английский

Citations

1