scholarly journals Improvement of Platelet Respiration by Cell–Permeable Succinate in Diabetic Patients Treated with Statins

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 288
Author(s):  
Vlad Florian Avram ◽  
Anca Mihaela Bîna ◽  
Alexandra Sima ◽  
Oana Maria Aburel ◽  
Adrian Sturza ◽  
...  
Keyword(s):  
Side Effects ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Treatment Interruption ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Lipid Lowering Therapy ◽  
Potential Biomarker

Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first–line lipid–lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM– and statin–induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell–permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.

scholarly journals Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

2021 ◽  
Vol 22 (1) ◽  
pp. 424
Author(s):  
Vlad F. Avram ◽  
Imen Chamkha ◽  
Eleonor Åsander-Frostner ◽  
Johannes K. Ehinger ◽  
Romulus Z. Timar ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Coupling Efficiency ◽  
Human Platelets ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Cellular Models

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Subir Roy Chowdhury ◽  
Cheryl Peltier ◽  
Sen Hou ◽  
Amandeep Singh ◽  
James B. Johnston ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Ex Vivo ◽  
Standard Dose ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Clinical Tool ◽  
Potential Biomarker ◽  
Apoptotic Pathways ◽  
The Impact

Mitochondrial respiration is becoming more commonly used as a preclinical tool and potential biomarker for chronic lymphocytic leukemia (CLL) and activated B-cell receptor (BCR) signaling. However, respiration parameters have not been evaluated with respect to dose of ibrutinib given in clinical practice or the effect of progression on ibrutinib treatment on respiration of CLL cells. We evaluated the impact of low and standard dose ibrutinib on CLL cells from patients treated in vivo on mitochondrial respiration using Oroboros oxygraph. Cytokines CCL3 and CCL4 were evaluated using the Mesoscale. Western blot analysis was used to evaluate the BCR and apoptotic pathways. We observed no difference in the mitochondrial respiration rates or levels of plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4), β-2 microglobulin (β-2 M) and lactate dehydrogenase (LDH) between low and standard doses of ibrutinib. This may confirm why clinical observations of the safety and efficacy of low dose ibrutinib are observed in practice. Of interest, we also observed that the mitochondrial respiration of CLL cells paralleled the increase in β-2 M and LDH at progression. Our study further supports mitochondrial respiration as a biomarker for response and progression on ibrutinib in CLL cells and a valuable pre-clinical tool.

scholarly journals Role of Colesevelam in Combination Lipid-Lowering Therapy

2013 ◽  
Vol 13 (5) ◽  
pp. 315-323 ◽  
Author(s):  
Michael R. Jones ◽  
Oliseyenum M. Nwose
Keyword(s):  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

scholarly journals The role of soluble fiber intake in patients under highly effective lipid-lowering therapy

2011 ◽  
Vol 10 (1) ◽  
Author(s):  
Silvia C Ramos ◽  
Francisco A Fonseca ◽  
Soraia H Kasmas ◽  
Flávio T Moreira ◽  
Tatiana Helfenstein ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Fiber Intake ◽  
Soluble Fiber ◽  
Lowering Therapy ◽  
Highly Effective

scholarly journals Cross-sectional study of pattern of Dyslipidemia and Prevalence of Atherogenic Diabetic Dyslipidemia in newly detected Diabetic patients

2019 ◽  
Vol 10 (6) ◽  
pp. 45-49
Author(s):  
Vinay Krishnamurthy ◽  
Akhila Rao Kerekoppa ◽  
Prabhakar B
Keyword(s):  
Tertiary Care ◽  
Hdl Cholesterol ◽  
Cross Sectional Study ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Lipid Lowering Therapy ◽  
Newly Diagnosed ◽  
Diabetic Dyslipidemia ◽  
Cross Sectional ◽  
Treatment Naïve

Background: India has seen an ever increasing number of diabetic patients and in turn rise in cardiovascular diseases. Many studies have shown diabetic patients to have dyslipidemia, with certain common patterns early in the disease. Aims and Objective: The current study was done to identify pattern of dyslipidemia and prevalence of ADD in treatment naïve diabetic patients. Material and Methods: Fasting lipid profile was analysed in treatment naïve diabetic patients at a tertiary care teaching hospital. Various factors influencing the results were analysed statistically. Results: Prevalence of dyslipidemia was 89.2%, whereasatherogenic diabetic dyslipidemia was seen in 34.2% and raised non-HDL cholesterol in 73.3%. Conclusion: Our study showed a high prevalence of dyslipidemia in newly diagnosed diabetics indicating the importance of screening for dyslipidemia in newly diagnosed cases and implementation of timely lipid lowering therapy to prevent CVD. It also highlights the importance of pattern of dyslipidemia called Atherogenic diabetic dyslipidemia and raised Non-HDL cholesterol in diabetic patients.

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