Clinical Implications of Mitochondrial Dysfunction

2006 ◽  
Vol 105 (4) ◽  
pp. 819-837 ◽  
Author(s):  
Stanley Muravchick ◽  
Richard J. Levy ◽  
David C. Warltier
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Anesthetic Management ◽  
Metabolic Energy ◽  
Surgical Patients ◽  
Clinical Implications ◽  
Anesthetic Agents ◽  
Mitochondrial Functions ◽  
The Many

Mitochondria produce metabolic energy, serve as biosensors for oxidative stress, and eventually become effector organelles for cell death through apoptosis. The extent to which these manifold mitochondrial functions are altered by previously unrecognized actions of anesthetic agents seems to explain and link a wide variety of perioperative phenomena that are currently of interest to anesthesiologists from both a clinical and a scientific perspective. In addition, many surgical patients may be at increased perioperative risk because of inherited or acquired mitochondrial dysfunction leading to increased oxidative stress. This review summarizes the essential aspects of the bioenergetic process, presents current knowledge regarding the effects of anesthetics on mitochondrial function and the extent to which mitochondrial state determines anesthetic requirement and potential anesthetic toxicity, and considers some of the many implications that our knowledge of mitochondrial dysfunction poses for anesthetic management and perioperative medicine.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

scholarly journals Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

2019 ◽  
Vol 8 (9) ◽  
pp. 1385 ◽  
Author(s):  
Burgos-Morón ◽  
Abad-Jiménez ◽  
Marañón ◽  
Iannantuoni ◽  
Escribano-López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Β Cells ◽  
The Relationship ◽  
And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

scholarly journals Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Anastasia Agapouda ◽  
Veronika Butterweck ◽  
Matthias Hamburger ◽  
Dalene de Beer ◽  
Elizabeth Joubert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Hot Water ◽  
Human Neuroblastoma ◽  
Atp Production ◽  
Physiological Conditions ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

scholarly journals IMMUNE AGING AND SERIOUS CLINICAL IMPLICATIONS IN THE ELDERLY IN COVID-19

2021 ◽  
Vol 1 (5) ◽  
pp. e1553
Author(s):  
Eduardo Lopes Barbosa ◽  
Estéphany Miranda Dias ◽  
Letícia Lorem Vilhena de Castro ◽  
Maysa de Vasconcelos Brito
Keyword(s):  
Oxidative Stress ◽  
Intensive Care ◽  
Current Knowledge ◽  
The Elderly ◽  
Clinical Implications ◽  
Low Grade ◽  
Life Threatening ◽  
The Individual ◽  
T Cell Senescence ◽  
And Oxidative Stress

COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in most healthy precedents, but can cause life-threatening illnesses or persistent debilitating symptoms in some cases. The severity of COVID-19 is related to age, with an obligation over 65 years of age, greater risk of needing intensive care. This is a descriptive, exploratory, integrative literature review, with the aim of explaining the current knowledge about the interference of the immunosenescence process in more severe conditions caused by covid-19 in the elderly. Aging is a systemic involution, including the immune system, affecting the individual with several comorbidities, including cardiac, pulmonary and neurological comorbidities that aggravate the situation of vulnerability. Aging is triggered by several mechanisms, among the most relevant are telomere reduction and oxidative stress, which in turn lead to other scenarios such as T-cell senescence, mitochondrial dysfunction and low-grade chronic inflammation, which are added to the mechanism of action of the virus that causes COVID-19, as its key-lock factor involving ACE-2, which has a change in expression during aging, portraying the interferences of this scenario, if not in contact with the major covid-19, which contributes to seriousness in the elderly .

Bilirubin and Epigenetic Modifications in Metabolic and Immunometabolic Disorders

2021 ◽  
Vol 21 ◽  
Author(s):  
Mostafa Moradi Sarabi ◽  
Esmaeel Babaeenezhad ◽  
Maral Amini ◽  
Mozhgan Kaviani ◽  
Fakhraddin Naghibalhossaini
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Waste Product ◽  
Epigenetic Modifications ◽  
Mechanisms Of Toxicity ◽  
High Concentrations ◽  
The Brain

: Bilirubin is the main waste product of heme catabolism. At high concentrations, bilirubin may cause toxicity, especially in the brain, kidney, and erythrocytes. Membrane and mitochondrial dysfunction, oxidative stress, apoptosis, necrosis, endoplasmic reticulum stress, excitotoxicity, inflammation, and epigenetic modifications are the main mechanisms of toxicity triggered by bilirubin in susceptible organs. Many studies have shown that there is an interaction between bilirubin and epigenetic modifications in metabolic and immune diseases. In this review, we first outline the toxicity mediated by bilirubin and then summarize the current knowledge linking bilirubin and epigenetic modifications in metabolic and immunometabolic disorders.

scholarly journals Placental Ageing in Adverse Pregnancy Outcomes: Telomere Shortening, Cell Senescence, and Mitochondrial Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Samprikta Manna ◽  
Cathal McCarthy ◽  
Fergus P. McCarthy
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Pregnancy Outcomes ◽  
Current Knowledge ◽  
Neonatal Morbidity ◽  
Adverse Pregnancy Outcomes ◽  
Premature Ageing ◽  
Dna Mutations ◽  
Critical Organ ◽  
Adverse Pregnancy

Preeclampsia is a multisystemic pregnancy disorder and a major cause of maternal and neonatal morbidity and mortality worldwide. The exact pathophysiology of preeclampsia remains unclear; however, it is speculated that the various pathologies can be attributed to impaired vascular remodelling and elevated oxidative stress within the placenta. Oxidative stress plays a key role in cell ageing, and the persistent presence of elevated oxidative stress precipitates cellular senescence and mitochondrial dysfunction, resulting in premature ageing of the placenta. Premature ageing of the placenta is associated with placental insufficiency, which reduces the functional capacity of this critical organ and leads to abnormal pregnancy outcomes. The changes brought about by oxidative insults are irreversible and often lead to deleterious modifications in macromolecules such as lipids and proteins, DNA mutations, and alteration of mitochondrial functioning and dynamics. In this review, we have summarized the current knowledge of placental ageing in the aetiology of adverse pregnancy outcomes and discussed the hallmarks of ageing which could be potential markers for preeclampsia and fetal growth restriction.

scholarly journals Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Pasquale Picone ◽  
Domenico Nuzzo ◽  
Luca Caruana ◽  
Valeria Scafidi ◽  
Marta Di Carlo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Mitochondrial Protein ◽  
Radical Scavenging ◽  
Permeability Transition ◽  
Oxidation Potential ◽  
Mitochondrial Functions

Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloidβpeptide (Aβ), an important component in Alzheimer’s disease (AD) pathogenesis, and Aβcan interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of Aβ. In particular we review data concerning Aβimport into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed.

scholarly journals The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Ezgi Civi Bayin ◽  
Sermin Genc ◽  
Kursad Genc
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Common Denominator ◽  
Related Factor ◽  
Neuron Death ◽  
Promising Therapeutic Approach ◽  
Mitochondrial Functions

Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach.

scholarly journals Anesthetic Management of the Pregnant Patient: Part 1

2021 ◽  
Vol 68 (1) ◽  
pp. 52-62
Author(s):  
Jaimin Shin
Keyword(s):  
Dental Treatment ◽  
Anesthetic Management ◽  
Pregnant Patient ◽  
Developed Countries ◽  
Anesthetic Agents ◽  
Dental Procedures ◽  
Dental Patient ◽  
The Many ◽  
Dental Providers ◽  
The Impact

As delays in the age for a mother's first pregnancy continue to trend upward globally, particularly in developed countries, many pregnant patients are increasingly educated on the importance of obtaining dental care throughout their pregnancies. Guidelines set forth by the American Dental Association and the American College of Obstetrics and Gynecologists highlight the importance of dental treatment for optimizing maternal-fetal health across all trimesters, especially for emergent dental issues. The pregnant dental patient undergoes significant physiologic remodeling unique to each trimester, which may complicate treatment. Providing safe anxiety and pain control for dentistry can be further complicated if sedation or general anesthesia is required for the parturient. This is even more true when superimposed with increasingly prevalent underlying comorbidities like hypertension and diabetes. As dental providers, there is a clear need for continuing education on the many challenges associated with caring for pregnant patients due to this being an often overlooked subject in undergraduate and postgraduate dental education. Part 1 of this review will present the maternal and fetal physiologic considerations and the impact on patient management from an anesthetic perspective. Additional discussion focusing on common sedative and anesthetic agents used during dental procedures and their considerations will follow in Part 2.

Anesthesia for rabbits submitted to experimental surgeries: Report of a series of eight anesthesias

2020 ◽  
pp. 151-158
Author(s):  
Rafael Antonio Caldart Bedin ◽  
Maisa Schultz ◽  
Antonio Bedin
Keyword(s):  
Muscle Relaxation ◽  
Anesthetic Management ◽  
Laboratory Animals ◽  
Average Weight ◽  
Anesthetic Induction ◽  
Anesthetic Agents ◽  
Reasonable Degree ◽  
Bioethical Debate ◽  
Precordial Stethoscope

Anesthesia for laboratory animals is a matter of biomedical concern and one of the most present dilemmas in the current bioethical debate. The use of anesthetic agents in experimental surgery aims at analgesia and restraining the animal, in order to achieve a reasonable degree of muscle relaxation and to produce sufficient analgesia. This practice requires the use of protocols for the administration of safe and efficient doses. Eight New Zealand rabbits were submitted to laparotomies demonstrating the surgical technique discipline of the local medical course. For pre-anesthetic medication, acepromazine 1 mg.kg-1 associated with ketamine 15 mg.kg-1 was used subcutaneously. Anesthesia was maintained with isoflurane and oxygen under a laryngeal mask in a Mapleson D anesthesia system and under spontaneous breathing. Hydration was performed with 10 ml.kg-1 saline every hour. A thermal mattress was used. Precordial stethoscope, pulse oximetry and clinical parameters were used for monitoring. For euthanasia, ketamine 10 mg.kg-1 associated with potassium chloride 19.1% 1 ml.kg-1 was used intravenously. The average weight of the rabbits was 2721.25 ± 275.01 grams and the duration of the anesthetic procedure was 120 ± 87 minutes. Discussion. In long-term anesthesia, such as laparotomies, the use of pre-anesthetic medication and then anesthetic induction by the combination of agents is recommended. However, anesthetic management requires monitoring to prevent insufficient or excessive doses from occurring.

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