scholarly journals Drug-Induced Mitochondrial Toxicity in the Geriatric Population: Challenges and Future Directions

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Yvonne Will ◽  
Jefry E. Shields ◽  
Kendall B. Wallace
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mitochondrial Function ◽  
Lifestyle Changes ◽  
Patient Treatment ◽  
Mitochondrial Toxicity ◽  
Drug Induced ◽  
Geriatric Population ◽  
Drug Classes ◽  
Age Related

Mitochondrial function declines with age, leading to a variety of age-related diseases (metabolic, central nervous system-related, cancer, etc.) and medication usage increases with age due to the increase in diseases. Drug-induced mitochondrial toxicity has been described for many different drug classes and can lead to liver, muscle, kidney and central nervous system injury and, in rare cases, to death. Many of the most prescribed medications in the geriatric population carry mitochondrial liabilities. We have demonstrated that, over the past decade, each class of drugs that demonstrated mitochondrial toxicity contained drugs with both more and less adverse effects on mitochondria. As patient treatment is often essential, we suggest using medication(s) with the best safety profile and the avoidance of concurrent usage of multiple medications that carry mitochondrial liabilities. In addition, we also recommend lifestyle changes to further improve one’s mitochondrial function, such as weight loss, exercise and nutrition.

scholarly journals Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

AGE ◽  
2012 ◽  
Vol 35 (2) ◽  
pp. 331-342 ◽  
Author(s):  
Elisa Mitiko Kawamoto ◽  
Andrea Rodrigues Vasconcelos ◽  
Sabrina Degaspari ◽  
Ana Elisa Böhmer ◽  
Cristoforo Scavone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Cyclic Gmp ◽  
Oxidative Status ◽  
Age Related ◽  
Age Related Changes

scholarly journals Acute Graft-Versus-Host Disease, Infections, Vascular Events and Drug Toxicities Affecting the Central Nervous System

2021 ◽  
Vol 12 ◽  
Author(s):  
Janaki Manoja Vinnakota ◽  
Robert Zeiser
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Neurological Deficits ◽  
Vascular Events ◽  
Drug Induced ◽  
Curative Therapy ◽  
The Central Nervous System ◽  
Acute Graft

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for patients with hematological malignancies. Acute Graft versus host diseases (GVHD) is a major immune mediated side effect of allo-HCT that can affect the central nervous system (CNS) in addition to post-allo-HCT vascular events, drug toxicity or infections. Here we summarize and discuss recent preclinical data on the CNS as a target of acute GVHD and the known mechanisms contributing to neurotoxicity with a focus on microglia and T cells. We also discuss open questions in the field and place the findings made in mouse models in a clinical context. While in mice the neurological deficits can be assessed in a controlled fashion, in patients the etiology of the CNS damage is difficult to attribute to acute GVHD versus infections, vascular events, and drug-induced toxicity. Ultimately, we discuss novel therapies for GVHD of the CNS. Our understanding of the biological mechanisms that lead to neurotoxicity after allo-HCT increased over the last decade. This review provides insights into CNS manifestations of GVHD versus other etiologies of CNS damage in mice and patients.

scholarly journals Impact of pharmacological agents on mitochondrial function: a growing opportunity?

2019 ◽  
Vol 47 (6) ◽  
pp. 1757-1772 ◽  
Author(s):  
Megan L. Stoker ◽  
Emma Newport ◽  
James C. Hulit ◽  
A. Phillip West ◽  
Karl J. Morten
Keyword(s):  
Side Effects ◽  
Mitochondrial Function ◽  
Immune Modulation ◽  
Antiviral Agents ◽  
Aging Population ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Beneficial Effects ◽  
Drug Classes ◽  
Target Effects

Present-day drug therapies provide clear beneficial effects as many diseases can be driven into remission and the symptoms of others can be efficiently managed; however, the success of many drugs is limited due to both patient non-compliance and adverse off-target or toxicity-induced effects. There is emerging evidence that many of these side effects are caused by drug-induced impairment of mitochondrial function and eventual mitochondrial dysfunction. It is imperative to understand how and why drug-induced side effects occur and how mitochondrial function is affected. In an aging population, age-associated drug toxicity is another key area of focus as the majority of patients on medication are older. Therefore, with an aging population possessing subtle or even more dramatic individual differences in mitochondrial function, there is a growing necessity to identify and understand early on potentially significant drug-associated off-target effects and toxicity issues. This will not only reduce the number of unwanted side effects linked to mitochondrial toxicity but also identify useful mitochondrial-modulating agents. Mechanistically, many successful drug classes including diabetic treatments, antibiotics, chemotherapies and antiviral agents have been linked to mitochondrial targeted effects. This is a growing area, with research to repurpose current medications affecting mitochondrial function being assessed in cancer, the immune system and neurodegenerative disorders including Parkinson's disease. Here, we review the effects that pharmacological agents have on mitochondrial function and explore the opportunities from these effects as potential disease treatments. Our focus will be on cancer treatment and immune modulation.

scholarly journals IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS

1972 ◽  
Vol 135 (4) ◽  
pp. 874-889 ◽  
Author(s):  
Donald H. Gilden ◽  
Gerald A. Cole ◽  
Neal Nathanson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Antigen ◽  
Central Nervous System Disease ◽  
Lymphocytic Choriomeningitis ◽  
Lymphoid Cells ◽  
Intracerebral Injection ◽  
Spleen Cells ◽  
Drug Induced ◽  
Immune Spleen Cells

Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors. Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice. Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease. It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers. Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.

Effect of Antagonism at Central Nervous System M3 Muscarinic Receptors on Laryngeal Chemoresponse

1997 ◽  
Vol 106 (11) ◽  
pp. 920-926 ◽  
Author(s):  
Brent E. Richardson ◽  
Kerri J. Pernell ◽  
George S. Goding
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Messenger Rna ◽  
Sudden Infant ◽  
Respiratory Drive ◽  
Age Related ◽  
M3 Receptors ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

The laryngeal chemoresponse (LCR), comprising laryngeal adductor spasm, central apnea, and subsequent cardiovascular instability, is thought to be a factor in sudden infant death syndrome. A muscarinic subtype receptor, M3, appears to be involved in central respiratory drive and control. Both the duration of the LCR apnea and levels of M3 receptor messenger RNA in the brain stem change according to postnatal age. This study examined the effect of central nervous system antagonism at M3 receptors on the LCR with respect to animal age and dose of antagonist. Ten piglets in each of three age groups (group 1, 5 to 8 days; group 2, 18 to 21 days; and group 3, 40 to 43 days) received a series of four increasing doses of an M3 antagonist ( p-fluoro-hexahydro-siladiphenidol) by intracerebral ventricle injection. The LCR was evoked at baseline and after each dose of antagonist. An effect on susceptible animals (groups 1 and 2) was evident by the second antagonist dose, and persisted for the remainder of the experiment (2 hours). At completion of the experiment, mean apnea duration had decreased in group 1 (61%, p < .05), and group 2 (57%, p < .05), but was unchanged in group 3 (<10%, p not significant). Length of mean baseline apneas correlated directly with degree of apnea shortening. The reduction is not attributable to changes in arterial Po2 or Pco2 or baseline respiratory rate. These results support an age-related influence on the LCR by M3 receptors in younger animals that decreases with maturation.

scholarly journals Changes in blood circulation and the central nervous system functions in 4–10 year children with visual impairment

2021 ◽  
Vol 100 (3) ◽  
pp. 261-267
Author(s):  
Tatyana V. Popova ◽  
Elena G. Kokoreva ◽  
Olga G. Kourova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Visual Impairment ◽  
Blood Circulation ◽  
Visual Impairments ◽  
Heart Rhythm ◽  
Stress Index ◽  
Healthy Children ◽  
Age Related ◽  
Psychophysiological Functions

Introduction. Visual impairment is the most common disturbances during the child development in preschool and primary school age. Such children need care with the health-improving technology based on scientific knowledge about the characteristics of their psychophysiological functions. The aim of the study is to identify development-related changes in blood circulation and central nervous system functions in 4-10 year healthy children and cases with visual impairments. Materials and methods. A total of 380 children were examined by electrocardiography, electroencephalography, registration of neurodynamic processes, analysis of the tactile function, and self-assessment of anxiety. Results. In subjects with visual impairment, an increase in age-related heterochronism in the development of psychophysiological functions was revealed. The accuracy indices of time intervals and tactile sensitivity of the skin of the fingers were higher, and the indices of physical development, kinematometry, and mobility of nervous processes in many age groups are lower than in healthy ones. Such adaptive changes were accompanied by an increase in functional stress. So, for example, in preschool children from 4 to 6 years, when analyzing the structure of the heart rhythm, an increase in the values of the stress index was noted (from 148.08 ± 3.32 to 220.08 ± 3.62 c.u.; p < 0.05). Conclusion. Judging by the high values of activity indices of the central mechanisms of heart rhythm regulation, anxiety, and the nature of bioelectric changes on the EEG, the “price” of age-related adaptation in children with sensory impairments rises. It contributes to the development of disadaptation. The conclusion is made about the need to develop effective means of psychophysical correction of children with visual impairments, taking into account the nature of age-related changes.

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