ArticleChemical research in toxicology2010
Immunosuppressant neurotoxicity in rat brain models: oxidative stress and cellular metabolism.
Article in Chemical research in toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Effect of dietary sodium restriction on human urinary metabolomic profiles.Clinical journal of the American Society of Nephrology : CJASN · 2015Trial
- Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.PloS one · 2011Trial
- Dynamic evolution of brain structural patterns in liver transplantation recipients: a longitudinal study based on 3D convolutional neuronal network model.European radiology · 2023Article
- Cognitive Outcome After Islet Transplantation.Transplantation direct · 2023Article
- Cardiovascular effects of immunosuppression agents.Frontiers in cardiovascular medicine · 2022Review
- Immunosuppression-related neurological disorders in kidney transplantation.Journal of nephrology · 2021Review
- Epileptic Seizures After Allogeneic Hematopoietic Stem Cell Transplantation.Frontiers in neurology · 2021Review
- Article
- Mechanistic Target of Rapamycin Pathway in Epileptic Disorders.Journal of Korean Neurosurgical Society · 2019Article
- Calcineurin signaling as a target for the treatment of alcohol abuse and neuroinflammatory disorders.Progress in molecular biology and translational science · 2019Review
- Cerebral metabolite alterations in patients with posttransplant encephalopathy after liver transplantation.PloS one · 2019Article
- Cellular antiseizure mechanisms of everolimus in pediatric tuberous sclerosis complex, cortical dysplasia, and non-mTOR-mediated etiologies.Epilepsia open · 2018Article
- Kidney Fibrosis: Origins and Interventions.Transplantation · 2017Review
- The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases.Journal of aging research · 2016Review
- Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex.Neuro-oncology · 2015Review
- Oxidative and Nitrosative Stress in Stable Renal Transplant Recipients with Respect to the Immunosuppression Protocol - Differences or Similarities?Journal of medical biochemistry · 2015Article
- Everolimus and sirolimus in transplantation-related but different.Expert opinion on drug safety · 2015Review
- Altered metabolomic profiles may be associated with sevoflurane-induced neurotoxicity in neonatal rats.Neurochemical research · 2015Article
- Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Coadministration of the calcineurin inhibitor cyclosporine (CsA) and the mTOR inhibitors sirolimus (SRL) or everolimus (RAD) increases the efficacy of immunosuppression after organ transplantation. Neurotoxicity of CsA is a major clinical problem. Our goal was to assess the effects of CsA, SRL, and RAD on brain cell metabolism. The studies included the comparison of immunosuppressant-mediated effects on glucose metabolism, energy production, and reactive oxygen species (ROS) formation in perfused rat brain slices, primary rat astrocytes, and C6 glioma cells. In brain slices and astrocytes, CsA inhibited Krebs cycle metabolism, while activating anaerobic glycolysis, most likely to compensate for the inhibition of mitochondrial energy production. SRL and RAD inhibited cytosolic glycolysis but did not cause changes in mitochondrial energy production. CsA + SRL inhibited Krebs cycle and glycolysis, thus reducing the ability of the cell to compensate for the negative effects of CsA on mitochondrial nucleoside triphosphate synthesis. In contrast to SRL at the concentrations tested, RAD reduced the CsA-induced ROS formation and antagonized CsA-induced effects on glucose and energy metabolism. Surprisingly, in C6 cells, SRL and RAD exposure resulted in high ROS concentrations without significant impairment of cell metabolism. Our results suggested that SRL enhances CsA-induced ROS formation and negative metabolic effects in brain cells, while RAD seems to antagonize the CsA effects. However, the three models showed different metabolic responses when challenged with the study drugs. In contrast to SRL, RAD enhances ROS formation in C6 glioma cells but has only minor effects on normal rat brain tissue.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.