ArticleInternational journal of molecular sciences2022
Hypothermia Alleviates Reductive Stress, a Root Cause of Ischemia Reperfusion Injury.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Pooled it
- The Association Between Early Postoperative Temperature Trajectories and Severe Acute Kidney Injury After Valvular Heart Surgery: A Retrospective Cohort Study.Journal of clinical medicine · 2026Article
- Nanotechnology for ischemic stroke treatment: addressing challenges across stroke management stages.Frontiers in molecular biosciences · 2026Review
- Ozone protects against ischemia-reperfusion injury: molecular mechanisms.Frontiers in pharmacology · 2026Review
- Pubovesical Complex-Sparing Under Hypothermia During Robotic-Assisted Laparoscopic Radical Prostatectomy: A Single-Institution Case Series.Journal of clinical medicine · 2025Article
- Revisiting optimal static lung preservation techniques in an era when machine perfusion is transforming organ recovery: thermoregulation is still an important concept.Journal of thoracic disease · 2025Review
- Preoptic activation induces a torpor-like hypothermic and hypometabolic state that is cerebroprotective.bioRxiv : the preprint server for biology · 2025Article
- Potential of CBD Acting on Cannabinoid Receptors CBInternational journal of molecular sciences · 2024Review
- Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury.Biomedicines · 2024Review
- Oxygen is toxic in the cold inFrontiers in physiology · 2024Article
- VHL-deficiency leads to reductive stress in renal cells.Free radical biology & medicine · 2023Article
- Molecular Frontiers in Transplantation-Induced Ischemia-Reperfusion Injury.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Ischemia reperfusion injury is common in transplantation. Previous studies have shown that cooling can protect against hypoxic injury. To date, the protective effects of hypothermia have been largely associated with metabolic suppression. Since kidney transplantation is one of the most common organ transplant surgeries, we used human-derived renal proximal tubular cells (HKC8 cell line) as a model of normal renal cells. We performed a temperature titration curve from 37 °C to 22 °C and evaluated cellular respiration and molecular mechanisms that can counteract the build-up of reducing equivalents in hypoxic conditions. We show that the protective effects of hypothermia are likely to stem both from metabolic suppression (inhibitory component) and augmentation of stress tolerance (activating component), with the highest overlap between activating and suppressing mechanisms emerging in the window of mild hypothermia (32 °C). Hypothermia decreased hypoxia-induced rise in the extracellular lactate:pyruvate ratio, increased ATP/ADP ratio and mitochondrial content, normalized lipid content, and improved the recovery of respiration after anoxia. Importantly, it was observed that in contrast to mild hypothermia, moderate and deep hypothermia interfere with HIF1 (hypoxia inducible factor 1)-dependent HRE (hypoxia response element) induction in hypoxia. This work also demonstrates that hypothermia alleviates reductive stress, a conceptually novel and largely overlooked phenomenon at the root of ischemia reperfusion injury.
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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.