Free radical scavenging and antioxidant effects of lactate ion: an in vitro study

Groussard, Carole; Morel, Isabelle; Chevanne, Martine; Monnier, M.; Cillard, Josiane; Delamarche, Arlette

doi:10.1152/jappl.2000.89.1.169

Cited by 205 publications

(120 citation statements)

References 25 publications

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“…Hypoxia is well known to induce radiation resistance, because free radical-induced DNA damage requires oxygen molecules [41]. Lactate is produced by anaerobic glycolysis and may scavenge superoxide and hydroxyl radicals [42].…”

Section: Discussionmentioning

confidence: 99%

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Toyonaga

Yamaguchi

Hirata

et al. 2016

Eur J Nucl Med Mol Imaging

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The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. 4Results:All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p=0.007, p=0.04, and p=0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p=0.0028, p=0.037, and p=0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky Performance Scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. Conclusions:We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically-active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

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Section: Discussionmentioning

confidence: 99%

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Toyonaga

Yamaguchi

Hirata

et al. 2016

Eur J Nucl Med Mol Imaging

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“…This lactateassociated radioresistance was hypoxia independent, that is, well-oxygenated high-lactate tumors were radioresistant as well (24). Lactate is able to scavenge superoxide and hydroxyl radicals in vitro (74). Monocarboxylate transporters (MCT) are involved in lactate transport.…”

Section: Tumor Glucose Metabolism and Radioresistancementioning

confidence: 99%

Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy

Meijer

Kaanders

Span

et al. 2012

Clinical Cancer Research

383

344

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Radiotherapy, an important treatment modality in oncology, kills cells through induction of oxidative stress. However, malignant tumors vary in their response to irradiation as a consequence of resistance mechanisms taking place at the molecular level. It is important to understand these mechanisms of radioresistance, as counteracting them may improve the efficacy of radiotherapy. In this review, we describe how the hypoxia-inducible factor 1 (HIF-1) pathway has a profound effect on the response to radiotherapy. The main focus will be on HIF-1-controlled protection of the vasculature postirradiation and on HIF-1 regulation of glycolysis and the pentose phosphate pathway. This aberrant cellular metabolism increases the antioxidant capacity of tumors, thereby countering the oxidative stress caused by irradiation. From the results of translational studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and sensitizes various solid tumors to irradiation. Clin Cancer Res; 18(20); 5585-94. Ó2012 AACR.

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“…Availability of O 2 is still adequate for oxidative phosphorylation; however, the presence of lactate simulates conditions that may be recognised as hypoxic in nature, influencing angiogenesis, oxidative defence mechanisms and collagen synthesis, all serving to improve muscle function. Lactate has also previously been suggested to act as a A. Philp, A. L. Macdonald and P. W. Watt 4570 scavenger for free radicals released into the circulation (Groussard et al, 2000) and could potentially operate in this manner as exercise intensity increases.…”

Section: Lactate and Painmentioning

confidence: 99%

Lactate – a signal coordinating cell and systemic function

Philp¹,

Macdonald

Watt³

2005

Journal of Experimental Biology

265

177

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SUMMARY Since its first documented observation in exhausted animal muscle in the early 19th century, the role of lactate (lactic acid) has fascinated muscle physiologists and biochemists. Initial interpretation was that lactate appeared as a waste product and was responsible in some way for exhaustion during exercise. Recent evidence, and new lines of investigation, now place lactate as an active metabolite, capable of moving between cells, tissues and organs, where it may be oxidised as a fuel or reconverted to form pyruvate or glucose. The questions now to be asked concern the effects of lactate at the systemic and cellular level on metabolic processes. Does lactate act as a metabolic signal to specific tissues, becoming a metabolite pseudo-hormone?Does lactate have a role in whole-body coordination of sympathetic/parasympathetic nerve system control? And, finally, does lactate play a role in maintaining muscle excitability during intense muscle contraction? The concept of lactate acting as a signalling compound is a relatively new hypothesis stemming from a combination of comparative, cell and whole-organism investigations. It has been clearly demonstrated that lactate is capable of entering cells via the monocarboxylate transporter (MCT) protein shuttle system and that conversion of lactate to and from pyruvate is governed by specific lactate dehydrogenase isoforms, thereby forming a highly adaptable metabolic intermediate system. This review is structured in three sections,the first covering pertinent topics in lactate's history that led to the model of lactate as a waste product. The second section will discuss the potential of lactate as a signalling compound, and the third section will identify ways in which such a hypothesis might be investigated. In examining the history of lactate research, it appears that periods have occurred when advances in scientific techniques allowed investigation of this metabolite to expand. Similar to developments made first in the 1920s and then in the 1980s, contemporary advances in stable isotope, gene microarray and RNA interference technologies may allow the next stage of understanding of the role of this compound, so that, finally, the fundamental questions of lactate's role in whole-body and localised muscle function may be answered.

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Free radical scavenging and antioxidant effects of lactate ion: an in vitro study

Cited by 205 publications

References 25 publications

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy

Lactate – a signal coordinating cell and systemic function

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