Elsevier

Neuroscience

Volume 62, Issue 2, September 1994, Pages 399-406
Neuroscience

The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury

https://doi.org/10.1016/0306-4522(94)90375-1Get rights and content

Abstract

Pyrroloquinoline quinone is a ubiquitous redox cofactor and putative essential nutrient in mammals. Pyrroloquinoline quinone has recently been demonstrated to depress N-methyl-d-rasparate induced electrical responses and is neuroprotective in vitro. In addition, pyrroloquinoline quinone has been demonstrated to act as a free radical scavenger in mammalian tissues. In this study, we demonstrate a neuroprotective effect of pyrroloquinoline quinone in an in vivo cerebral hypoxia/ischemia model in the rodent. Significant reduction in infarct size resulted from pyrroloquinoline quinone pretreatment and also when pyrroloquinoline quinone was administered following induction of hypoxia/ischemia. The neuroprotective effect was not dependent on change in core or cranial temperatures, as there was no difference between temperature measurements in pyrroloquinoline quinone-treated and vehicle-treated controls. No changes in electroencephalographie activity were observed at neuroprotective doses. These findings suggest that pyrroloquinoline quinone may represent a novel class of quinoid reagents of potential use in the treatment of neurological disorders that involve excitotoxicity.

This study demonstrates a protective effect of the novel essential nutrient pyrroloquinoline quinone on brain injury in a rodent model of cerebral hypoxia/ischemia. Pyrroloquinoline quinone was neuroprotective when administered before and even after the insult, and did not appear to have significant neurobehavioral side effects. Pyrroloquinoline quinone represents a new class of agents with potential use in the therapy of stroke.

Reference (58)

  • KumazawaT. et al.

    Trace levels of pyrroloquinoline quinone in human and rat samples detected by gas chromatography/mass spectrometry

    Biochem. biophys. Acta

    (1992)
  • MajewskaM.D. et al.

    Regulation of the NMDA receptor by redox phenomena: inhibitory role ofascorbate

    Brain Res.

    (1990)
  • McDonaldJ.W. et al.

    Systemic administration of MK-801 protects against W-methyl-D-aspartate- and quisqualate-mediated neurotoxicity in perinatal rats

    Neuroscience

    (1990)
  • MeldrumB. et al.

    Excitatory amino acid neurotoxicity and neurodegenerative disease

    Trends pharmac. Sci.

    (1990)
  • PazM.A. et al.

    Specific detection of quinoproteins by redox-cycling staining

    J. biol. Chem.

    (1991)
  • PazM.A. et al.

    The amplified detection of free and bound methoxatin (PQQ) with nitroblue tetrazolium redox reactions: insights into the PQQ-locus

    Biochem. biophys. Res. Commun

    (1988)
  • RadiR. et al.

    Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of Superoxide and nitric oxide

    Arch. Biochem. Biophys.

    (1991)
  • RadiR. et al.

    Peroxynitrite oxidation ofsulfhydryls

    J. biol Chem

    (1991)
  • ReganR.F. et al.

    NMDA neurotoxicity in murine cortical cell cultures is not attenuated by hemoglobin or inhibition of nitric oxide synthesis

    Neurosci. Lett.

    (1993)
  • XuF. et al.

    Pyrroloquinoline quinone acts with flavin reductase to reduce ferryl myoglobin in vitro and protects isolated heart from re-oxygenation injury

    Bioehem. biophys. Res. Commun.

    (1993)
  • AdachiO. et al.

    Adult formation of pyrroloquinoline quinone and amino acid

    Biofactors

    (1988)
  • AizenmanE. et al.

    Interaction of the putative essential nutrient pyrroloquinoline quinone with the N-methyl-d-asparate receptor redox modulatory site

    J. Neurosci.

    (1992)
  • AizenmanE. et al.

    Further evidence that PQQ interacts with the NMDA receptor redox modulatory site

    Soc. Neurosci. Abstr.

    (1993)
  • BeckmanJ.S. et al.

    Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and Superoxide

  • BuchanA. et al.

    Hypothermia but not the W-methyl-D-aspartate antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia

    J. Neurosci.

    (1990)
  • ChoiD.W. et al.

    The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death

    A. Rev. Neurosci.

    (1990)
  • ChoiY.-B. et al.

    Neuroprotection ofPQQ involves scavenging of Superoxide anions

    Soc. Neurosci. Abstr.

    (1993)
  • ClemensJ.A. et al.

    LY178002 reduces rat brain damage after transient global forebrain ischemia

    Stroke

    (1991)
  • DawsonV.L. et al.

    Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures

    J. Neurosci.

    (1993)
  • Cited by (67)

    • Adverse effect of superoxide-induced mitochondrial damage in granulosa cells on follicular development in mouse ovaries

      2021, Free Radical Biology and Medicine
      Citation Excerpt :

      In our previous study using boar sperm, the redox activities of PQQ that kept both integrity of mitochondria DNA and stability of proteins involved in transcription and translation systems in mitochondria were much higher than those of coenzyme Q10 [35]. Moreover, the positive effects of PQQ were also observed in in vivo, such as tissue injury by hypoxic [36], liver damage via oxidative stress [37] or the depletion of glutathione in the embryo [38], indicating that PQQ would improve survivability and quality of granulosa cells. However, the effects of PQQ on follicular development remained unclear.

    • Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer's disease

      2017, Heliyon
      Citation Excerpt :

      PQQ is considered to be an important nutrient having anti-inflammatory, antioxidative and neuroprotective effects [21, 22]. In animals models, PQQ attenuates neuronal cell death associated with stroke, spinal cord injury and traumatic brain injury [33, 34], by decreasing iNOs expression, protecting NMDA receptor function, decreasing lesion or infarct size and increasing axon density [35, 36]. In neural stem and progenitor cells, PQQ increases the antioxidant enzymes SOD, catalase and glutathione peroxidase [37].

    • Overexpression of pyrroloquinoline quinone biosynthetic genes affects l-sorbose production in Gluconobacter oxydans WSH-003

      2016, Biochemical Engineering Journal
      Citation Excerpt :

      Besides its vital functions in the production of many important bulk chemicals [3], PQQ has attracted considerable attention due to its positive physiological effects on growth and development of mammals [6,7]. PQQ has also been recognized as a neuro-protective factor in a rodent model of hypoxic brain injury [8,9], and therefore qualifies as a newcomer to the B group of vitamins [10]. About twenty years ago, Gupta et al. found that the deficiency of pqqE on the genome of G. oxydans IFO 3293 coincided with a deficiency in quinoprotein glucose dehydrogenase activity [11].

    • Excitation-Inhibition Epilepsies

      2013, Neural Circuit Development and Function in the Healthy and Diseased Brain: Comprehensive Developmental Neuroscience
    View all citing articles on Scopus
    View full text