Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production

Takenaga, Mitsuko; Ohta, Yuki; Tokura, Yukie; Hamaguchi, Akemi; Nakamura, Masaya; Igarashi, Rie

doi:10.1016/j.jconrel.2005.10.022

Cited by 40 publications

(22 citation statements)

References 24 publications

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“…However, the low stability of Cu/Zn-SOD in plasma and its low affinity for cells form an obstacle for its clinical development. PC-SOD, a derivative of SOD with higher stability in plasma and higher affinity for tissue, thus offers an attractive alternative to Cu/Zn-SOD, and its heightened therapeutic actions were demonstrated in animal models of various inflammatory diseases such as idiopathic pulmonary fibrosis (IPF), colitis, focal cerebral ischemic injury, and spinal cord injury-induced motor dysfunction (20,37,38,40). In a phase I clinical study, intravenously administered PC-SOD (40 -160 mg) had a terminal half-life of more than 24 h, with good safety and tolerability (7,35).…”

Section: Discussionmentioning

confidence: 99%

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice

Tanaka

Sato

Aoshiba

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.

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Section: Discussionmentioning

confidence: 99%

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice

Tanaka

Sato

Aoshiba

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It would be interesting to study whether PC-SOD affects upstream cell-survival targets, such as PI3K/AKT and HIF-1. 2,7,23 Recently, lecithinized SOD has also been used in human subjects for corneal ulcers. 24 PC-SOD is a promising therapeutic option against cerebral stroke, as it may simultaneously modulate molecular targets activated in ischemia, oxidative stress, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Protective effects of PC-SOD have been reported in spinal cord and traumatic brain injuries. [7][8][9] However, a potential protective role for PC-SOD in cerebral ischemic injuries has not been addressed before. Therefore, the present study was designed to study whether PC-SOD protects against neuronal apoptotic cell death in a rat model of transient focal ischemia.…”

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confidence: 99%

Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats

Tsubokawa

Jadhav

Solaroğlu

et al. 2007

Stroke

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Background and Purpose-Recent studies have shown the antiapoptotic neuroprotective effects of lecithinized superoxide dismutase (PC-SOD) in different forms of brain injury. We tested the effects of PC-SOD in focal cerebral ischemia in the rat middle cerebral artery occlusion model (MCAO). Methods-Adult male Sprague-Dawley rats were treated with PC-SOD (0.3, 1.0, and 3.0 mg/kg) administered intravenously after 90 minutes of occlusion (beginning of reperfusion). Physiological parameters, neurological score, and infarct volume were assessed at 24 and 72 hours in 3 groups of animals: sham-operated (nϭ18), MCAO treated with vehicle (nϭ26), and MCAO treated with PC-SOD (nϭ37). Oxidative stress was evaluated by malondialdehyde assay, and the apoptotic mechanisms were studied by Western blotting. Results-PC-SOD treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. PC-SOD treatment decreased malondialdehyde levels, cytochrome c, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression. Conclusions-Inhibition of oxidative stress with PC-SOD treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms.

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“…The room had a 12 h light/dark cycle. The study protocol was approved by the An- Spinal Cord Injury and Drug Treatment Impact injury of the spinal cord was induced by using the weight-drop device developed at New York University (NYU impact model), according to the method described by Takenaga et al 26,27) and Kitagawa et al 28) Adult female SD rats weighing 210-230 g were anesthetized and dorsal laminectomy was performed at the T 10 level, after which a 10 g weight was dropped onto the spinal cord from a height of 25 mm.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Am-80, a Synthetic Retinoid, on Spinal Cord Injury-Induced Motor Dysfunction in Rats

Takenaga

Ohta

Tokura

et al. 2009

Biological & Pharmaceutical Bulletin

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Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production

Cited by 40 publications

References 24 publications

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice

Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats

The Effect of Am-80, a Synthetic Retinoid, on Spinal Cord Injury-Induced Motor Dysfunction in Rats

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