Preventive Effects of Lecithinized Superoxide Dismutase and Methylprednisolone on Spinal Cord Injury in Rats: Transcriptional Regulation of Inflammatory and Neurotrophic Genes

Chikawa, Takashi; Ikata, Takaaki; Katoh, Shinsuke; Hamada, Yoshitaka; Kogure, Kentaro; Fukuzawa, Kenji

doi:10.1089/089771501750055802

Cited by 41 publications

(26 citation statements)

References 50 publications

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“…PC-SOD has been shown to protect endothelial cells in in vitro studies, 15,16 and it also has anti-inflammatory properties. 17 The results of the present study suggest that PC-SOD provides neuronal protection by antiapoptotic mechanisms. PC-SOD increased the mitochondrial levels of antiapoptotic Bcl-2 protein and decreased the subsequent cytosolic translocation of cytochrome c, thus attenuating the downstream caspase activation.…”

Section: Discussionsupporting

confidence: 52%

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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Section: Discussionsupporting

confidence: 52%

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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“…Therefore, it is worth noting in conclusion that a number of animal studies have suggested that PC-SOD is also effective in the treatment of these conditions (Tamagawa et al, 2000;Chikawa et al, 2001;Nakajima et al, 2001;den Hartog et al, 2004;Tsubokawa et al, 2007). Thus, the results obtained in this paper should provide useful evidence when considering the most appropriate clinical protocol for therapeutic administration of PC-SOD against these diseases.…”

Section: Pc-sod-and Dss-induced Colitis 161mentioning

confidence: 65%

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Ishihara¹,

Tanaka²,

Tasaka³

et al. 2008

J Pharmacol Exp Ther

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Ulcerative colitis (UC) involves intestinal mucosal damage induced by reactive oxygen species (ROS), in particular, superoxide anion. Superoxide dismutase (SOD) catalyzes dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) is a new modified form of SOD that has overcome previous clinical limitations of SOD. In this study, we examined the action of PC-SOD using an animal model of UC, dextran sulfate sodium (DSS)-induced colitis. DSS-induced colitis was ameliorated by daily intravenous administration of PC-SOD. Unmodified SOD produced a similar effect but only at more than 30 times the concentration of PC-SOD. In vivo electron spin resonance analysis confirmed that the increase in the colonic level of ROS associated with development of colitis was suppressed by PC-SOD administration. The dose-response profile of PC-SOD was bell-shaped, but simultaneous administration of catalase restored the ameliorative effect at high doses of PC-SOD. Accumulation of hydrogen peroxide was observed with the administration of high doses of PC-SOD, an effect that was suppressed by the simultaneous administration of catalase. We also found that either a weekly intravenous administration or daily oral administration of PC-SOD conferred protection. These results suggest that PC-SOD achieves its ameliorative effect against colitis through decreasing the colonic level of ROS and that its ineffectiveness at higher doses is because of the accumulation of hydrogen peroxide. Furthermore, we consider that intermittent or oral administration of PC-SOD can be applied clinically to improve the quality of life of UC patients.

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“…MPSS did not reduce astrogliosis. Studies have shown that MPSS inhibits the expressions of several cytokines (46,47).…”

Section: Discussionmentioning

confidence: 99%

“…This therapy is based on reported improvements in neurological recovery in humans and laboratory animals (7,13,14,52,51) and by its reduction in early pathophysiological events and macrophage infiltration (46,53,54 The effects of MPSS on spinal cord injury may depend on the dose, the timing of treatment, the duration of treatment, and the spinal cord injury model used (55). Although MPSS has been shown to reduce the expression of inflammatory cytokines, downregulate lipid peroxidation in the spinal cord and reduce the density of ED-I-positive macrophages or/and microglia at the first 2 days after contusion (46,56), significant functional recovery associated with these biochemical or histological changes was not observed.…”

Section: Discussionmentioning

confidence: 99%

Ait-082 and Methylprednisolone Singly, but Not in Combination, Enhance Functional and Histological Improvement after Acute Spinal Cord Injury in Rats

Jiang

Khan²,

Pj³

et al. 2004

Int J Immunopathol Pharmacol

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Extracellular non-adenine based purines are neuroprotective. Preliminary studies indicate that administration of the synthetic purine 4–[[3–(1,6 dihydro-6-oxo-9- purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to rats immediately after acute spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11–12 spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis. AIT-082 administrations significantly reduced locomotor impairment from 1–21 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and astrogliosis at the injured cords but did not alter the extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced hemorrhage and the number of macrophages and/or microglia, but did not alter astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and astrogliosis). In contrast, administration of AIT-082 and MPSS together abolished the beneficial effects observed when either drug was given individually. These results suggest that MPSS and AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.

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Preventive Effects of Lecithinized Superoxide Dismutase and Methylprednisolone on Spinal Cord Injury in Rats: Transcriptional Regulation of Inflammatory and Neurotrophic Genes

Cited by 41 publications

References 50 publications

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

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

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Ait-082 and Methylprednisolone Singly, but Not in Combination, Enhance Functional and Histological Improvement after Acute Spinal Cord Injury in Rats

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