Effect of Lecithinized-Superoxide Dismutase on the Rat Colitis Model Induced by Dextran Sulfate Sodium.

Hori, Yusuke; Hoshino, Jiro; Yamazaki, C.; Sekiguchi, Tomoko; Miyauchi, Satoshi; Mizuno, Syoji; Horie, Katsuyuki

doi:10.1254/jjp.74.99

Cited by 16 publications

(10 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A, PC-SOD produced the maximum beneficial effect at 1.5 to 3 kU/kg, whereas higher doses (6 -12 kU/kg) had no significant effect on DAI. A similar bell-shaped profile has also been reported in a rat model of DSS-induced colitis (Hori et al, 1997). In the case of colon shortening and colonic MPO activation, the maximal effect was again observed in response to 1.5 to 3 kU/kg PC-SOD (Fig.…”

Section: A Comparison Of the Effect Of Pc-sod And U-sod On Dss-inducesupporting

confidence: 82%

“…In phase I clinical studies, intravenously administered PC-SOD (40 -160 mg) had a terminal half-life of more than 24 h, with good safety and tolerability (Broeyer et al, 2008;Suzuki et al, 2008a). Furthermore, intravenously administered PC-SOD ameliorated dextran sulfate sodium (DSS)-induced colitis in rats, an IBD-related colitis animal model (Hori et al, 1997), suggesting that PC-SOD is effective for the treatment of IBD patients. In fact, recent published results of phase II clinical study have shown that intravenously administered PC-SOD (40 or 80 mg) significantly improved the disease activity index (DAI) scores of UC patients (Suzuki et al, 2008b).…”

mentioning

confidence: 99%

“…However, the comparison of PC-SOD with unmodified SOD (U-SOD) based on pharmacological activity against colitis has not been undertaken, and a decrease in the ROS level with PC-SOD administration has not been demonstrated in vivo. In addition to U-SOD, a bell-shaped dose-response profile of PC-SOD has been reported for various pharmacological activities, including anticolitis activity (Mao et al, 1993;Hori et al, 1997;Tamagawa et al, 2000;Tsubokawa et al, 2007). However, its underlying mechanism has remained unknown.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Ishihara¹,

Tanaka²,

Tasaka³

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

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.

show abstract

Section: A Comparison Of the Effect Of Pc-sod And U-sod On Dss-inducesupporting

confidence: 82%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Ishihara¹,

Tanaka²,

Tasaka³

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In this study, we used PC-SOD, a derivative of SOD with higher stability in plasma and a higher affinity for tissue, which shows greater therapeutic effects than SOD in animal models of various inflammatory diseases, such as IPF, colitis, focal cerebral ischemic injury, and spinal cord injury-induced motor dysfunction (Hori et al, 1997;Tamagawa et al, 2000;Ishihara et al, 2009;Tanaka et al, 2010). We have clearly shown that PC-SOD ameliorates pulmonary emphysema.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Lecithinized Superoxide Dismutase on Pulmonary Emphysema

Tanaka

Tanaka²,

Miyazaki³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

No medication exists that clearly improves the mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions, play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn-SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leukocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema, and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of proinflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smokeinduced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in the inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.

show abstract

“…Furthermore, it also reduced the increase of WBC, which is a characteristic of the acute fulminating type of ulcerative colitis. In a recent study, we suggested that an allergic-like reaction occurred in this model because neutrophils and eosinophils infiltrated the colonic mucosa (8). Bleeding was observed in the area of erosion.…”

Section: Discussionmentioning

confidence: 66%

Effects of Chondroitin Sulfate on Colitis Induced by Dextran Sulfate Sodium in Rats

Hori

Hoshino

Yamazaki

et al. 2001

Japanese Journal of Pharmacology

Self Cite

View full text Add to dashboard Cite

ABSTRACT-Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg / kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/ kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.

show abstract

Effect of Lecithinized-Superoxide Dismutase on the Rat Colitis Model Induced by Dextran Sulfate Sodium.

Cited by 16 publications

References 12 publications

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis

Therapeutic Effect of Lecithinized Superoxide Dismutase on Pulmonary Emphysema

Effects of Chondroitin Sulfate on Colitis Induced by Dextran Sulfate Sodium in Rats

Contact Info

Product

Resources

About