The role of nitric oxide synthase in dextran sulfate sodium (DSS) colitis

1995 ◽  
Vol 108 (4) ◽  
pp. A937 ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 5 ◽  
Author(s):  
Jing Zhang ◽  
Qin Li ◽  
Yang Wei ◽  
Xingyao Long ◽  
Jianfei Mu ◽  
...  

Shuidouchi is a traditionally fermented soybean product in China. Shuidouchi production requires a variety of processes; however, the production process has not been standardized. It can be developed into high-quality products with enhanced health effects by improving the design of its fermentation process and increasing the content of its active ingredients. In this study, a single-factor experiment was conducted that established different process conditions to determine the fermentation conditions that achieve the highest content of active ingredients and the best in vitro antioxidant effect. The effect of Shuidouchi on the prevention of dextran sulfate sodium-induced colitis in mice was also observed. The obtained results indicated that the optimal process conditions involved soaking for 12 h, placement in a glass container, and fermentation at 35 °C for 48 h. Shuidouchi that was fermented under such conditions had the highest level of soybean isoflavones and exerted greater antioxidant effects than if fermented under other conditions. The Shuidouchi extract (soaking twice the quantity of water for 12 h, placing in a glass container, and fermenting at 35 °C for 48 h) obtained by using the optimal fermentation process can prevent the shortening of the colon and increase the weight-to-length ratio of the colon that is caused by colitis. Shuidouchi extraction not only effectively reduces the disease activity index and the levels of serum endothelin (ET), substance P (SP), and interleukin-10 (IL-10), it also increases the levels of somatostatin (SS), vasoactive intestinal peptide (VIP), and interleukin-2 (IL-2) of mice with colitis. In addition, Shuidouchi extraction increased the levels of glutathione (GSH) and superoxide dismutase (SOD) in colitis mice; in contrast, Shuidouchi decreased the levels of myeloperoxidase (MPO) and malondialdehyde (MDA) in the colon of mice with colitis. Further detection of mRNA in colon tissues showed that Shuidouchi extraction can upregulate the expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), c-Kit, and the stem cell factor (SCF). Furthermore, it can downregulate the expression of inducible nitric oxide synthase (iNOS), interleukin-8 (IL-8), and C-X-C chemokine receptor type 2 (CXCR2) in the colon of mice with colitis. Further experimental results showed that Shuidouchi could reduce the protein expression of interleukin 6 (IL-6), IL-12, and tumor necrosis factor-α (TNF-α) in colitic mice. Therefore, the improved processing of Shuidouchi inhibits colitis, which is directly related to the high content of soybean isoflavones.


2015 ◽  
Vol 95 (7) ◽  
pp. 728-748 ◽  
Author(s):  
Hiroki Saijo ◽  
Norifumi Tatsumi ◽  
Seiji Arihiro ◽  
Tomohiro Kato ◽  
Masataka Okabe ◽  
...  

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  

2000 ◽  
Vol 279 (6) ◽  
pp. F1110-F1115 ◽  
Author(s):  
Lieming Xu ◽  
Ethan P. Carter ◽  
Mamiko Ohara ◽  
Pierre-Yves Martin ◽  
Boris Rogachev ◽  
...  

Cirrhosis is typically associated with a hyperdynamic circulation consisting of low blood pressure, low systemic vascular resistance (SVR), and high cardiac output. We have recently reported that nonspecific inhibition of nitric oxide synthase (NOS) with nitro-l-arginine methyl ester reverses the hyperdynamic circulation in rats with advanced liver cirrhosis induced by carbon tetrachloride (CCl4). Although an important role for endothelial NOS (eNOS) is documented in cirrhosis, the role of neuronal NOS (nNOS) has not been investigated. The present study was carried out to specifically investigate the role of nNOS during liver cirrhosis. Specifically, physiological, biochemical, and molecular approaches were employed to evaluate the contribution of nNOS to the cirrhosis-related hyperdynamic circulation in CCl4-induced cirrhotic rats with ascites. Cirrhotic animals had a significant increase in water and sodium retention. In the aorta from cirrhotic animals, both nNOS protein expression and cGMP concentration were significantly elevated compared with control. Treatment of cirrhotic rats for 7 days with the specific nNOS inhibitor 7-nitroindazole (7-NI) normalized the low SVR and mean arterial pressure, elevated cardiac index, and reversed the positive sodium balance. Increased plasma arginine vasopressin concentrations in the cirrhotic animals were also repressed with 7-NI in association with diminished water retention. The circulatory changes were associated with a reduction in aortic nNOS expression and cGMP. However, 7-NI treatment did not restore renal function in cirrhotic rats (creatinine clearance: 0.76 ± 0.03 ml · min−1· 100 g body wt−1in cirrhotic rats vs. 0.79 ± 0.05 ml · min−1· 100 g body wt−1in cirrhotic rats+7-NI; P NS.). Taken together, these results indicate that nNOS-derived NO contributes to the development of the hyperdynamic circulation and fluid retention in cirrhosis.


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