The effects of low dose leukotriene receptor antagonist therapy on airway remodeling and cysteinyl leukotriene expression in a mouse asthma model

Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. The cysteinyl leukotrienes (LTC4, D4 and E4) are known to play important roles in the pathobiology of asthma. To evaluate the effect of low dose montelukast (MK) on the development of airway remodeling using a chronic murine model of allergic airway inflammation with subepithelial fibrosis, BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on days 0 and 14, received intranasal OVA periodically on days 14-75. MK treated mice received montelukast sodium intraperitoneally on days 26-75. The OVA sensitized/challenged mice developed an extensive eosinophil cell inflammatory response, goblet cell hyperplasia, mucus occlusion, and smooth muscle hypertrophy of the airways. In addition, in OVA sensitized/challenged mice, dense collagen deposition/fibrosis was seen throughout the lung interstitium surrounding the airways, blood vessels, and alveolar septae. The cysteinyl leukotriene 1 (CysLT1) receptor antagonist, MK significantly reduced the airway eosinophil infiltration, goblet cell hyperplasia, mucus occlusion, and lung fibrosis except airway smooth muscle hypertrophy in the OVA sensitized/challenged mice. The OVA sensitized/challenged mice had significantly increased epithelial desquamation compared with control mice. MK markedly reduced epithelial desquamation of airways in OVA/MK treated animals compared with OVA sensitized/challenged mice. MK treatment did not affect the levels of CysLT in lung tissue. Our results show that the important role of cysteinyl leukotrienes in the pathogenesis of asthma. Lower dose of CysLT1 receptor antagonism has a significant anti-inflammatory effect on allergen-induced lung inflammation and fibrosis but not airway smooth muscle hypertrophy in an animal model of asthma.

Effects of polysaccharides from cryptoporus volvatus(peck) schear on leukotrienes generation in guinea pig lung / 中国药理学通报

AIM: To study the effects of polysaccharides of ferment cultured cryptoporus volvatus (CVPS) on release of leukotrienes from guinea pig lung and Schultz - Dale reaction. METHODS: The bioassay method and reversed phase high-performance liquid chromatography (RP-HPLC) were used to analyze SRS-A or LTD4 from sensitized or normal guinea pig, after challenged with antigen or A23187 respectively. The antiallergic effects of CVPS were evaluated with Schultz-Dale reaction. RESULTS: The release of SRS-A or LTD4 from sensitized or normal guinea pigs were greatly reduced by CVPS after antigen or A23187 challenge. The CVPS could also inhibit the Schultz-Dale reaction of sensitized guinea pig (IC50 = 0.49 g·L-1). CONCLUSION: The effects of CVPS involved in inhibiting release of leukotrienes from lung and antiallergy.

Release of arachidonic acid metabolites from blood by cultivation of human amniotic fluid with oneself blood / 中国病理生理杂志

AIM: To investigate the effect of human amniotic fluid on the release of thromboxane A 2 (TXA 2), prostaglandin I 2 (PGI 2) and Leukotriene C 4(LTC 4) from blood cells. METHODS: 1 mL human amniotic fluid and 10 mL oneself blood collected from 38-41 weeks with cesarean section were cultured at 37℃ for 30 min, and then centrifuged. The supernatants were taken and stored at -70℃. TXB 2 and 6-Keto-PGF 1? of the superntants were determined by radioimmunoassay and LTC 4 by enzyme immunoassay. RESULTS: It was found that the levels of TXB 2 and LTC 4 in blood were elevated from (63.5?52.0) ng/L and (40.1?39.2) ng/L to (189.1?102.0) ng/L and (293.5?206.1) ng/L respectively (P0.05).CONCLUSION: Amniotic fluid might stimulate the release of TXA 2 and LTC 4 from blood, it might affect the balance of TXA 2 and PGI 2 in blood, which might play an important role in the pathogenesis of amniotic fluid embolism.

Influence of LTC_4 on the microcirculation of the gastric mucosa and its effect on acute gastric mucosal injury / 中国病理生理杂志

The author explored the influence of exogenous LTC_4 (0.1 ng. 100g~(-1),iv) on the microcirculation of gastric mucosa and its effect on acute gestric mucosal injury. Male Wistar rats underwent a fast of 24 hours before the experiment and could drink water freely during this period. The results showed: 1. The caliber of the gastric mucosal superficial capillaries thinned and part of the capillaries disappeared. The caliber of collecting venule thinned also. After 10 minutes there were remarkable venous stasis and heamorrhage. 2. It was confirmed by the method of hydrogen clearence that the gastric mucosal flow reduced significantly. After 15 minutes of the injection, it decreased from original 1.230?0.093 to 0.521?0.079 ((?)+SE) ml, min~(-1). 100g~(-1) (P

The inhibitory effects of diethylcarbamazine citrate on hypoxic pulmonary vasoconstriction in dogs / 中国病理生理杂志

The effects of diethylcarbamazine citrate (DEC), a lipooxygenase inhibitor, on hypoxic pulmonary vasoconstriction (HPV) in dogs were studied, The results showed that HPV was significantly inhibited after the intravenous administration of DEC, and that the inhibitory effect of DEC on HPV had seemingly no association with the decrease of systemic blood pressure and depression of cardiac function induced by DEC. It is suggested that leukotrienes play a role of mediator in HPV in dogs.