Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms.

Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.

Toxicity study of mineral medicine haematitum.

ETHNOPHARMACOLOGICAL RELEVANCE: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms. AIM OF THE STUDY: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug. MATERIALS AND METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels. RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum. CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.

[Pharmacokinetic study on baicalin of Qingkailing injection in rats].

OBJECTIVE: Studying the metabolic pharmacokinetic of baicalin of Qingkailing injection in rat, to search for effector substance of Qingkailing injection in vivo. METHOD: Qingkailing sterile injection powder was given by caudal vein, then blood, liver and lung were collected in various time, the concentration of baicalin from samples were determined by HPLC-MS. Pharmacokinetic evaluation was carried out using the 3P87. RESULT: After Qingkailing injection, Baicalin was consistent with two-compartment model in rat. 45 min, the concentration of baicalin in hepatic tissue reached maximum, followeded by decrease sharply, 120 min began to rise slowly, present double hump phenomenon. In lung, baicalin concentration was far more than in liver, was eliminated more slowly, but they have the same t(max). CONCLUSION: After Qingkailing injection, baicalin distributed quickly to liver and lung, baicalin is one of effector substance of qingkailing injection in vivo. Baicalin might have hepatoenteral circulation.

[Studies on mechanism of antiasthmatic and anti-inflammatory actions of CDCA].

OBJECTIVE: To observe antiasthmatic and anti-inflammatory actions mechanisms of CDCA. METHOD: The content of NO was determined by method of nitroreductase chromatometry in serum and trachea tissue. The content of cAMP was analysed by method of competitive protein-binding assay. The content of PGE2 was determined by method of ultraviolet spectrophotometry. RESULT: CDCA significantly decreased the content of NO of serum and trachea tissue in mice. CDCA increased greatly the content of cAMP of trachea tissue in rats. CDCA significantly decreased the content of PGE2 of trachea and lung tissue in mice. CONCLUSION: Mechanisms of antiasthmatic and anti-inflammatory actions of CDCA are related to increasing the content of cAMP in trachea tissue and decreasing the constituent of NO and PGE2 in body.

[Influence of compound biejia ruangan prescription on extracelluar matrix in bleomycin induced pulmonary fibrosis rats].

OBJECTIVE: To study the influence of compound Biejia Ruangan Prescription (CBRP) on extracelluar matrix in bleomycin induced pulmonary fibrosis rats. METHOD: 54 male Sprague-Dawley rats were randomly divided into 6 groups (9 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low CBRP groups were injected with bleomycin A5 by trachea, and rats in sham-model control group with same volume normal saline. 29 days after the injection, CBRP solution of different dosages (1.4 g x kg(-1), 0.7 g x kg(-1), 0.35 g x kg(-1)) was respectively given to rats in the high, moderate and low CBRP group by gavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1)) was given to those in positive medicine control group. On the 80th day, the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum were determined, the determination of hydroxyproline in lung homogenates was analyzed, and the right lung was incised to make pathological sections which were stained with Hematoxylin-Eosin (HE) and Masson staining for pathological diagnosis. RESULT: CBRP could decrease the levels of III-collagen, IV-collagen, laminin and hyaluronic acid in the serum. CONCLUSION: CBRP may play its therapeutic role by leveling down the content of extracellular matrix in rats with pulmonary fibrosis induced by Bleomycin A5.

Functional residual capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation.

Functional residual capacity (FRC), rib cage and abdominal dimensions (rc-ab), central blood volume (CBV), and extra vascular lung water (EVLW) were measured in six lung-healthy subjects awake and during halothane anesthesia, muscle paralysis, and mechanical ventilation. FRC was assessed by multiple breath nitrogen washout, rc-ab dimensions by computerized tomography, and CBV and EVLW by a double-indicator dilution technique (thermo-dye). During anesthesia, FRC decreased by 0.5 1 (17%). The cross-sectional chest area was reduced by 12-20 cm2, causing an approximate reduction in thoracic volume by 0.3 1. Concomitantly, the diaphragm was moved cranially by an average of 1.9 cm, diminishing the thoracic volume a further 0.5 1. The abdominal cross-sectional area did not alter significantly, despite the shift of the diaphragm. CBV decreased by 0.3 1. EVLW did not change significantly. It is concluded that the thoracic volume is reduced during halothane anesthesia, muscle paralysis, and mechanical ventilation as a result of cranial shift of the diaphragm and reduction in transverse area. The decrease in thoracic volume is accompanied by a reduction in FRC and a displacement of blood from the thorax to the abdomen, the transverse area of the latter thus being maintained despite the shift of the diaphragm.

The interaction of neuromuscular relaxants with rabbit lung muscarinic receptors.

The interaction of muscle relaxants with airway muscarinic receptors of rabbit lung was investigated in vitro by the [3H]QNB binding technique. Pancuronium, vecuronium, alcuronium and succinyl choline chloride (SCC) inhibited the binding of [3H]QNB to rabbit lung muscarinic receptors in a dose-dependent manner. The values of IC50 (the concentration giving 50% inhibition) of pancuronium, vecuronium, alcuronium and SCC were 1.54 x 10(-5), 2.52 x 10(-5), 8.40 x 10(-5), and 4.00 x 10(-3) mol/l respectively. As the values of Kd increased with minimal change in the value of Bmax, while not influencing the number of receptors, these muscle relaxants had an inhibitory action on the affinity of muscarinic receptors to [3H]QNB in the order: pancuronium greater than or equal to vecuronium greater than alcuronium greater than SCC. Applying IC50 values to human conditions, clinical doses of these muscarinic relaxants are unlikely to exhibit any significant vagolytic action in lung tissue.

Paralysis of the preterm rabbit fetus inhibits the pulmonary uptake of intraamniotic iron dextran.

OBJECTIVE: Whether fetal breathing movements or gasping result in the movement of amniotic fluid substances into the distal airways remains controversial. We evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary distribution of iron dextran. STUDY DESIGN: Laparotomy was performed on 10 New Zealand White rabbits of 25 days' gestation (term 31 days) under general anesthesia. Fetuses in one uterine horn were given an intramuscular injection of pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml) was injected into the amniotic sac of all fetuses. The laparotomy was closed, and 20 to 24 hours later the fetuses were removed by hysterotomy and assessed for paralysis. Necropsy was performed. Lungs were stained with prussian blue and evaluated histologically for the presence of iron. RESULTS: A total of 92 pups were delivered (49 given pancuronium, 43 given normal saline solution), of which 64 were born alive. There were no differences between groups for live births (31 pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups given normal saline solution demonstrated more breathing motions, spontaneous movement, and brown (color of iron dextran) stomach contents than did the pups given pancuronium (p < 0.001). At necropsy a greater number of control pups (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p < 0.001). Lung histologic examination showed that more control pups (29/29) had iron in the trachea and main bronchi compared with pancuronium pups (0/27, p < 0.001), and more control pups (29/29) had iron in the distal lung airways compared with pancuronium pups (0/27, p < 0.001). With use of the Optimas Image Analysis System, iron in the lungs of control pups was found to be equally distributed between right versus left lungs, upper half versus lower half lungs, and anterior versus posterior lung sections. More iron was identified in the central airways than in the periphery (p < 0.001). CONCLUSION: We conclude that paralysis prevents the uptake of iron dextran into the main and distal airways of the rabbit fetus. Although lung fluid production results in a net efflux of fluid, we speculate that fetal breathing movements can result in the movement of fluid into distal airways and potentially provide fetal therapy.