scholarly journals 17β-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4729-4737 ◽  
Author(s):  
Sayyed A. Hamidi ◽  
Kathleen G. Dickman ◽  
Hasan Berisha ◽  
Sami I. Said
Keyword(s):  
Lung Injury ◽  
Oxidant Stress ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Experimental Models ◽  
Acute Injury ◽  
Normal Lung ◽  
Lung Weight ◽  
Lung Protection ◽  
17Β Estradiol

Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60–90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen.

Therapeutic Effects of Baicalin on Lipopolysaccharide-Induced Acute Lung Injury in Rats

2008 ◽  
Vol 36 (02) ◽  
pp. 301-311 ◽  
Author(s):  
Kun-Lun Huang ◽  
Chien-Sheng Chen ◽  
Ching-Wang Hsu ◽  
Min-Hui Li ◽  
Hung Chang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Histological Finding ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Blue Dye ◽  
Therapeutic Effects ◽  
Lung Weight ◽  
Lactate Dehydrogenase Activity

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury.

Paraquat-induced lung injury: prevention by vasoactive intestinal peptide and related peptide helodermin

1993 ◽  
Vol 265 (4) ◽  
pp. L369-L373 ◽  
Author(s):  
H. Pakbaz ◽  
H. D. Foda ◽  
H. I. Berisha ◽  
M. Trotz ◽  
S. I. Said
Keyword(s):  
Antioxidant Activity ◽  
Lung Injury ◽  
Guinea Pig ◽  
Vasoactive Intestinal Peptide ◽  
Airway Pressure ◽  
Perfusion Pressure ◽  
Weight Ratio ◽  
Acute Injury ◽  
Lung Weight ◽  
Mechanically Ventilated

We earlier showed that the neuropeptide vasoactive intestinal peptide (VIP) reduces or prevents acute injury produced in rat lungs by xanthine and xanthine oxidase. We have now examined whether VIP can protect against lung injury induced by paraquat, a prooxidant pesticide. Isolated guinea pig lungs were perfused for 60 min with Krebs-4% albumin and mechanically ventilated with 95% O2-5% CO2. Infusion of paraquat (100 mg/kg) into the pulmonary artery (n = 9 observations) increased peak airway pressure from 10.1 +/- 0.6 to 54.7 +/- 6.5 cmH2O, perfusion pressure from 8.0 +/- 0.5 to 14.9 +/- 3.0 cmH2O, wet-to-dry lung weight ratio to 7.17 +/- 0.37, and bronchoalveolar lavage protein content to 2.70 +/- 0.83 mg/ml (P < 0.01). Pretreatment with 1–3 micrograms.kg-1 x min-1 VIP markedly attenuated or prevented all abnormalities. Of the related peptides tested, helodermin was as effective as VIP, but secretin and glucagon were ineffective. The results demonstrate that VIP and helodermin protect perfused guinea pig lungs against paraquat-induced injury and support the view that VIP has antioxidant activity.

Hypoxia enhances unilateral lung injury by increasing blood flow to the injured lung

1987 ◽  
Vol 63 (6) ◽  
pp. 2516-2523 ◽  
Author(s):  
K. Takeda ◽  
M. J. Knapp ◽  
W. G. Wolfe ◽  
J. D. Crapo
Keyword(s):  
Blood Flow ◽  
Lung Injury ◽  
Left Lung ◽  
Weight Ratio ◽  
Normal Lung ◽  
Lung Edema ◽  
Lung Weight ◽  
Edema Formation ◽  
Concomitant Decrease ◽  
Injured Lung

We hypothesized that in unilateral lung injury, bilateral hypoxic ventilation would induce vasoconstriction in the normal lung, redirect blood flow to the injured lung, and cause enhanced edema formation. Unilateral left lung injury was induced by intrabronchial instillation of 1.5 ml/kg of 0.1 N HCl. After HCl injury, blood flow to the injured left lung decreased progressively from 0.70 +/- 0.04 to 0.37 +/- 0.05 l/min and percent of flow to the injured left lung (QL/QT) decreased from 37.7 +/- 2.2 to 23.6 +/- 2.2% at 240 min. Exposure to hypoxia (12% O2) for three 10-min episodes did not affect QL/QT in normal animals, but after unilateral HCl injury, it caused blood flow to the injured left lung to increase significantly. A concomitant decrease in blood flow occurred to the noninjured right lung, resulting in a significant increase in QL/QT. The enhanced blood flow to the injured lung was associated with a significant increase in the wet-to-dry lung weight ratio in the dependent regions of the injured lung. These findings demonstrate that in unilateral HCl-induced lung injury, transient hypoxia can enhance blood flow to the areas of injury and increase lung edema formation.

Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury

1997 ◽  
Vol 273 (3) ◽  
pp. L504-L512 ◽  
Author(s):  
Y. C. Huang ◽  
P. W. Fisher ◽  
E. Nozik-Grayck ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Average Rate ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
No Production ◽  
Protective Effects ◽  
Lung Weight ◽  
Edema Formation ◽  
No Donors

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

Leukotriene B4 induces lung injury in the rabbit: role of neutrophils and effect of indomethacin

1993 ◽  
Vol 74 (5) ◽  
pp. 2174-2179 ◽  
Author(s):  
K. Yoshimura ◽  
S. Nakagawa ◽  
S. Koyama ◽  
T. Kobayashi ◽  
T. Homma
Keyword(s):  
Arachidonic Acid ◽  
Lung Injury ◽  
Weight Ratio ◽  
Leukotriene B4 ◽  
Arachidonic Acid Metabolism ◽  
Microvascular Permeability ◽  
Lung Edema ◽  
Lung Weight ◽  
Fluid Filtration ◽  
Pmn Leukocytes

The effects of exogenous leukotriene B4 (LTB4) on the pulmonary microvascular permeability and the roles of polymorphonuclear (PMN) leukocytes and the cyclooxygenase products of arachidonic acid in the microvascular response to LTB4 in the isolated non-blood-perfused rabbit lungs were studied. Microvascular permeability and lung edema were evaluated by use of the fluid filtration coefficient (Kf) and the wet-to-dry lung weight ratio (W/D ratio), respectively. Pulmonary capillary pressure was estimated by the double occlusion technique. We studied five groups of lungs: lungs were given 1) both PMN leukocytes and a bolus injection of LTB4 (5 micrograms, n = 6), 2) LTB4 alone (n = 5), 3) PMN leukocytes alone (n = 5), 4) control vehicles (n = 5), or 5) indomethacin (40 micrograms/ml) before PMN leukocytes and LTB4 (n = 6). We observed that LTB4 increased Kf and W/D ratio in the presence of PMN leukocytes in the perfusate without affecting the pulmonary arterial and capillary pressures. Neither LTB4 alone nor PMN leukocytes alone produced changes in Kf and W/D ratio. Indomethacin failed to inhibit the LTB4-induced increases in Kf and W/D ratio. These results suggest that LTB4 produces lung injury that is dependent on PMN leukocytes but not on the cyclooxygenase pathway of arachidonic acid metabolism.

scholarly journals Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Junyan Han ◽  
Deshun Ma ◽  
Miao Zhang ◽  
Xuelian Yang ◽  
Dehong Tan
Keyword(s):  
Body Weight ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Sod Activity ◽  
Protein Levels ◽  
Injury Characteristic ◽  
Dose Dependent

The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-αlevels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent

1992 ◽  
Vol 262 (2) ◽  
pp. L147-L152
Author(s):  
T. Sata ◽  
E. Kubota ◽  
H. P. Misra ◽  
M. Mojarad ◽  
H. Pakbaz ◽  
...  
Keyword(s):  
Free Radical ◽  
Lung Injury ◽  
Guinea Pig ◽  
Weight Ratio ◽  
Spin Trapping ◽  
Lung Weight ◽  
Paramagnetic Resonance ◽  
Arterial Perfusion ◽  
Tert Butyl ◽  
Trapping Agent

The herbicide paraquat causes lung injury that is believed to be oxygen-radical mediated. To further characterize this injury and explore new methods of preventing it, we used the spin-trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) to identify the paraquat radical in lung tissue and to reduce the injury resulting from the subsequent generation of reactive oxygen species. The formation of a paraquat free radical by guinea pig lung was detected under anaerobic conditions by electron paramagnetic resonance spectrometry. Infused (25, 50, or 100 mg/kg) into guinea pig lungs (perfused at constant flow with Krebs solution containing 4% bovine serum albumin and ventilated with 95% O2-5% CO2), paraquat produced dose-dependent increases in peak airway pressure (Paw), mean pulmonary arterial perfusion pressure (Ppa), and wet-to-dry (W/D) lung weight ratio. At 100 mg/kg, paraquat increased Paw by 589.6 +/- 59.8% (mean +/- SE, n = 8) and W/D ratio from 5.33 +/- 0.07 to 6.29 +/- 0.11 (P less than 0.001). Pulmonary vascular leak index increased from 0.40 +/- 0.09 to 1.96 +/- 0.45 (P less than 0.02), without changes in pulmonary microvascular pressure. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha increased, but indomethacin did not reduce the injury. PBN (2.3 mM) markedly attenuated all evidence of lung injury, which was also reduced by catalase, mannitol, ethanol, and vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

Neutrophils in reexpansion pulmonary edema

1988 ◽  
Vol 65 (1) ◽  
pp. 228-234 ◽  
Author(s):  
R. M. Jackson ◽  
C. F. Veal ◽  
C. B. Alexander ◽  
A. L. Brannen ◽  
J. D. Fulmer
Keyword(s):  
Pulmonary Edema ◽  
Weight Ratio ◽  
Intrathoracic Pressure ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Leukotriene B4 ◽  
Albumin Concentration ◽  
Lung Weight ◽  
Reexpansion Pulmonary Edema ◽  
Neutrophil Depletion

This study investigated the possible contribution of neutrophils to development of reexpansion pulmonary edema (RPE) in rabbits. Rabbits' right lungs were collapsed for 7 days and then reexpanded with negative intrathoracic pressure for 2 h before study, a model that creates unilateral edema in the reexpanded lungs but not in contralateral left lungs. Two hours after lung reexpansion, significant increases in lavage albumin concentration (17-fold), percent neutrophils (14-fold), and total number of neutrophils (7-fold) recovered occurred in the reexpanded lung but not in the left. After 2 h of reexpansion increased leukotriene B4 was detected in lavage supernatant from right lungs (335 +/- 33 pg/ml) compared with the left (110 +/- 12 pg/mg, P less than 0.01), and right lung lavage acid phosphatase activity similarly increased (6.67 +/- 0.35 U/l) compared with left (4.73 +/- 0.60 U/l, P less than 0.05). Neutropenia induced by nitrogen mustard (17 +/- 14 greater than neutrophils/microliters) did not prevent RPE, because reexpanded lungs from six neutropenic rabbits were edematous (wet-to-dry lung weight ratio 6.34 +/- 0.43) compared with their contralateral lungs (4.97 +/- 0.04, P less than 0.01). An elevated albumin concentration in reexpanded lung lavage from neutropenic rabbits (8-fold) confirmed an increase in permeability. Neutrophil depletion before reexpansion did not prevent unilateral edema, although neutrophils were absent from lung sections and alveolar lavage fluid from neutropenic rabbits.

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