alpha-naphthyl-thiourea and Pleural-Effusion

We assessed the effects of dexmedetomidine in a rat model of α-naphthylthiourea (ANTU)-induced acute lung injury.. Forty Wistar Albino male rats weighing 200-240 g were divided into 5 groups (n = 8 each), including a control group. Thus, there were one ANTU group and three dexmedetomidine groups (10-, 50-, and 100-μg/kg treatment groups), plus a control group. The control group provided the normal base values. The rats in the ANTU group were given 10 mg/kg of ANTU intraperitoneally and the three treatment groups received 10, 50, or 100 μg/kg of dexmedetomidine intraperitoneally 30 min before ANTU application. The rat body weight (BW), pleural effusion (PE), and lung weight (LW) of each group were measured 4 h after ANTU administration. The histopathologic changes were evaluated using hematoxylin-eosin staining.. The mean PE, LW, LW/BW, and PE/BW measurements in the ANTU group were significantly greater than in the control groups and all dexmedetomidine treatment groups (P < 0.05). There were also significant decreases in the mean PE, LW, LW/BW and PE/BW values in the dexmedetomidine 50-μg/kg group compared with those in the ANTU group (P < 0.01). The inflammation, hemorrhage, and edema scores in the ANTU group were significantly greater than those in the control or dexmedetomidine 50-μg/kg group (P < 0.01).. Dexmedetomidine treatment has demonstrated a potential benefit by preventing ANTU-induced acute lung injury in an experimental rat model. Dexmedetomidine could have a potential protective effect on acute lung injury in intensive care patients.

Topics: Acute Lung Injury; Adrenergic alpha-2 Receptor Agonists; Animals; Dexmedetomidine; Disease Models, Animal; Drug Interactions; Lung; Male; Pleural Effusion; Pneumonia; Pulmonary Edema; Rats; Rats, Wistar; Rodenticides; Thiourea

This study was designed to investigate the possible participation of urethane, pentobarbital sodium and thiopental sodium anaesthesia in the lung oedema induced by alpha-naphthylthiourea (ANTU), which is a well known noxious chemical agent in the lung. ANTU when injected intraperitoneally (i.p.) into rats (10 mg x kg (-1) i.p.) produced lung oedema as indicated by an increase in lung weight/body weight (LW/BW) ratio and pleural effusion (PE) reaching a maximum within 4 h. Administration of urethane prior to ANTU, at doses of 100 and 200mg(100g)(-1), elicited a significant and dose-dependent inhibition in LW/BW ratio and PE. Thiopental sodium at doses of 25, 50 mg x kg (-1), also produced a significant and dose-dependent inhibition of both parameters. Prior i.p. injection of pentobarbital sodium at a dose of 40 mg x kg (-1) elicited a significant inhibition in both parameters. These results suggest that i.p. urethane, thiopental sodium and pentobarbital sodium pretreatment have a prophylactic effect on ANTU-induced lung injury in rats. The possible role of the anaesthetics in lung oedema induced by ANTU and the possible underlying mechanisms are discussed.

Topics: Animals; Hypnotics and Sedatives; Male; Organ Size; Pentobarbital; Pleural Effusion; Pulmonary Edema; Rats; Thiopental; Thiourea; Urethane

Pleural fluid (PF) proteins either derive from serum by diffusion or are locally secreted within the pleural space. Another hypothetical origin is a leakage of lung secretory proteins across the visceral pleura. To test this hypothesis, we investigated the occurrence, sources, and determinants in PF of CC16, a small-size and readily diffusible protein of 16 kDa secreted by bronchiolar Clara cells. CC16 concentration was determined by a sensitive latex immunoassay in serum and PF of 117 subjects (86 exudates and 31 transudates) and, for purpose of comparison, in ascites samples from another group of 38 subjects (7 exudates and 31 transudates). CC16 was also studied in serum and PF of normal rats and in rats with pleural exudate induced by alpha-naphthyl-thiourea (ANTU). The levels of CC16 in PF and ascites were highly correlated with that in serum, suggesting a diffusional exchange across the pleural/blood and peritoneal/blood barriers. Whereas CC16 occurs at similar levels in ascites and serum, the protein was found to be more concentrated in PF than in serum in both humans (geometric mean in microg/L, 26.2 versus 14.6, p < 0.0001) and rats (213 versus 16.2, p < 0.001). A local synthesis of CC16 appeared unlikely in view of the lack of CC16-immunostaining in pleura of both species. The only plausible explanation for these findings is that CC16 in PF originates from two sources: diffusion from plasma and a leakage from the lung into the pleural space across the semipermeable visceral pleura. This interpretation is supported by a markedly increased leakage of CC16 in experimental exudates induced by ANTU and the finding of high CC16 concentrations in human transudates associated with congestive heart failure, two conditions wherein PF has been shown to arise from the interstitial spaces of the lung.

Topics: Aged; Animals; Ascites; Biomarkers; Blood Proteins; Bronchi; Creatinine; Diffusion; Disease Models, Animal; Enzyme Inhibitors; Exudates and Transudates; Female; Heart Failure; Humans; Lung; Male; Middle Aged; Peritoneum; Phospholipases A; Pleura; Pleural Effusion; Proteins; Rats; Rats, Sprague-Dawley; Smoking; Thiourea; Uteroglobin

This study was designed to investigate the possible participation of the L-arginine-nitric oxide (NO) pathway in the lung oedema induced by alpha-naphthylthiourea, which is a well-known noxious chemical agent in the lung. Lung oedema was assessed by measuring fluid accumulation in the pleural cavity and the lung weight/body weight ratio following alpha-naphthylthiourea injection. Administration of NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, prior to alpha-naphthylthiourea, produced a significant inhibition of pleural effusion and lung weight/body weight ratio in a dose-dependent manner. L-Arginine, but not D-arginine, when used higher doses (above 300 mg/kg) prior to alpha-naphthylthiourea injection caused a significant inhibition of pleural effusion without altering lung weight/body weight ratio. Lower doses of L-arginine (below 100 mg/kg) did not elicit an inhibitory effect against alpha-naphthylthiourea-induced pulmonary damage. However, lower doses of L-arginine greatly potentiated the inhibitory effect of NG-nitro-L-arginine-methyl ester against alpha-naphthylthiourea-induced lung oedema when used in combination. The interesting aspect of this study is the inhibition by NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, and L-arginine, an endogenous donor of NO, of the lung oedema induced by alpha-naphthylthiourea. The possible role of the L-arginine-NO pathway in lung oedema induced by alpha-naphthylthiourea and the possible underlying mechanisms are discussed.

Topics: Animals; Arginine; Drug Synergism; Enzyme Inhibitors; Female; Lung; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pleural Effusion; Pulmonary Circulation; Pulmonary Edema; Rats; Stereoisomerism; Thiourea

Alpha-naphthylthiourea when injected intraperitoneally to rats (10 mg kg-1 i.p.) produced lung oedema as indicated by an increase in lung weight/body ratio and pleural effusion reaching a maximum within 4 hours. Prior intravenous single bolus injection of endothelin-1 elicited a significant and dose-dependent inhibition in both parameters. However, prior i.v. injection of angiotensin II using relatively higher doses did not alter the oedema-producing effect of alpha-naphthylthiourea indicating a characteristic for endothelin-1. The inhibitory effect of endothelin-1 on pleural effusion is more prominent than lung weight/body weight ratio. The resolution of lung oedema by single bolus i.v. injection of endothelin-1 is probably due to the acute long-lasting and potent vasoconstrictor effect of the peptide and its large accumulation in lung tissue. Phosphoramidon, an inhibitor of endothelin converting enzyme, did not alter the oedema producing effect of alpha-naphthylthiourea indicating the lack of the participation of endothelin-peptide cascade to this pathological event. Bosentan, a non-selective receptor blocker of endothelin-1, did not inhibit the preventive effect of the peptide against alpha-naphthylthiourea-induced lung oedema. Possible mechanisms of the acute effect of endothelin-1 on lung oedema are discussed.

Topics: Angiotensin II; Animals; Aspartic Acid Endopeptidases; Body Weight; Bosentan; Endothelin-1; Endothelin-Converting Enzymes; Glycopeptides; Male; Metalloendopeptidases; Organ Size; Pleural Effusion; Protease Inhibitors; Pulmonary Edema; Rats; Sulfonamides; Thiourea

alpha-Naphthylthiourea (ANTU) causes pulmonary edema and pleural effusion in rats. It has been suggested that ANTU pneumotoxicity may be mediated by blood neutrophils (PMNs) via the release of reactive oxygen species. Accordingly, we tested the effect of technical grade ANTU (tANTU) on the ability of rat peritoneal PMNs to release superoxide (O2-). tANTU did not itself stimulate O2- production by PMNs, but it increased the O2- released in response to PMN stimulation by phorbol myristate acetate (PMA). This effect was dependent upon the amount of tANTU added. In PMNs activated in vitro by a submaximal PMA stimulus, addition of 20 micrograms/ml tANTU doubled superoxide release. When tANTU was recrystallized from ethanol, the purified ANTU was not effective in potentiating the effect of PMA on PMNs. This suggests that an impurity in technical grade ANTU is capable of increasing O2- release by stimulated PMNs. tANTU and recrystallized ANTU caused similar pneumotoxicity in rats in vivo, suggesting that the unidentified impurity does not markedly influence the biologic effects of ANTU.

Topics: Animals; Drug Contamination; Drug Synergism; In Vitro Techniques; Male; Neutrophils; Pleural Effusion; Pulmonary Edema; Rats; Superoxides; Tetradecanoylphorbol Acetate; Thiourea

alpha-Naphthyl thiourea ( ANTU ) produces pulmonary endothelial injury, pulmonary edema, and pleural effusions in rats in a dose-dependent manner. Since prostaglandins of the E series have been shown to modulate inflammatory responses in vivo and neutrophil and platelet function in vitro we investigated the effects of prostaglandin E1 (PGE1) on ANTU -induced lung injury. Systemic administration of 15-(S)-15-methyl-PGE1 (15-M-PGE1), a stable analog of PGE1, potentiated lung injury induced by ANTU in a dose- and time-dependent manner. 15-M-PGE1 (1 mg/kg, subcutaneously) administered 1 hour prior to ANTU treatment (1 mg/kg, intraperitoneally) resulted in a 164% increase (p less than 0.001) in pleural effusion formation and a 42% increase (p less than 0.02) in wet lung weight at 4 hours after ANTU administration. This was associated with increased pulmonary endothelial cell blebbing and gap formation with a decrease in the number of platelet thrombi in 15-M-PGE1-treated animals compared with controls. 15-(S)-15-methyl-prostaglandin F2 alpha, was less effective than 15-M-PGE1 in potentiating ANTU -induced lung injury. Platelet depletion, but not neutrophil depletion, also potentiated ANTU -induced lung injury, suggesting a protective role for platelets. Platelets isolated from 15-M-PGE1-treated animals demonstrated an approximately 50% decreased aggregation response to adenosine diphosphate. 15-M-PGE1 (1 mg/kg) treatment combined with platelet depletion resulted in a 1.7-fold increase (p less than 0.01) in pleural effusions in ANTU -treated (1 mg/kg) animals compared with platelet depletion alone. These studies indicate that systemic treatment of rats with 15-M-PGE1 will potentiate ANTU -induced lung injury. This injury may be in part secondary to the ability of 15-M-PGE1 to inhibit platelet function. However, platelet depletion studies suggest that 15-M-PGE1 has additional effects, possibly on endothelial cells and/or vascular smooth muscle cells that contribute to the potentiation of ANTU -induced lung injury.

Topics: Alprostadil; Animals; Blood Platelets; Dose-Response Relationship, Drug; Lung; Male; Microscopy, Electron; Pleural Effusion; Prostaglandins E, Synthetic; Pulmonary Edema; Rats; Rats, Inbred Strains; Rodenticides; Specific Pathogen-Free Organisms; Thiourea; Time Factors

Topics: Animals; Exudates and Transudates; Lung Diseases; Pleura; Pleural Effusion; Pulmonary Edema; Rats; Thiourea

Topics: Animals; Dogs; Edema; Lung; Pleural Effusion; Pleurisy; Pulmonary Edema; Rats; Thiourea

Topics: Animals; Blood; Cholesterol; Dogs; Plasma; Pleural Effusion; Pleurisy; Thiourea