Adverse effects of (15S)-15-methyl-prostaglandin E1 in normal and paraquat-exposed rats

Williams, J. H.; Fairshter, Ronald D.; Ulich, Thomas R.; Crosby, Sheena; Chen, M.; Rosario, Lauren; Vaziri, Nosratola D.

doi:10.1016/0041-008x(88)90393-6

Cited by 4 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dinis-Oliveira and colleagues (47) found that dexemethosone improved survival of PQ-poisoned rats due to its anti-inflammatory activity, and another specific anti-inflammatory agent, Montelukast, increased the 7-day survival of PQ-poisoned rats from 30 to 80% by blocking the action of leukotriene D4 in the lungs and bronchial tubes (48). However, anti-inflammatory agent, prostaglandin E1 analog, accelerated death in PQ poisoning (49). Importantly, however, it was recently reported that immunosuppressive therapy saved approximately 25% of human patients from PQ poisoning (43).…”

Section: Discussionmentioning

confidence: 99%

Complement Inhibition Alleviates Paraquat-Induced Acute Lung Injury

Sun

Wang

Zhao

et al. 2011

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

The widely used herbicide, paraquat (PQ), is highly toxic and claims thousands of lives from both accidental and voluntary ingestion. The pathological mechanisms of PQ poisoning-induced acute lung injury (ALI) are not well understood, and the role of complement in PQ-induced ALI has not been elucidated. We developed and characterized a mouse model of PQ-induced ALI and studied the role of complement in the pathogenesis of PQ poisoning. Intraperitoneal administration of PQ caused dose- and time-dependent lung damage and mortality, with associated inflammatory response. Within 24 hours of PQ-induced ALI, there was significantly increased expression of the complement proteins, C1q and C3, in the lung. Expression of the anaphylatoxin receptors, C3aR and C5aR, was also increased. Compared with wild-type mice, C3-deficient mice survived significantly longer and displayed significantly reduced lung inflammation and pathology after PQ treatment. Similar reductions in PQ-induced inflammation, pathology, and mortality were recorded in mice treated with the C3 inhibitors, CR2-Crry, and alternative pathway specific CR2-fH. A similar therapeutic effect was also observed by treatment with either C3a receptor antagonist or a blocking C5a receptor monoclonal antibody. Together, these studies indicate that PQ-induced ALI is mediated through receptor signaling by the C3a and C5a complement activation products that are generated via the alternative complement pathway, and that complement inhibition may be an effective clinical intervention for postexposure treatment of PQ-induced ALI.

show abstract

Section: Discussionmentioning

confidence: 99%

Complement Inhibition Alleviates Paraquat-Induced Acute Lung Injury

Sun

Wang

Zhao

et al. 2011

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…With the development of a sensitive and specific technique, bronchoalveolar lavage (BAL), in which the cellular and noncellular constituents of the epithelial surface of the lower respiratory tract can be easily sampled, it has been possible to detect and quantify early biochemical indices of CP-induced pulmonary toxicity. This approach has also been used to monitor pulmonary injury in several other species: dogs [13,20], monkeys [43], rats [48], hamsters [17,18], rabbits [46], and mice [30]. In the context of these considerations, knowledge of the broncholaveolar lavage fluid (BALF) biomarkers in the evaluation of early lung injury becomes important.…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function

Venkatesan

Chandrakasan

1994

Lung

View full text Add to dashboard Cite

The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury.

show abstract