Effect of leukocyte inhibitors benzydamine and cyclophosphamide, on lung injury caused by Tityus discrepans scorpion venom.
We studied the effects of benzydamine (BZ) and cyclophosphamide (CP) on acute lung injury caused by Tityus discrepans venom. Mice (male, IVIC strain, approximately 25g) were pretreated with either BZ (20microg/g) or CP (100microg/g) i.p. or saline. Envenoming (2microg/g mouse) was induced sc. Lung fraction area occupied by fibrin (FF), nuclei (NF), alveolar space (AS) and parenchyma (PF) were determined. Venom increased FF, NF and PF, significantly, and decreased AS. BZ antagonised venom's effect on FF sharply, antagonised partially effects on PF and AS, but was not able to antagonise effect on NF. CP abolished venom effects on NF, AS and PF, but was not able to antagonise the effect on FF. CP was slightly less effective than BZ in reducing FF. Fibrin deposition was associated to leukocyte sequestration. Blocking pro-inflammatory leukocyte metabolic pathways with BZ diminished FF, suggesting that neutrophil activation, inflammation and coagulation are correlated in the genesis of scorpionism acute lung injury.
D'Suze
Gina
G
Laboratory on Cellular Neuropharmacology, IVIC CBB, Apdo 20632, Caracas 1020-A, Venezuela. gdsuze@ivic.ve
Díaz
Patricia
P
Salazar
Victor
V
Sevcik
Carlos
C
Brazón
Josmary
J
D000818:Animals; D001591:Benzydamine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology; D012604:Scorpion Venoms / Q000633:toxicity*
D012604:Scorpion Venoms; D001591:Benzydamine; D003520:Cyclophosphamide