Pulmonary toxicity of thuringiensin administered intratracheally in Sprague-Dawley rats.
The purpose of this work is to evaluate the pulmonary toxicity of purified thuringiensin in Sprague-Dawley rats. Rats were intratracheally instillated with 0, 0.4, 0.8, 1.6, 3.2, 6.4 and 9.6 mg/kg body weight of thuringiensin. The results indicated that the acute pulmonary LD(50) of thuringiensin for rats was 4.4 mg/kg. The total number of inflammatory cells and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage (BAL) fluid increased in a dose-dependent manner after thuringiensin instillation. Furthermore, an effective dose of 1.6 mg/kg was selected for the time course study of pulmonary toxicity. The treated animals showed a significant increase in the weights of the lungs, hydroxyproline levels in the lungs and total number of cells in BAL fluid 2, 4, 7, 14, 28 and 56 days after treatment. In comparison with the control, the total protein concentrations in BAL fluid were increased by 361, 615, 116, 41, 34 and 41%, after 2, 4, 7, 14, 28 and 56 days, respectively. The LDH activity in BAL fluid showed a significant increase after 1, 2, 4, 7, 14, 28 and 56 days. The increases in fibronectin levels were 164, 552, 490, 769, 335, 257 and 61% at the corresponding times, but neither tumor necrosis factor nor interleukin-1 increased. The treated rats presented abnormal histology including distributed inflammation in the bronchioles and alveoli, bronchial cellular necrosis on days 1 and 2, and areas of septal thickening with cellular infiltration and collagen deposit in the intestinal and alveolar spaces on days 4-56. Based on these biochemical and pathological parameters, intratracheal instillation of purified thuringiensin might cause significant pulmonary toxicity in rats.
Tsai
San-Fu
SF
Department of Veterinary Medicine, National Chung-Hsing University, 250 Kuang Road, Taichung 402, Taiwan, ROC.
Liu
Bing-Lan
BL
Liao
Jiunn-Wang
JW
Wang
Jiunn-Shiow
JS
Hwang
Jenn-Sheng
JS
Wang
Shun-Cheng
SC
Tzeng
Yew-Min
YM
Ho
Shu-Peng
SP
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D011506:Proteins / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013400:Sugar Acids / Q000008:administration & dosage / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005353:Fibronectins; D007375:Interleukin-1; D011506:Proteins; D013400:Sugar Acids; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; C068295:thuringiensin; D000241:Adenosine; D006909:Hydroxyproline