Role of oxidative stress in thuringiensin-induced pulmonary toxicity.
To understand the effect of thuringiensin on the lungs tissues, male Sprague-Dawley rats were administrated with thuringiensin by intratracheal instillation at doses 0.8, 1.6 and 3.2 mg/kg of body weight, respectively. The rats were sacrificed 4 h after treatment, and lungs were isolated and examined. Subsequently, an effective dose of 1.6 mg/kg was selected for the time course study (4, 8, 12, and 24 h). Intratracheal instillation of thuringiensin resulted in lung damage, as evidenced by increase in lung weight and decrease in alkaline phosphatase (10-54%), an enzyme localized primarily in pulmonary alveolar type II epithelial cells. Furthermore, the administration of thuringiensin caused increases in lipid peroxidation (21-105%), the indices of lung injury. In addition, the superoxide dismutase (SOD) and glutathione (GSH) activities of lung tissue extracts were measured to evaluate the effect of thuringiensin on antioxidant defense system. The SOD activity and GSH content in lung showed significant decreases in a dose-related manner with 11-21% and 15-37%, respectively. Those were further supported by the release of proinflammatory cytokines, as indicated by increases in IL-1beta (229-1017%) and TNF-alpha (234%) levels. Therefore, the results demonstrated that changes in the pulmonary oxidative-antioxidative status might play an important role in the thuringiensin-induced lung injury.
Tsai
San-Fu
SF
Division of Applied Toxicology, Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Executive Yuan, Taichung, Taiwan, ROC. sftsai@tactri.gov.tw
Yang
Chi
C
Liu
Bing-Lan
BL
Hwang
Jenn-Sheng
JS
Ho
Shu-Peng
SP
D000241:Adenosine / Q000031:analogs & derivatives* / Q000633:toxicity; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013400:Sugar Acids / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
D001427:Bacterial Toxins; D016207:Cytokines; D013400:Sugar Acids; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D005978:Glutathione; C068295:thuringiensin; D000241:Adenosine