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Carbon tetrachloride inhibits synthesis of pulmonary surfactant disaturated phosphatidylcholines and ATP production in alveolar type II cells.

Ma-JY; LaCagnin-LB; Bowman-L; Miles-PR
Biochim Biophys Acta 1989 Jun; 1003(2):136-144
The effects of carbon-tetrachloride (56235) (CCl4) on surfactant disaturated phosphatidylcholine (DSPC) synthesis and ATP production was investigated in-vitro in alveolar type-II cells isolated from male Sprague-Dawley-rats. Alveolar cells were incubated in the presence or absence of CCl4 at concentrations up to 10 microliters/milliliter (microl/ml) for 1 hour, and incubated with radiolabeled choline, palmitic-acid, glycerol, or glucose as substrate for 2 to 4 hours. CCl4 inhibited choline incorporation into DSPC by 60 percent at 5microl/ml and by 90 percent at 10microl/ml. Similar results were obtained for incorporation of palmitate and glycerol. CCl4 at 5microl/ml also inhibited incorporation of labeled glycerol and glucose into surfactant phosphatidylcholine and phosphatidylglycerol. Type-II cells were incubated with or without CCl4 at concentrations up to 5microl/ml for 15 minutes, and the ATP content of the cells was determined. Intracellular ATP was decreased in a dose dependent manner, with 95 percent reduction at 5microl/ml CCl4. Oxygen consumption was decreased in a concentration dependent manner. Uptake of radiolabeled 3-O-methylglucose was reduced by 40 to 50 percent. Glucose utilization and pyruvate production were reduced by 40 percent and 80 percent respectively. The rate of ATP synthesis in isolated mitochondria was also decreased in a concentration dependent manner. CCl4 was found to decrease the activity of the mitochondrial enzyme complex involved in the synthesis of ATP. The authors conclude that CCl4 inhibits pulmonary surfactant phospholipid synthesis in alveolar type-II cells due to a dramatic reduction in the cellular levels of ATP.
NIOSH-Author; In-vitro-studies; Alveolar-cells; Laboratory-animals; Lung-cells; Organic-solvents; Organo-chlorine-compounds; Toxic-effects; Metabolic-study
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Biochimica et Biophysica Acta