Effect of lung, liver, and kidney toxicants on respiratory rate in the mouse.
The intraperitoneal administration of either butylated hydroxytoluene (BHT) +/- thoracic X-irradiation, or cyclophosphamide, and intravenous injection of oleic acid, resulted in lung injury and repair in BALB/c mice which could be assessed in unanesthetized animals by changes in respiratory rate (RR) using a total body plethysmograph. Studies with BHT +/- X-rays, and cyclophosphamide found that the RR right before sacrifice (2 weeks after BHT and 3 weeks after cyclophosphamide) correlated well (r = 0.19) with the degree of pulmonary fibrosis as measured by changes in hydroxyproline content. However, prior to this timepoint, there was a peak and trough in respiratory rate response that could not be correlated with the time course of fibrosis development in the BHT-X-ray model. In an effort to determine the influence of pulmonary edema and lung cell proliferation on respiratory rate changes, an agent (oleic acid) capable of producing lung injury followed by a high level of cellular proliferation with only minimal development of fibrosis was studied. These studies showed that good correlations were found on day 3 following injection (day of peak increase in respiratory rate) between respiratory rate and either lung wet weight (r = 0.81) or the degree of cellular proliferation as measured by the incorporation of thymidine into pulmonary DNA (r = 0.80). Liver (carbon tetrachloride) and kidney (mercuric chloride) toxicants, and starvation produced decreases or no change in RR.
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000528:radiation effects; D008099:Liver / Q000187:drug effects* / Q000528:radiation effects; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D019301:Oleic Acid; D009829:Oleic Acids / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D012119:Respiration / Q000187:drug effects*; D013217:Starvation / Q000503:physiopathology
D009829:Oleic Acids; D002084:Butylated Hydroxytoluene; D019301:Oleic Acid; D008627:Mercuric Chloride; D003520:Cyclophosphamide; D004247:DNA; D002251:Carbon Tetrachloride; D008628:Mercury