Abstract
Objective To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) on the postnatal lung development in newborn rats. Methods A total of 60 newborn Sprague–Dawley rats (weighing 5.0-8.0 g) in five age groups were studied in the first experiment. The rats were divided based on the different postnatal ages: postnatal day (PND)1, PND4, PND7 and PND14. A total of 45 newborn Sprague–Dawley rats (weighing 5.0-8.0 g) were randomly divided into three groups according to the dosage of DEHP administered in the second experiment. The newborn rats were administered DEHP through intraperitoneal injection at 10 (low-dose subgroup), 100 (medium-dose subgroup ) or 750 ( high-dose subgroup) mg/kg daily from PND1 to PND13. The rats were sacrificed on PND14. Pups were sacrificed with lethal dose injection of pentobarbital sodium. The lung was removed. The right middle lobes were used for analysis. The tissue was processed for histology and lung sections were stained with HE for light microscopic (LM) morphometric measurement. The analysis was performed by means of a digital image analysis system, including pulmonary interstitial area ratio (IAR) and total length density of all segments. One-way ANOVA, LSD and Dunnet T3 methods were used for statistical analysis. Results In the normal controls, IAR decreased significantly by (31.97±5.03) %, (30.05±3.57) %, (25.33±1.83) % and (22.01±2.19) %, respectively, from PND1 to PND14 (P<0.05 or P<0.01). IAR in medium- and high-dose subgroups increased significantly by (24.11±2.78)% and (26.53±3.42)%, respectively on PND14. The total length density of all segments in unit area lung volume increased significantly by 0.047 8±0.003 7, 0.050 0±0.002 9, 0.071 2±0.003 0 and 0.084 4±0.004 3, respectively from PND1 to PND14 (P<0.01). In the DEHP treated animals, when compared with the control group, IAR was significantly higher on PND14 (P<0.05 or P<0.01), while the total length density of all segments in unit area lung volume was significantly decreased (P<0.05 or P<0.01). Length density in medium-and high-dose subgroups were higher than that of low-dose subgroup by 0.082 9±0.001 8, 0.077 2±0.002 0 and 0.071 3±0.003 7, respectively on PND14 (P<0.05 or P<0.01). Conclusions Medium- and high-dose DEHP affect the postnatal lung development in rats in a dose-dependent mode. Key words: Lung; Growth and development; Image Processing, computer-assisted; Diethylhexyl phthalate; Rats
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