Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations

The possible effects of multigenerational administration of sodium uoride (NaF) via drinking water on lung tissue morphology and biochemistry and body and lung weight were investigated in second‐generation adult male rats. For this purpose we selected 45 Albino adult Wistar rats in nine cages, each of which consisted of four females and one male. Twenty‐eight pregnant rats were selected for the experiment, divided into four groups of seven rats given 1 (control group), 10, 50 and 100 mg l −1 NaF in drinking water during the gestation period. After gestation the rats had 165 pups in total. The mothers received uoridated water during the lactation period and the offspring of the rst generation had access to uoridated water during the suckling period (21 days) and after the weaning period (30 days) until they became mature and at the start of the second part of the experiment. During this time 23 pups died and 79 female and 63 male rst‐generation rats survived. These rst‐generation rats were then used to obtain the second‐generation offspring in the same manner as before, which were subjected to the same treatments. At the end of 6 months the rats were sacriced and autopsied. Serum uoride levels and the activities of principal antioxidant enzymes were determined in lung tissue samples taken from all groups. In addition, the lung tissues were submitted for histopathological examination. Histological ndings showed alveolar congestion, alveolar cell hyperplasia and necrosis, prominent alveolar septal vessels, epithelial desquamation and macrophages in the alveolar spaces in the experimental groups. Additionally, there were inammatory inltrations in peribronchial, perivascular, intraparenchymal and respiratory tract lumen; intraparenchymal hyperaemic vessels; respiratory epithelial desquamation and proliferation; intraparenchymal thick valled vessels; parenchymal brosis; bronchiolitis; pneumonic and focal emphysematous areas. Furthermore, the lung parenchyma was observed to have a distorted appearance with loss of alveolar architecture. These histopathological ndings were more pronounced for the rat groups of 50 and 100 mg l −1 uoride. No signicant histopathological changes were observed in the rats of the control group. The increased activities of superoxide dismutase (SOD) and reduced glutathione peroxidase (GSH‐Px) and the decreased activity of catalase (CAT) in the lung tissues with 10 mg l −1 uoride might indicate activation of the antioxidant defence mechanism. The decrease in SOD, GSH‐Px and CAT activities with 50 and 100 mg l −1 uoride and the increase in thiobarbituric acid‐reactive substance levels might be related to oxidative damage that occurred in the lung. This multigenerational evaluation of the long‐term effect of different doses of uoride intake through drinking water on lung damage shows that the lung tissues were damaged, there was emphysema and inammation of lung parenchyma associated with loss of alveolar architecture and the degree of lung damage seemed to correlate with the increased dosage of uoride. A similar relationship was observed between the degree of lung damage, body and lung weight and serum uoride levels according to the uoride dose. Therefore, these results contribute to a better understanding of chronic uoride toxicity in lung tissue of second‐generation rats, especially via drinking water, and the biochemical ndings were in agreement with histological observations. In addition, increased uoride concentration did not affect reproduction or the number of pups dying but the body weight and lung weight ratios were affected by the high dose of uoride in a dose‐related pattern. Copyright © 2003 John Wiley & Sons, Ltd.