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

Abstract

The possible effects of multigenerational administration of sodium fluoride (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 fluoridated water during the lactation period and the offspring of the first generation had access to fluoridated 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 first-generation rats survived. These first-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 sacrificed and autopsied. Serum fluoride 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 findings 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 inflammatory infiltrations in peribronchial, perivascular, intraparenchymal and respiratory tract lumen; intraparenchymal hyperaemic vessels; respiratory epithelial desquamation and proliferation; intraparenchymal thick walled vessels; parenchymal fibrosis; bronchiolitis; pneumonic and focal emphysematous areas. Furthermore, the lung parenchyma was observed to have a distorted appearance with loss of alveolar architecture. These histopathological findings were more pronounced for the rat groups of 50 and 100 mg l(-1) fluoride. No significant 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) fluoride might indicate activation of the antioxidant defence mechanism. The decrease in SOD, GSH-Px and CAT activities with 50 and 100 mg l(-1) fluoride 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 fluoride intake through drinking water on lung damage shows that the lung tissues were damaged, there was emphysema and inflammation of lung parenchyma associated with loss of alveolar architecture and the degree of lung damage seemed to...

Neurobehavioural effects of exposure to fluoride in the earliest stages of rat development

“…In addition, F, which is biologically active even at the lowest concentrations, can readily penetrate into cell membranes by simple diffusion and cause adverse effects on cell metabolism and function. Exposure to NaF (50, 100 mg/kg) through drinking water during gestation has resulted in histopathological changes, such as alveolar cell hyperplasia and necrosis in the lungs of rats over several generations [12]. In addition, administration of NaF (40 mg/kg) in rats during pregnancy and lactation was observed to result in hypoproteinemia and hypoglycemia in mothers and offspring [13].…”

Fluoride Toxicity and Status of Serum Thyroid Hormones, Brain Histopathology, and Learning Memory in Rats: A Multigenerational Assessment

“…The study of more than one generation allows detection not only of any effects on adult reproduction but also of effects on subsequent generations due to exposure in utero and early postnatally. The latest evaluation of sodium fluoride administration through multiple generations has been made previously in general aspects by Collins et al [18,19], in the myocardium, lung, kidney, and testis by Cicek et al [20], Aydin et al [21], Karaoz et al [22], and Meral et al [23] respectively, but brain tissue has not been studied specifically in multigeneration animals. Due to the lack of information on multigeneration studies concerning fluoride-induced changes on the thyroid hormone status, the histopathology of discrete brain regions, and the resultant alterations in acetylcholine esterase levels and the learning and memory abilities, the present study was undertaken.…”

Evaluation of Fluoride-Induced Oxidative Stress in Rat Brain: A Multigeneration Study

“…Meral et al [26] reported a significant increase in TBARS level in the testes of both first-and second-generation rats when compared to control, and the TBARS levels of second-generation rats were significantly higher than those of first-generation rats. Aydin et al [27] reported a significant increase in TBARS levels in lung tissues in groups treated with 50 and 100 mg/L fluoride over several generations. Similarly, Karaoz et al [28] showed that chronic fluorosis can lead to enhanced lipid peroxidation and kidney tissue alterations in first-and secondgeneration rats.…”