Protocatechuic acid methyl ester modulates fluoride induced pulmonary toxicity in rats

We have found that protocatechuic acid methyl ester (PCAME) attenuates fluoride (F^-) toxicity in lung epithelial cells (A549). However, this finding has to be confirmed with in vivo studies. Further, the effect of PCAME on F^- induced pulmonary fibrosis and inflammation remains limited. Hence, the present study is aimed to determine the protective effect of PCAME against F^- induced pulmonary toxicity in female albino Wistar rats. The animals were treated with sodium fluoride (NaF, 300 ppm in drinking water ad libitum) alone or in combination with PCAME (25 or 50 mg/kg bw/day by oral intubation) for 60 days and analyzed for changes in lung histology, oxidative stress, inflammation, apoptosis and fibrosis markers. PCAME supplementation prevented the F^- induced changes in the above markers. Also, altered serum and bronchoalveolar lavage fluid markers and lung histoarchitecture were also restored by PCAME. F^- induced modulations in oxidative stress markers, TUNEL positive cells and mRNA levels of inflammatory genes further normalized by PCAME in lung tissues. These results revealed that PCAME effectively attenuated the F^- induced changes in the rat lungs by reducing cellular F^- accumulation and enhancing antioxidants level. Thus PCAME can be used as a nutraceutical agent for F^- toxicity.