Abstract
Fluorosis (fluoride toxicity) seems to be reduced by plant secondary metabolites. Tamarind seed coat extract (TSCE), a mixture of procyanidins and polyphenols, possesses numerous pharmacological activities. Regardless of its beneficial properties, the underlying molecular mechanism against chronic fluorosis in vivo is not known. Hence, the present study is aimed to investigate the efficacy of TSCE against fluoride (F−)-induced pulmonary toxicity in rats. Female Wistar rats were randomly divided into four groups and treated with NaF (300 ppm in drinking water) and TSCE (100 mg/kg/bw by oral intubation) alone and in combination daily for 30 days. The results showed that F− exposure-induced modifications in lung injury markers in both serum and BALF were restored by TSCE supplementation. Additionally, F−-induced changes in oxidative stress (NOX4 and p38α MAPK), inflammation (NF-κB, COX-2, and HO-1), apoptosis (Hsp27, Hsp60, caspase3p20, and PARP1), and fibrosis (TGF-β1, psmad3, Col1αl, and hydroxyproline level) markers in the lungs were modulated by TSCE. Thus, TSCE offers protection against F−-induced pulmonary inflammation and fibrosis in rats.
Similar content being viewed by others
Abbreviations
- NaF:
-
Sodium fluoride
- F− :
-
Fluoride
- ROS:
-
Reactive oxygen species
- TSCE:
-
Tamarind seed coat extract
- BALF:
-
Bronchoalveolar lavage fluid
- NOX4:
-
NADPH oxidase 4
- MAPK:
-
Mitogen-activated protein kinase
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cell
- COX-2:
-
Cyclooxygenase 2
- HSP:
-
Heat shock protein
- HO1:
-
Heme oxygenase1
- Col:
-
Collagen
- PPI:
-
Protein permeability index
- TGFβ1:
-
Transforming growth factor beta1
- PARP1:
-
Poly(ADP) ribose polymerase1
References
Oncu, M., K. Gulle, E. Karaoz, F. Gultekin, S. Karaoz, I. Karakoyun, and E. Mumcu. 2006. Effect of chronic fluorosis on lipid peroxidation and histology of lung tissues in first and second generation rats. Toxicology and Industrial Health. 22: 375–380.
Barbier, O., L. Arreola-Mendoza, and L.M. Del Razo. 2010. Molecular mechanisms of fluoride toxicity. Chemico Biological Interactions.188:319–333. https://doi.org/10.1016/j.cbi.2010.07.011.
Knaus, R.M., F.N. Dost, D.E. Johnson, and C.H. Wang. 1976. Fluoride distribution in rats during and after continuous infusion of Na18F. Toxicology and Applied Pharmacology 38: 335–343. https://doi.org/10.1016/0041-008X(76)90140-X.
Tylenda, C.A. 2011. Toxicological profile for fluorides, hydrogen fluoride, and fluorine (update), 96. Collingdale: DIANE Publishing.
Sjogren, B. 2004. Fluoride exposure and respiratory symptoms in welders. International Journal of Occupational and Environmental Health 10: 310–312.
Viragh, E., H. Viragh, J. Laczka, and V. Coldea. 2006. Health effects of occupational exposure to fluoride and its compounds in a small-scale enterprise. Industrial Health 44: 64–68.
Van Rooy, F.G., R. Houba, H. Stigter, V.A. Zaat, M.M. Zengeni, J.M. Rooyackers, et al. 2011. A cross-sectional study of exposures, lung function and respiratory symptoms among aluminium cast-house workers. Occupational and Environmental Medicine 68: 876–882. https://doi.org/10.1136/oem.2010.062349.
Ameeramja, J., and E. Perumal. 2017. Pulmonary fluorosis: a review. Environmental Science and Pollution Research 24: 22119. https://doi.org/10.1007/s11356-017-9951-z.
Mandal, A., S. Ray, S.K. Mandal, T. Roy, R. Mallik, and D. Deoghuria. 2014. A study on spirometric evaluation of lung volume restriction in prediagnosed cases of skeletal fluorosis. Journal of Evolution of Medical and Dental Science 3: 7558–7562. https://doi.org/10.14260/jemds/2014/2935.
Ridley, W., and M. Matsuoka. 2009. Fluoride-induced cyclooxygenase-2 expression and prostaglandin E2 production in A549 human pulmonary epithelial cells. Toxicology Letters 188: 180–185. https://doi.org/10.1016/j.toxlet.2009.04.007.
Refsnes, M., T. Skuland, M. Lag, P.E. Schwarze, J. Ovrevik, and J. 2014. Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells. Journal of Inflammation Research 7: 169–185. https://doi.org/10.2147/JIR.S69646.
Ameeramja, J., L. Panneerselvam, V. Govindarajan, S. Jeyachandran, V. Baskaralingam, and E. Perumal. 2016. Tamarind seed coat ameliorates fluoride induced cytotoxicity oxidative stress, mitochondrial dysfunction and apoptosis in A549 cells. Journal of Hazardous Materials 301: 554–565. https://doi.org/10.1016/j.jhazmat.2015.09.037.
Barqaqli, E., C. Olivieri, D. Bennett, A. Prasse, J. Muller-Quernheim, and P. Rottoli. 2009. Oxidative stress in the pathogenesis of diffuse lung diseases: a review. Respiratory Medicine 103: 1245–1256. https://doi.org/10.1016/j.rmed.2009.04.014.
Wynn, T.A. 2011. Integrating mechanisms of pulmonary fibrosis. The Journal of Experimental Medicine 208: 1339–1350. https://doi.org/10.1084/jem.20110551.
Hecker, L., R. Vittal, T. Jones, R. Jagirdar, T.R. Luckhardt, J.C. Horowitz, et al. 2009. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nature Medicine 15: 1077–1081. https://doi.org/10.1038/nm.2005.
Wheeler, D.S., and H.R. Wong. 2007. The heat shock response and acute lung injury. Free Radical Biology and Medicine 42: 1–14. https://doi.org/10.1016/j.freeradbiomed.2006.08.028.
Kanagaraj, V.V., L. Panneerselvam, V. Govindarajan, J. Ameeramja, and E. Perumal. 2015. Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: a possible mechanism. BioFactors 41: 90–100. https://doi.org/10.1002/biof.1203.
Ranjan, R., D. Swarup, R.C. Patra, and V. Chandar. 2009. Tamarindus indica L and Moringa oleifera M extract administration ameliorates fluoride toxicity in rabbits. Indian Journal of Experimental Biology 47: 900–905.
Ekambaram, P., N. Thomas, S. Aruljothi, S. Bhuvaneshwari, D. Vasanth, and M. Saravanakumar. 2010. Therapeutic efficacy of Tamarindus indica (L.) to protect against fluoride-induced oxidative stress in the liver of female rats. Fluoride 43: 134–140.
Komutarin, T., S. Azadi, L. Butterworth, D. Keil, B. Chitsomboon, M. Suttajit, and B.J. Meade. 2004. Extract of the seed coat of Tamarindus indica inhibits nitric oxide production by murine macrophages in vitro and in vivo. Food and Chemical Toxicology 42: 649–658. https://doi.org/10.1016/j.fct.2003.12.001.
Sivasankar, V., S. Rajkumar, S. Murugesh, and A. Darchen. 2012. Tamarind (Tamarindus indica) fruit shell carbon: a calcium-rich promising adsorbent for fluoride removal from groundwater. Journal of Hazardous Materials 225: 164–172. https://doi.org/10.1016/j.jhazmat.2012.05.015.
Murugan, M., and E. Subramanian. 2006. Studies on defluoridation of water by tamarind seed, an unconventional biosorbent. Journal of Water and Health 4: 453–461.
Aengwanich, W., and M. Suttajit. 2013. Effect of polyphenols extracted from tamarind (Tamarindus indica L.) seed coat on pathophysiological changes and red blood cell glutathione peroxidase activity in heat-stressed broilers. International Journal of Biometeorology 57: 137–143. https://doi.org/10.1007/s00484-012-0540-z.
Reddy, G.K., and C.S. Enwemeka. 1996. A simplified method for the analysis of hydroxyproline in biological tissues. Clinical Biochemistry. 29: 225–229.
Aydin, G., E. Cicek, M. Akdogan, and O. Gokalp. 2003. Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations. Journal of Applied Toxicology. 23: 437–446. https://doi.org/10.1002/jat.935.
Anilkumar, N., R. Weber, M. Zhang, A. Brewer, and A.M. Shah. 2008. Nox4 and Nox2 NADPH Oxidases Mediate Distinct Cellular Redox Signaling Responses to Agonist Stimulation. Arteriosclerosis, Thrombosis, and Vascular Biology. 28: 1347–1354. https://doi.org/10.1161/ATVBAHA.108.164277.
Chen, Q., Z. Wang, Y. Xiong, X. Zou, and Z. Liu. 2010. Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels. International Journal of Hygiene and Environmental Health. 213: 381–386. https://doi.org/10.1016/j.ijheh.2010.06.002.
Tsuda, T., M. Watanabe, K. Ohshima, A. Yamamoto, S. Kawakishi, and T. Osawa. 1994. Antioxidative components isolated from the seed of tamarind (Tamarindus indica L.). Journal of Agricultural and Food Chemistry. 42: 2671–2674. https://doi.org/10.1021/jf00048a004.
El-Khouly, D., D. El-Bakly, A.S. Awad, H.O. El-Messalamy, and El-Demerdash. 2012. Thymoquinone blocks lung injury and fibrosis by attenuating Bleomycin induced oxidative stress and activation of nuclear factor Kappa-B in rats. Toxicology. 302: 106–113. https://doi.org/10.1016/j.tox.2012.09.001.
Gao, M., L. Chen, H. Yu, Q. Sun, J. Kou, and B. Yu. 2013. Diosgenin down-regulates NF-κB p65/p50 and p38MAPK pathways and attenuates acute lung injury induced by lipopolysaccharide in mice. International Immunopharmacology. 15: 240–245. https://doi.org/10.1016/j.intimp.2012.11.019.
Lappi-Blanco, E., R. Kaarteenaho-Wiik, P.K. Maasilta, S. Anttila, P. Paakko, and J.W. Henrik. 2006. COX-2 is widely expressed in metaplastic epithelium in pulmonary fibrous disorders. American Journal of Clinical Pathology. 126: 717–724. https://doi.org/10.1309/PFGX-CLNG-2N17-PJX9.
Fredenburgh, L.E., M.A. Perrella, and S.A. Mitsialis. 2007. The Role of Heme Oxygenase-1 in Pulmonary Disease. American Journal of Respiratory Cell and Molecular Biology. 36: 158–165. https://doi.org/10.1165/rcmb.2006-0331TR.
Zhang, M., T. Xia Wang, and P. He. 2008. Effects of fluoride on DNA damage. S-phase cell-cycle arrest and the expression of NF-kB in primary cultured rat hippocampal neurons. Toxicology Letters. 179: 1–5. https://doi.org/10.1016/j.toxlet.2008.03.002.
Thangapandiyan, S., and S. Miltonprabu. 2014. Epigallocatechin gallate supplementation protects againstrenal injury induced by fluoride intoxication in rats: Role of Nrf2/HO-1 signaling. Toxicology Reports. 1: 12–30. https://doi.org/10.1016/j.toxrep.2014.01.002.
Ameeramja, J., and E, Perumal. 2017. Protocatechuic acid methyl ester ameliorates fluoride toxicity in A549 cells. Food and Chemical Toxicology. 109 (2):941-950. https://doi.org/10.1016/j.fct.2016.12.024.
Uhal, B.D. 2008. The role of apoptosis in pulmonary fibrosis. European Respiratory Reviews. 17: 138–144. https://doi.org/10.1183/09059180.00010906.
Bonniaud, P., P.J. Margetts, K. Ask, K. Flanders, K., J. Gauldie, and M. Kolb. 2005. TGF-β and Smad3 Signaling Link Inflammation to Chronic Fibrogenesis. Journal of Immunology. 175:5390-5395.
Yang, W.H., M.Y. Kuo, C.M. Liu, Y.T. Deng, H.H. Chang, and J.Z. Chang. 2013. Curcumin inhibits TGFβ1-induced CCN2 via Src, JNK, and Smad3 in gingiva. Journal of Dental Research. 92: 629–634. https://doi.org/10.1177/0022034513488139.
Acknowledgements
The authors would like to thank Mr. Vimal and Mr. Lakshmikanthan for their valuable guidance in animal handling and treatment procedures.
Funding
This work was supported by the University Grants Commission - Major Research Project F. No. 37-94/2009 (SR) and Department of Science and Technology (DST-SERB; F. No. EMR/2014/000600), New Delhi, India.
Author information
Authors and Affiliations
Contributions
JA carried out the experimental procedures while PE helped in experimental design and manuscript preparation.
Corresponding author
Ethics declarations
The study was conducted in accordance with the ethical norms approved by the institutional animal ethical committee (Approval No: 722/02/CPCSEA).
Conflict of Interest
The authors declare that there are no conflicts of interest.
Electronic supplementary material
ESM 1
(DOC 81 kb)
Rights and permissions
About this article
Cite this article
Ameeramja, J., Perumal, E. Possible Modulatory Effect of Tamarind Seed Coat Extract on Fluoride-Induced Pulmonary Inflammation and Fibrosis in Rats. Inflammation 41, 886–895 (2018). https://doi.org/10.1007/s10753-018-0743-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-018-0743-5