Skip to main content
Top
Published in: Inflammation 4/2018

01-08-2018 | ORIGINAL ARTICLE

Protective Effect of Apigenin on Acrylonitrile-Induced Inflammation and Apoptosis in Testicular Cells via the NF-κB Pathway in Rats

Authors: Yuhui Dang, Zhilan Li, Qian Wei, Ruiping Zhang, Hongli Xue, Yingmei Zhang

Published in: Inflammation | Issue 4/2018

Login to get access

Abstract

Apigenin (AP) as a plant flavonoid is found to attenuate acrylonitrile (ACN) toxicity by reducing ROS production and inhibiting apoptosis. Therefore, the present study aimed to evaluate the role of AP on ACN-induced inflammation and apoptosis in germ cells and whether it is through the NF-κB signaling pathway. AP increased the concentrations of lactate dehydrogenase isozyme (LDH) and sorbitol dehydrogenase (SDH), while the concentrations of interleukin β (IL-1β), tumor-necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly reduced. AP could downregulate the expression of the nuclear factor of kappa B (NF-κB) and inhibit phosphorylation of the inhibitory κBα (IκBα). Cleaved caspase-3 was also upregulated by AP, and the apoptotic were less than those in the ACN group. These results suggest that AP might improve maturation and energy metabolism of testes, inhibit NF-κB activation. Then AP could further downregulate NF-κB signal and inhibit the germ cell apoptosis and reduce inflammatory caused by ACN.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sleiman, M., J.M. Logue, W. Luo, J.F. Pankow, L.A. Gundel, and H. Destaillats. 2014. Inhalable constituents of thirdhand tobacco smoke: chemical characterization and health impact considerations. Environmental Science & Technology 48 (22): 13093–13101.CrossRef Sleiman, M., J.M. Logue, W. Luo, J.F. Pankow, L.A. Gundel, and H. Destaillats. 2014. Inhalable constituents of thirdhand tobacco smoke: chemical characterization and health impact considerations. Environmental Science & Technology 48 (22): 13093–13101.CrossRef
2.
go back to reference Abe, Y., M. Yamaguchi, M. Mutsuga, Y. Kawamura, and H. Akiyama. 2014. Survey of volatile substances in kitchen utensils made from acrylonitrile-butadiene-styrene and acrylonitrile-styrene resin in Japan. Food Science & Nutrition 2 (3): 236–243.CrossRef Abe, Y., M. Yamaguchi, M. Mutsuga, Y. Kawamura, and H. Akiyama. 2014. Survey of volatile substances in kitchen utensils made from acrylonitrile-butadiene-styrene and acrylonitrile-styrene resin in Japan. Food Science & Nutrition 2 (3): 236–243.CrossRef
3.
go back to reference Abe, Y., M. Yamaguchi, M. Mutsuga, H. Akiyama, and Y. Kawamura. 2013. Volatile substances in polymer toys made from butadiene and styrene. American Journal of Analytical Chemistry 04 (05): 229–237.CrossRef Abe, Y., M. Yamaguchi, M. Mutsuga, H. Akiyama, and Y. Kawamura. 2013. Volatile substances in polymer toys made from butadiene and styrene. American Journal of Analytical Chemistry 04 (05): 229–237.CrossRef
4.
go back to reference Caito, S.W., Y. Yu, and M. Aschner. 2014. Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia. Neurotoxicology 42: 1–7.CrossRefPubMed Caito, S.W., Y. Yu, and M. Aschner. 2014. Differential inflammatory response to acrylonitrile in rat primary astrocytes and microglia. Neurotoxicology 42: 1–7.CrossRefPubMed
5.
go back to reference Li, X.J., B. Li, J.S. Huang, J.M. Shi, P. Wang, W. Fan, and Y.L. Zhou. 2014. Effects of acrylonitrile on lymphocyte lipid rafts and RAS/RAF/MAPK/ERK signaling pathways. Genetics and Molecular Research 13 (3): 7747–7756.CrossRefPubMed Li, X.J., B. Li, J.S. Huang, J.M. Shi, P. Wang, W. Fan, and Y.L. Zhou. 2014. Effects of acrylonitrile on lymphocyte lipid rafts and RAS/RAF/MAPK/ERK signaling pathways. Genetics and Molecular Research 13 (3): 7747–7756.CrossRefPubMed
6.
go back to reference Hamdy, N.M., F.A. Al-Abbasi, H.A. Alghamdi, M.F. Tolba, A. Esmat, and A.B. Abdel-Naim. 2012. Role of neutrophils in acrylonitrile-induced gastric mucosal damage. Toxicology Letters 208 (2): 108–114.CrossRefPubMed Hamdy, N.M., F.A. Al-Abbasi, H.A. Alghamdi, M.F. Tolba, A. Esmat, and A.B. Abdel-Naim. 2012. Role of neutrophils in acrylonitrile-induced gastric mucosal damage. Toxicology Letters 208 (2): 108–114.CrossRefPubMed
7.
go back to reference Zhong, X.J., X. Wu, Y.L. Zhou, S.X. Jin, and T.Y. Jin. 2004. Epidemiological study of the effects of acrylonitrile on male reproductive health. Occupational Health and Emergency Rescue 04: 173–177. Zhong, X.J., X. Wu, Y.L. Zhou, S.X. Jin, and T.Y. Jin. 2004. Epidemiological study of the effects of acrylonitrile on male reproductive health. Occupational Health and Emergency Rescue 04: 173–177.
8.
go back to reference Jin, S.X., X.J. Zhong, X. Wu, J.S. Huang, Z.Y. Han, and T.Y. Jin. 2005. The effect of acrylonitrile on male sex hormone levels. Industrial Health and Occupational Diseases 04: 226–231. Jin, S.X., X.J. Zhong, X. Wu, J.S. Huang, Z.Y. Han, and T.Y. Jin. 2005. The effect of acrylonitrile on male sex hormone levels. Industrial Health and Occupational Diseases 04: 226–231.
9.
go back to reference Dang, Y.H., Z.L. Li, J.J. Guo, Q.L. Zhao, J.Y. Chen, J. ZHang, and R.X. Chang. 2017. Study of repeated measurement design on effects of acrylonitrile to sex hormone in serum of male rats. Industrial Health and Occupational Diseases 02: 104–108. Dang, Y.H., Z.L. Li, J.J. Guo, Q.L. Zhao, J.Y. Chen, J. ZHang, and R.X. Chang. 2017. Study of repeated measurement design on effects of acrylonitrile to sex hormone in serum of male rats. Industrial Health and Occupational Diseases 02: 104–108.
10.
go back to reference Dang, Y.H., Z.L. Li, L. Pan, W. Li, B.Y. Luo, Q.R. Fan, and Q. Wei. 2017. Effect of acrylonitrile induced reactive oxygen species generated on sperm quality and flagella ultrastructure in rats. J Toxicol 04: 258–262. Dang, Y.H., Z.L. Li, L. Pan, W. Li, B.Y. Luo, Q.R. Fan, and Q. Wei. 2017. Effect of acrylonitrile induced reactive oxygen species generated on sperm quality and flagella ultrastructure in rats. J Toxicol 04: 258–262.
11.
go back to reference Duarte, S., D. Arango, A. Parihar, P. Hamel, R. Yasmeen, and A.I. Doseff. 2013. Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function. International Journal of Molecular Sciences 14 (9): 17664–17679.CrossRefPubMedPubMedCentral Duarte, S., D. Arango, A. Parihar, P. Hamel, R. Yasmeen, and A.I. Doseff. 2013. Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function. International Journal of Molecular Sciences 14 (9): 17664–17679.CrossRefPubMedPubMedCentral
12.
go back to reference Choudhury, D., A. Ganguli, D.G. Dastidar, B.R. Acharya, A. Das, and G. Chakrabarti. 2013. Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin. Biochimie 95 (6): 1297–1309.CrossRefPubMed Choudhury, D., A. Ganguli, D.G. Dastidar, B.R. Acharya, A. Das, and G. Chakrabarti. 2013. Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin. Biochimie 95 (6): 1297–1309.CrossRefPubMed
13.
go back to reference Haibo, L., S. Haixia, Z. Yuan, G. Guiying, Y. Qiang, G. Peng, and X. Haibin. 2011. Acute toxicity, genetic toxicity and sub-chronic toxicity of apigenin. Chinese Journal of Food Hygiene 06: 489–494. Haibo, L., S. Haixia, Z. Yuan, G. Guiying, Y. Qiang, G. Peng, and X. Haibin. 2011. Acute toxicity, genetic toxicity and sub-chronic toxicity of apigenin. Chinese Journal of Food Hygiene 06: 489–494.
14.
go back to reference Shang, X., X. Guo, F. Yang, B. Li, H. Pan, X. Miao, and J. Zhang. 2017. The toxicity and the acaricidal mechanism against Psoroptes cuniculi of the methanol extract of Adonis coerulea Maxim. Veterinary Parasitology 240: 17–23.CrossRefPubMed Shang, X., X. Guo, F. Yang, B. Li, H. Pan, X. Miao, and J. Zhang. 2017. The toxicity and the acaricidal mechanism against Psoroptes cuniculi of the methanol extract of Adonis coerulea Maxim. Veterinary Parasitology 240: 17–23.CrossRefPubMed
15.
go back to reference Chen, W.C., L.F. Liu, S. Wu, J.W. Liu, Y.H. Dang, J. Zhang, and Z.L. Li. 2014. Effects of apigenin on marked enzymes and oxidation-reduction balance in testicular of male rats. Natural Product Research and Development 10: 1580–1584. Chen, W.C., L.F. Liu, S. Wu, J.W. Liu, Y.H. Dang, J. Zhang, and Z.L. Li. 2014. Effects of apigenin on marked enzymes and oxidation-reduction balance in testicular of male rats. Natural Product Research and Development 10: 1580–1584.
16.
go back to reference Anusha, C., T. Sumathi, and L.D. Joseph. 2017. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chemico-Biological Interactions 269: 67–79.CrossRefPubMed Anusha, C., T. Sumathi, and L.D. Joseph. 2017. Protective role of apigenin on rotenone induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress mediated apoptosis. Chemico-Biological Interactions 269: 67–79.CrossRefPubMed
17.
go back to reference Seo, H.S., H.S. Choi, S.R. Kim, Y.K. Choi, S.M. Woo, I. Shin, J.K. Woo, S.Y. Park, Y.C. Shin, and S.G. Ko. 2012. Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NFκB signaling in HER2-overexpressing breast cancer cells. Molecular and Cellular Biochemistry 366 (1–2): 319–334.CrossRefPubMed Seo, H.S., H.S. Choi, S.R. Kim, Y.K. Choi, S.M. Woo, I. Shin, J.K. Woo, S.Y. Park, Y.C. Shin, and S.G. Ko. 2012. Apigenin induces apoptosis via extrinsic pathway, inducing p53 and inhibiting STAT3 and NFκB signaling in HER2-overexpressing breast cancer cells. Molecular and Cellular Biochemistry 366 (1–2): 319–334.CrossRefPubMed
18.
go back to reference Chen, X.J., M.Y. Wu, D.H. Li, and J. You. 2016. Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-κB/MMP-9. Molecular Medicine Reports 14 (3): 2352–2358.CrossRefPubMed Chen, X.J., M.Y. Wu, D.H. Li, and J. You. 2016. Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-κB/MMP-9. Molecular Medicine Reports 14 (3): 2352–2358.CrossRefPubMed
19.
go back to reference Dang, Y., Q. Zhao, B. Luo, L. Pan, Q. Wei, R. Zhang, Q. Fan, J. Chen, R. Chang, J. Zhang, and Z. Li. 2017. Effects of acrylonitrile-induced oxidative stress on testicular apoptosis through activation of NF-κB signaling pathway in male Sprague Dawley rats. American Journal of Translational Research 9 (9): 4227–4235.PubMedPubMedCentral Dang, Y., Q. Zhao, B. Luo, L. Pan, Q. Wei, R. Zhang, Q. Fan, J. Chen, R. Chang, J. Zhang, and Z. Li. 2017. Effects of acrylonitrile-induced oxidative stress on testicular apoptosis through activation of NF-κB signaling pathway in male Sprague Dawley rats. American Journal of Translational Research 9 (9): 4227–4235.PubMedPubMedCentral
20.
go back to reference Dang, Y., Z. Li, B. Luo, L. Pan, Q. Wei, and Y. Zhang. 2017. Protective effects of apigenin against acrylonitrile-induced subchronic sperm injury in rats. Food and Chemical Toxicology 109 (Pt 1): 517–525.CrossRefPubMed Dang, Y., Z. Li, B. Luo, L. Pan, Q. Wei, and Y. Zhang. 2017. Protective effects of apigenin against acrylonitrile-induced subchronic sperm injury in rats. Food and Chemical Toxicology 109 (Pt 1): 517–525.CrossRefPubMed
21.
go back to reference Wu, X., X.J. Zhong, W. Fan, Y.L. Zhou, and T.Y. Jin. 2001. Effects of acrylonitrile on reproductive function in male rats. Industrial Health and Occupational Diseases 19 (5): 40–42. Wu, X., X.J. Zhong, W. Fan, Y.L. Zhou, and T.Y. Jin. 2001. Effects of acrylonitrile on reproductive function in male rats. Industrial Health and Occupational Diseases 19 (5): 40–42.
22.
go back to reference Wu, S., W.C. Chen, L.F. Lui, J.W. Liu, R.X. Chang, J. Zhang, and Z.L. Li. 2014. Effects of apigenin on sperm quality and sex hormones in rats. Journal of Toxicology 28 (05): 385–389. Wu, S., W.C. Chen, L.F. Lui, J.W. Liu, R.X. Chang, J. Zhang, and Z.L. Li. 2014. Effects of apigenin on sperm quality and sex hormones in rats. Journal of Toxicology 28 (05): 385–389.
23.
go back to reference Gradolatto, A. 2004. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metabolism and Disposition 33 (1): 49–54.CrossRefPubMed Gradolatto, A. 2004. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metabolism and Disposition 33 (1): 49–54.CrossRefPubMed
24.
go back to reference Zhang, G.L., F. Yu, D.Z. Dai, Y.S. Cheng, C. Zhang, and Y. Dai. 2012. CPU86017-RS attenuate hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines. Acta Pharmacologica Sinica 33 (4): 470–478.CrossRefPubMedPubMedCentral Zhang, G.L., F. Yu, D.Z. Dai, Y.S. Cheng, C. Zhang, and Y. Dai. 2012. CPU86017-RS attenuate hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines. Acta Pharmacologica Sinica 33 (4): 470–478.CrossRefPubMedPubMedCentral
25.
go back to reference Yang, J., G. Wu, Y. Feng, Q. Lv, S. Lin, and J. Hu. 2010. Effects of taurine on male reproduction in rats of different ages. Journal of Biomedical Science 17 (Suppl 1): S9.CrossRefPubMedPubMedCentral Yang, J., G. Wu, Y. Feng, Q. Lv, S. Lin, and J. Hu. 2010. Effects of taurine on male reproduction in rats of different ages. Journal of Biomedical Science 17 (Suppl 1): S9.CrossRefPubMedPubMedCentral
26.
go back to reference Baker, S.J., and E.P. Reddy. 1998. Modulation of life and death by the TNF receptor superfamily. Oncogene 17 (25): 3261–3270.CrossRefPubMed Baker, S.J., and E.P. Reddy. 1998. Modulation of life and death by the TNF receptor superfamily. Oncogene 17 (25): 3261–3270.CrossRefPubMed
27.
go back to reference Dinarello, C.A. 1996. Biologic basis for interleukin-l in disease. Blood 87 (6): 2095–2147.PubMed Dinarello, C.A. 1996. Biologic basis for interleukin-l in disease. Blood 87 (6): 2095–2147.PubMed
28.
go back to reference Stephan, J.P., V. Syed, and B. Jegou. 1997. Regulation of Sertoli cell IL-1 and IL-6 production in vitro. Molecular and Cellular Endocrinology 134 (2): 109–118.CrossRefPubMed Stephan, J.P., V. Syed, and B. Jegou. 1997. Regulation of Sertoli cell IL-1 and IL-6 production in vitro. Molecular and Cellular Endocrinology 134 (2): 109–118.CrossRefPubMed
29.
go back to reference Delfino, F., and W.H. Walker. 1998. Stage-specific nuclear expression of NF-κB in mammalian testis. Molecular Endocrinology 12 (11): 1696–1707.PubMed Delfino, F., and W.H. Walker. 1998. Stage-specific nuclear expression of NF-κB in mammalian testis. Molecular Endocrinology 12 (11): 1696–1707.PubMed
30.
go back to reference Zhang, X., G. Wang, E.C. Gurley, and H. Zhou. 2014. Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One 9 (9): e107072.CrossRefPubMedPubMedCentral Zhang, X., G. Wang, E.C. Gurley, and H. Zhou. 2014. Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One 9 (9): e107072.CrossRefPubMedPubMedCentral
31.
go back to reference Brieger, K., S. Schiavone, F.J. Miller, and K.H. Krause. 2012. Reactive oxygen species: From health to disease. Swiss Medical Weekly 142: w13659.PubMed Brieger, K., S. Schiavone, F.J. Miller, and K.H. Krause. 2012. Reactive oxygen species: From health to disease. Swiss Medical Weekly 142: w13659.PubMed
32.
go back to reference Vandenberg, R., G.R.M.M. Haenen, H. van den Berg, and A. Bast. 2001. Transcription factor NF-κB as a potential biomarker for oxidative stress. The British Journal of Nutrition 86 (S1): S121–S127.CrossRef Vandenberg, R., G.R.M.M. Haenen, H. van den Berg, and A. Bast. 2001. Transcription factor NF-κB as a potential biomarker for oxidative stress. The British Journal of Nutrition 86 (S1): S121–S127.CrossRef
33.
go back to reference Baeuerlec, J.M.M.R. 1997. Study of gene regulation by NF-kB and AP-1 in response to reactive oxygen intermediates. Methods 11 (3): 301–321.CrossRef Baeuerlec, J.M.M.R. 1997. Study of gene regulation by NF-kB and AP-1 in response to reactive oxygen intermediates. Methods 11 (3): 301–321.CrossRef
34.
go back to reference Woo, E.R., Y.R. Pokharel, J.W. Yang, S.Y. Lee, and K.W. Kang. 2006. Inhibition of nuclear factor-κB activation by 2′,8″-biapigenin. Biological & Pharmaceutical Bulletin 29 (5): 976–980.CrossRef Woo, E.R., Y.R. Pokharel, J.W. Yang, S.Y. Lee, and K.W. Kang. 2006. Inhibition of nuclear factor-κB activation by 2′,8″-biapigenin. Biological & Pharmaceutical Bulletin 29 (5): 976–980.CrossRef
35.
go back to reference Kowalski, J., A. Samojedny, M. Paul, G. Pietsz, and T. Wilczok. 2005. Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1beta and tumor necrosis factor-alpha genes in J774.2 macrophages. Pharmacological Reports 57 (3): 390–394.PubMed Kowalski, J., A. Samojedny, M. Paul, G. Pietsz, and T. Wilczok. 2005. Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1beta and tumor necrosis factor-alpha genes in J774.2 macrophages. Pharmacological Reports 57 (3): 390–394.PubMed
36.
go back to reference Henkels, K.M., K. Frondorf, M.E. Gonzalez-Mejia, A.L. Doseff, and J. Gomez-Cambronero. 2011. IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3). FEBS Letters 585 (1): 159–166.CrossRefPubMed Henkels, K.M., K. Frondorf, M.E. Gonzalez-Mejia, A.L. Doseff, and J. Gomez-Cambronero. 2011. IL-8-induced neutrophil chemotaxis is mediated by Janus kinase 3 (JAK3). FEBS Letters 585 (1): 159–166.CrossRefPubMed
37.
go back to reference Nicholas, C., S. Batra, M.A. Vargo, O.H. Voss, M.A. Gavrilin, M.D. Wewers, D.C. Guttridge, E. Grotewold, and A.I. Doseff. 2007. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-κB through the suppression of p65 phosphorylation. Journal of Immunology 179 (10): 7121–7127.CrossRef Nicholas, C., S. Batra, M.A. Vargo, O.H. Voss, M.A. Gavrilin, M.D. Wewers, D.C. Guttridge, E. Grotewold, and A.I. Doseff. 2007. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-κB through the suppression of p65 phosphorylation. Journal of Immunology 179 (10): 7121–7127.CrossRef
38.
go back to reference Zhao, M., F.S. Lewis Wang, X. Hu, F. Chen, and H.M. Chan. 2017. Acrylamide-induced neurotoxicity in primary astrocytes and microglia: Roles of the Nrf2-ARE and NF-κB pathways. Food and Chemical Toxicology 106: 25–35.CrossRefPubMed Zhao, M., F.S. Lewis Wang, X. Hu, F. Chen, and H.M. Chan. 2017. Acrylamide-induced neurotoxicity in primary astrocytes and microglia: Roles of the Nrf2-ARE and NF-κB pathways. Food and Chemical Toxicology 106: 25–35.CrossRefPubMed
Metadata
Title
Protective Effect of Apigenin on Acrylonitrile-Induced Inflammation and Apoptosis in Testicular Cells via the NF-κB Pathway in Rats
Authors
Yuhui Dang
Zhilan Li
Qian Wei
Ruiping Zhang
Hongli Xue
Yingmei Zhang
Publication date
01-08-2018
Publisher
Springer US
Published in
Inflammation / Issue 4/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-018-0791-x

Other articles of this Issue 4/2018

Inflammation 4/2018 Go to the issue