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Treatment with ferulic acid to rats with streptozotocin-induced diabetes: effects on oxidative stress, pro-inflammatory cytokines, and apoptosis in the pancreatic β cell

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Abstract

In the present study, we aimed to investigate the protective effect of ferulic acid at different doses (50 mg/kg alternative day and 50 mg/kg daily) on diabetic rats and to explore the interrelationship between oxidative stress and cytokines correlates with apoptotic events in pancreatic tissue. Male Wistar rats were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Ferulic acid was administered orally for 8 weeks. At the end of the study, all animals were sacrificed. Blood samples were collected for the biochemical estimations and pancreas was isolated for antioxidant status, histopathological, immunohistochemical, and apoptotic studies. Treatment with ferulic acid to diabetic rats significantly improved blood glucose, serum total cholesterol, triglycerides, creatinine, urea, and albumin levels toward normal. Furthermore, decrement of the elevated lipid peroxidation levels and increment of the reduced superoxide dismutase, catalase, and reduced glutathione enzyme activities in pancreatic tissues were observed in ferulic acid-treated groups. Ferulic acid-treated rats in the diabetic group showed an improved histological appearance. Our data also revealed a significant reduction in the activity of apoptosis using terminal dUTP nick end-labeling and reduced expression of TGF-β1 and IL-1β in the pancreatic β-cell of ferulic acid-treated rats. Treatment with ferulic acid daily doses produced a significant result compared to alternative dose. Collectively our results suggested that ferulic acid acts as a protective agent in diabetic rats by altering oxidative stress, expression of pro-inflammatory cytokines and apoptosis.

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References

  1. I. Celik, E. Yegin, F. Odabasoglu, Effect of experimental diabetes mellitus on plasma lactate dehydrogenase and glutamic oxaloacetic transaminase levels in rabbits. Turk. J. Biol. 26, 151–154 (2002)

    CAS  Google Scholar 

  2. M. Brownlee, Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820 (2001). doi:10.1038/414813a

    Article  PubMed  CAS  Google Scholar 

  3. K. Pyorala, M. Laakso, M. Uusitupa, Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab. Rev. 3(2), 463–524 (1987). doi:10.1002/dmr.5610030206

    Article  PubMed  CAS  Google Scholar 

  4. E.Y. Sozmen, B. Sozmen, Y. Delen, T. Onat, Catalase/superoxide dismutase (SOD) and catalase/paroxonase (PON) ratios may implicate poor glycemic control. Arch. Med. Res. 32, 283–287 (2001)

    Article  PubMed  CAS  Google Scholar 

  5. C. Wang, Y. Guan, J. Yang, Cytokines in the progression of pancreatic β-cell dysfunction. Int. J. Endocrinol. (2010). doi:10.1155/2010/515136

    PubMed  Google Scholar 

  6. S.K. Kim, M. Hebrok, Intercellular signals regulating pancreas development and function. Genes Dev. 15(2), 111–127 (2001). doi:10.1101/gad.859401

    Article  PubMed  CAS  Google Scholar 

  7. S.K. Kim, R.J. MacDonald, Signaling and transcriptional control of pancreatic organogenesis. Curr. Opin. Genet. Dev. 12, 540–547 (2002). doi:10.1016/S0959-437X(02)00338-6

    Article  PubMed  CAS  Google Scholar 

  8. S.G. Rane, J.H. Lee, H.M. Lin, Transforming growth factor-β pathway: role in pancreas development and pancreatic disease. Cytokine Growth Factor Rev. 17, 107–119 (2006). doi:10.1016/j.cytogfr.2005.09.003

    Article  PubMed  CAS  Google Scholar 

  9. D.T. Finegood, L. Scaglia, S. Bonner-Weir, Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 44, 249–256 (1995)

    Article  PubMed  CAS  Google Scholar 

  10. S. Roy, A.K. Mondru, S.K. Dontamalla, R.P. Vaddepalli, S. Sannigrahi, P.R. Veerareddy, Methoxy VO–salen stimulates pancreatic β cell survival by upregulation of eNOS and downregulation of apoptosis in STZ-induced diabetic rats. Biol. Trace Elem. Res. (2011). doi:10.1007/s12011-011-9139-1

    Google Scholar 

  11. N.T.L. Chigorimbo-Murefua, R. Sergio, S.G. Burton, Lipase catalysed synthesis of esters of ferulic acid with natural compounds and evaluation of their antioxidant properties. J. Mol. Catal. B 56(4), 277–282 (2009). doi:10.1016/j.molcatb.2008.05.017

    Article  Google Scholar 

  12. B.M. Thyagaraju, Muralidhara, Ferulic acid supplements abrogate oxidative impairments in liver and testis in the streptozotocin-diabetic rat. Zool. Sci. 25(8), 854–860 (2008)

    Article  PubMed  CAS  Google Scholar 

  13. H. Ohkawa, N. Ohishi, K. Yagi, Assay for lipid peroxides in animal tissue by thiobarbituric reaction. Anal. Biochem. 95(2), 351–358 (2004). doi:10.1016/0003-2697(79)90738-3

    Article  Google Scholar 

  14. R. Kakkar, V.S. Mantha, J. Radhi, K. Prasad, J. Kalra, Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin. Sci. 94, 623–632 (1998)

    PubMed  CAS  Google Scholar 

  15. R. Kakkar, J. Kalra, S.V. Mantha, K. Prasad, Lipid peroxidation and antioxidant enzyme activity in streptozotocin-induced Fischer rats. Mol. Cell. Biochem. 151, 113–119 (1995)

    Article  PubMed  CAS  Google Scholar 

  16. R. Balaraman, P.A. Bafna, S.A. Kolhapure, Antioxidant activity of DHC-1—a herbal formulation. J. Ethnopharmacol. 94, 135–141 (2004). doi:10.1016/j.jep.2004.05.008

    Article  PubMed  CAS  Google Scholar 

  17. K. Srinivasan, P. Ramarao, Animal models in type 2 diabetes research: an overview. Indian J. Med. Res. 125, 451–472 (2007)

    PubMed  CAS  Google Scholar 

  18. N. Takasu, T. Asawa, I. Komiya, Y. Nagasawa, T. Yamada, Alloxan induced DNA strand breaks in pancreatic islets. Evidence for H2O2 as an intermediate. J. Biol. Chem. 266, 2112–2114 (1991)

    PubMed  CAS  Google Scholar 

  19. M. Eslnar, B. Guldbakke, M. Tiedge, R. Munday, S. Lenzen, Relative importance of transport and alkylation for pancreatic beta cells toxicity of streptozotocin. Diabetologia 43, 1528–1533 (2000). doi:10.1007/s001250051564

    Article  Google Scholar 

  20. M. Balasubashini, R. Rukkumani, V.P. Menon, Protective effects of ferulic acid on hyperlipidemic diabetic rats. Acta Diabetol. 40(3), 118–122 (2003). doi:10.1007/s00592-003-0099-6

    Article  Google Scholar 

  21. M. Ohnishi, T. Matuo, T. Tsuno, A. Hosoda, E. Nomura, H. Taniguchi, H. Sasaki, H. Morishita, Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice. BioFactors 21(1–4), 315–319 (2004). doi:10.1002/biof.552210161

    Article  PubMed  CAS  Google Scholar 

  22. J. Baynes, Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405–412 (1991). doi:10.2337/diabetes.40.4.405

    Article  PubMed  CAS  Google Scholar 

  23. A. Vincent, J. Russell, P. Low, E. Feldman, Oxidative stress in the pathogenesis of diabetic neuropathy. Endocrine Rev. 25, 612–628 (2004). doi:10.1210/er.2003-0019

    Article  CAS  Google Scholar 

  24. J.W. Baynes, S.R. Thorpe, Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48(1), 1–9 (1999). doi:10.2337/diabetes.48.1.1

    Article  PubMed  CAS  Google Scholar 

  25. P.L. Montilla, J.F. Vargas, I.F. Tunez, M.C. Munoz de Agueda, M.E. Valdelvira, E.S. Cabrera, Oxidative stress in diabetic rats induced by streptozotocin: preventive effects of melatonin. J. Pineal Res. 25, 94–100 (1998). doi:10.1111/j.1600-079X.1998.tb00545.x

    Article  PubMed  CAS  Google Scholar 

  26. M.S. Balasubashini, R. Rukkumani, P. Viswanathan, V.P. Menon, Ferulic acid alleviates lipid peroxidation in diabetic rats. Phytother. Res. 18(4), 310–314 (2004). doi:10.1002/ptr.1440

    Article  PubMed  CAS  Google Scholar 

  27. J. Fujii, Y. Iuchi, S. Matsuki, T. Ishii, Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J. Androl. 5, 231–242 (2003). doi:10.1038/aja.2008.47

    PubMed  CAS  Google Scholar 

  28. N. Lin, H. Chen, H. Zhang, X. Wan, Q. Su, Mitochondrial reactive oxygen species (ROS) inhibition ameliorates palmitate induced INS-1 beta cell death. Endocrine 42, 107–117 (2012). doi:10.1007/s12020-012-9633-z

    Article  PubMed  CAS  Google Scholar 

  29. R.G. Mirmira, Saturated free fatty acids: islet β cell “stressERs”. Endocrine 42, 1–2 (2012). doi:10.1007/s12020-012-9713-0

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge Mr. Jayanta Bhowmick for his assistance in preparing the histopathological slides. We would like to thank Mr. Lalmohon Masanta and Mr. Pravanjan Bhakta for providing the laboratory oriented research facilities.

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The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, NSHM Knowledge Campus, 124 B.L. Saha Road, Kolkata, 700053, West Bengal, India

    Souvik Roy, Satyajit Kumar Metya, Santanu Sannigrahi, Noorjaman Rahaman & Faiqa Ahmed

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  1. Souvik Roy
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  2. Satyajit Kumar Metya
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Correspondence to Souvik Roy.

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Roy, S., Metya, S.K., Sannigrahi, S. et al. Treatment with ferulic acid to rats with streptozotocin-induced diabetes: effects on oxidative stress, pro-inflammatory cytokines, and apoptosis in the pancreatic β cell. Endocrine 44, 369–379 (2013). https://doi.org/10.1007/s12020-012-9868-8

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