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.
Diabetes Rat pancreas Ferulic acid TGF-β1 IL-1β Apoptosis
This is a preview of subscription content, log in to check access.
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.
Conflict of interest
The authors declare that there is no conflict of interest.
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)Google Scholar
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)PubMedCrossRefGoogle Scholar
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/s12011-011-9139-1Google Scholar
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.2008.05.017CrossRefGoogle Scholar
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)PubMedCrossRefGoogle Scholar
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)PubMedGoogle Scholar
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)PubMedCrossRefGoogle Scholar
K. Srinivasan, P. Ramarao, Animal models in type 2 diabetes research: an overview. Indian J. Med. Res. 125, 451–472 (2007)PubMedGoogle Scholar
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)PubMedGoogle Scholar
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/s001250051564CrossRefGoogle Scholar
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.552210161PubMedCrossRefGoogle Scholar
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.2008.47PubMedGoogle Scholar