Abstract
The present study was undertaken to investigate whether chlorogenic acid (CGA) could protect kidney function against oxidative stress in the diabetic nephropathy (DN) rats. The treatment with CGA could decrease significantly the levels of blood glucose, blood urea nitrogen and serum creatinine in DN rats. Moreover, CGA significantly increased the activity of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, the level of lipid peroxidation malondialdehyde was reduced markedly after CGA administration. Immunohistochemical analysis also showed that CGA downregulated significantly cyclooxygenase-2 protein expression in renal tissue, which is considered as one of the major pathogeneses of oxidative stress. Furthermore, we demonstrated that CGA could block the expression of activating transcription factor-6, C/EBP homology protein and the phosphorylation of eukaryotic initiation factor 2α and double stranded RNA-activated protein kinase-like endoplasmic reticulum kinase. In addition, we attempted to detect the presence of diabetic renal tissues apoptosis-related proteins. Our data provided evidence to support this fact that CGA attenuated oxidative stress in streptozocin-induced DN rats. Its molecular mechanism may inhibit the endoplasmic reticulum-stress response in DN.
Similar content being viewed by others
References
Barati MT, Powell DW, Kechavarzi BD, Isaacs SM, Zheng S, Epstein PN, Cai L, Coventry S, Rane MJ, Klein JB (2015) Differential expression of endoplasmic reticulum stress-response proteins in different renal tubule subtypes of OVE26 diabetic mice. Cell Stress Chaperones 21:155–166
Bhatti F, Mankhey RW, Asico L, Quinn MT, Welch WJ, Maric C (2005) Mechanisms of antioxidant and pro-oxidant effects of alpha-lipoic acid in the diabetic and nondiabetic kidney. Kidney Int 67:1371–1380
Chen Y, Gui D, Chen J, He D, Luo Y, Wang N (2014) Down-regulation of PERK-ATF4-CHOP pathway by astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats. Cell Physiol Biochem 33:1975–1987
Cheng X, Zhang X, Su J, Zhang Y, Zhou W, Zhou J, Wang C, Liang H, Chen X, Shi R, Zen K (2015) miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn’s disease. Sci Rep. doi:10.1038/srep10397
Cybulsky AV, Takano T, Papillon J, Bijian K (2005) Role of the endoplasmic reticulum unfolded protein response in glomerular epithelial cell injury. J Biol Chem 280:24396–24403
Fioretto P, Mauer M (2007) Histopathology of diabetic nephropathy. Semin Nephrol 27:195–207
Ha H, Kim KH (1999) Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C. Diabetes Res Clin Pract 45:147–151
Ha H, Lee HB (2001) Oxidative stress in diabetic nephropathy: basic and clinical information. Curr Diab Rep 1:282–287
Hwang SJ, Kim YW, Park Y, Lee HJ, Kim KW (2014) Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res 63:81–90
Jin S, Chang C, Zhang L, Liu Y, Huang X, Chen Z (2015) Chlorogenic acid improves late diabetes through adiponectin receptor signaling pathways in db/db mice. PLoS One. doi:10.1371/journal.pone.0120842
Kadowaki H, Nishitoh H (2013) Signaling pathways from the endoplasmic reticulum and their roles in disease. Genes (Basel) 4:306–333
Kanno Y, Watanabe R, Zempo H, Ogawa M, Suzuki J, Isobe M (2013) Chlorogenic acid attenuates ventricular remodeling after myocardial infarction in mice. Int Heart J 54:176–180
Kedziora KK, Szram S, Kornatowski T, Szadujkis-Szadurski L, Kedziora J, Bartosz G (2003) Effect of vitamin E and vitamin C supplementation on antioxidative state and renal glomerular basement membrane thickness in diabetic kidney. Nephron Exp Nephrol 95:134–143
Kono Y, Kobayashi K, Tagawa S, Adachi K, Ueda A, Sawa Y, Shibata H (1997) Antioxidant activity of polyphenolics in diets. Rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen. Biochim Biophys Acta 1335:335–342
Lee EA, Seo JY, Jiang Z, Yu MR, Kwon MK, Ha H, Lee HB (2005) Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney. Kidney Int 67:1762–1771
Lin P, Yang Y, Li X, Chen F, Cui C, Hu L, Li Q, Liu W, Jin Y (2012) Endoplasmic reticulum stress is involved in granulosa cell apoptosis during follicular atresia in goat ovaries. Mol Reprod Dev 79:423–432
Liu Z, Lv Y, Zhao N, Guan G, Wang J (2015) Protein kinase R-like ER kinase and its role in endoplasmic reticulum stress-decided cell fate. Cell Death Dis. doi:10.1038/cddis.2015.183
Luo ZF, Feng B, Mu J, Qi W, Zeng W, Guo YH, Pang Q, Ye ZL, Liu L, Yuan FH (2010) Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: regulation of endoplasmic reticulum stress-oxidative activation. Toxicol Appl Pharmacol 246:49–57
Madhusudhan T, Wang H, Dong W, Ghosh S, Bock F, Thangapandi VR, Ranjan S, Wolter J, Kohli S, Shahzad K, Heidel F (2015) Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy. Nat Commun. doi:10.1038/ncomms7496
Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9:2277–2293
Nishi, Ahad A, Kumar P (2013) A protective effect of chlorogenic acid against diabetic nephropathy in high fat diet/streptozotocin induced type-2 diabetic rats. Int J Pharm Sci 5:489–495
Park Y, Kim H, Park L, Min D, Park J, Choi S, Park MH (2015) Effective delivery of endogenous antioxidants ameliorates diabetic nephropathy. PLoS One. doi:10.1371/journal.pone.0130815
Pourghasem M, Shafi H, Babazadeh Z (2015) Histological changes of kidney in diabetic nephropathy. Casp J Intern Med 6:120–127
Sun XB, Lu HE, Chen Y, Fan XH, Tong B (2014) Effect of lithium chloride on endoplasmic reticulum stress-related PERK/ROCK signaling in a rat model of glaucoma. Pharmazie 69:889–893
Zhao Y, Wang J, Ballevre O, Luo H, Zhang W (2012) Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens Res 35:370–374
Acknowledgments
The authors gratefully acknowledge associate professor Sheng Liang for important discussions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Ye, HY., Li, ZY., Zheng, Y. et al. The attenuation of chlorogenic acid on oxidative stress for renal injury in streptozotocin-induced diabetic nephropathy rats. Arch. Pharm. Res. 39, 989–997 (2016). https://doi.org/10.1007/s12272-016-0771-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-016-0771-3