• Nirlep Chhiber Department of Biochemistry, Panjab University, Chandigarh 160015, India
  • Tanzeer Kaur Department of Biophysics, Panjab University, Chandigarh 160015, India
  • Surinder Singla Department of Biochemistry, Panjab University, Chandigarh 160015, India


Objective: To investigate the in vitro oxidant scavenging properties of rottlerin and to study the potential role of rottlerin on ethylene glycol induced nephrocalcinosis in rats.

Methods: In vitro oxidant scavenging properties of rottlerin were studied along with its effect on in vitro calcium phosphate mineralization. For the in vivo studies, hyperoxaluria was induced by administering 0.4 % ethylene glycol and 1 % ammonium chloride in drinking water to male wistar rats for 9 d. Rottlerin was administered intraperitoneally at 1mg/kg/d along with the hyperoxaluric agent. Total thiols content, activities of glutathione-S-transferase (GST), glutathione reductase (GR), Citrate synthase (CS), isocitrate dehydrogenase (ICDH), ATPase and urinary parameters were studied.

Results: Rottlerin showed in vitro DPPH, superoxide, and ABTS radical scavenging activity along with inhibition of calcium phosphate mineralization in an in vitro homogeneous system. The diminished activities of GST, GR, ICDH, CS, ATPase and level of total thiols were considerably stabilized by rottlerin, suggesting that rottlerin provides protection against oxalate induced oxidative damage.

Conclusion: We suggest that rottlerin protects the integrity of the renal cell by stabilizing the free-radical mediated damage. Thus, the present study reveals that the antioxidant nature of rottlerin protects the renal cells against oxalate-induced injury and thus, rottlerin may prevent against hyperoxaluria induced oxidative damage.

Keywords: Rottlerin, Hyperoxaluria, Oxidative stress, Antioxidant


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Khan SR, Byer KJ, Thamilselvan S. Crystal-cell interaction and apoptosis in the oxalate-associated injury of renal epithelial cells. J Am Soc Nephrol 1999;10:457–63.

Tiselius HG. Epidemiology and medical management of stone disease. BJU Int 2003;91:758–67.

Khand FD, Gordge MP, Robertson WG, Noronha-Dutra AA, Hothersall JS. Mitochondrial superoxide production during oxalate mediated oxidative stress in renal epithelial cells. Free Radical Biol Med 2002;32:1339-50.

Maioli E, Torricelli E, Valacchi G. Rottlerin and curcumin: a comparative analysis. Ann N Y Acad Sci 2012;1259:65–76.

Soltoff SP. Rottlerin: an inappropriate and ineffective inhibitor of PKCδ. Trends Pharmacol Sci 2007;28:453–8.

Maioli E, Greci L, Soucek K, Hyzdalova M, Pecorelli A, Fortino V, et al. Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells. J Biomed Biotechnol 2009. Doi:10.1155/2009/742936. [Epub 03 Feb 2010]

Longpre JM, Loo G. Protection of human colon epithelial cells against deoxycholate by rottlerin. Apoptosis 2008;13:1162–71.

Selvam R, Adhirai M. Vitamin E pretreatment prevents CsA induced crystal deposition in hyperoxaluric rats. Nephron 1997;75:77–81.

Muthukumar A, Selvam R. Role of glutathione on renal mitochondrial status in hyperoxaluria. Mol Cell Biochem 1998;185:77–84.

Sandhya P, Mohandass S, Varalakshmi P. Role of DL-α lipoic acid in gentamicin-induced nephrotoxicity. Mol Cell Biochem 1995;145:11–7.

Shen Q, Zhang B, Xu R, Wang Y, Ding X, Li P. Antioxidant activity in vitro of selenium contained protein from these-enriched. Bifidobacterium animals 01. Anaerobe 2010;16:380-6.

Kunchandy E, Rao MN. Oxygen radical scavenging activity of curcumin. Int J Pharmacogn 1990;58:237–40.

Huang MH, Huang SS, Wang BS, Sheu MJ, Hou WC. Antioxidant and anti-inflammatory properties of Cardiospermum halicacabum and its reference compounds ex vivo and in vivo. J. Ethnopharmacol 2011;133:743-50.

Kabra SG, Kabra V, Banerji P, Jain LK, Bhargava A, Chaturvedi RP. In vitro calculogenesis: Methods to develop concretions of desired chemical composition. Indian J Exp Biol 1978;16:212–7.

Singla S, Jethi RK. A simple method for the study of in vitro calculogenesis. Indian J Exp Biol 1981;19:283–5.

Trinder P. Colorimetric micro determination of calcium in serum. Analyst 1960;85:889–94.

Fiske CH, Subarrow Y. The colorimetric determination of phosphorus. Biol Chem 1925;66:375–400.

Kaur T, Bijarnia RK, Singla SK. In vivo efficacy of Trachyspermum ammi anti calcifying protein in a urolithiatic rat model. J Ethnopharmacol 2009;126:459–62.

Sedlak J. Changes of glutathione and protein-bound SH groups concentration in rat adrenals under acute and repeated stress. Endocrinol Exp 1982;16:103–9.

Bergmeyer H, Bernt E. Isocitrate dehydrogenase. Methods of enzymatic analysis. Verlag Chemie Weinheim/Bergstr; 1974. p. 479–80.

Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol 1985;113:484–90.

Habig WH, Pabst UJ, Jacob WB. Glutathione-S-transferase. J Biol Chem 1973;249:7130–9.

Griffiths DE, RL Houghton. Studies on energy-linked reactions: modified mitochondrial ATPase of oligomycin-resistant mutants of Saccharomyces cerevisiae. Eur J Biochem 1974;46:157-67.

Spinazzi M, Casarin A, Pertegato V, Saviati L, Angelini C. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc 2012;7:1235-46.

Churchill DN. Medical treatment to prevent recurrent calcium urolithiasis: a guide to critical appraisal. Miner Electrolyte Metab 1987;13:294–304.

Preminger GM. Renal-calculi: pathogenesis, diagnosis, and medical therapy. Semin Nephrol 1992;12:200–16.

Mattle D, Hess B. Preventive treatment of nephrolithiasis with alkali citrate: a critical review. Urol Res 2005;33:73–9.

Knoll T. Stone disease. Eur Urol Suppl 2007;6:717–22.

Pak CY. Etiology and treatment of urolithiasis. Am J Kidney Dis 1991;18:624–37.

Chhiber N, Sharma M, Kaur T, Singla SK. Mineralization in health and mechanism of kidney stone formation. Int J Pharm Sci Invent 2014;3:25-31.

Miller C, Kennington L, Cooney R. Oxalate toxicity in renal epithelial cells: characteristics of apoptosis and necrosis. Toxicol Appl Pharmacol 2000;162:132–41.

Thamilselvan S, Khan SR. Oxalate, and calcium oxalate crystals are injurious to renal epithelial cells: results of in vivo and in-vitro studies. J Nephrol 1998;11:66–9.

Nijveldt RJ, van Nood E, van Hoorn DE. Flavonoids: a review of the probable mechanism of action and potential applications. Am J Clin Nutr 2001;74:418–25.

Jeong BC, Kim BS, Kim JI, Kim HH. Effects of green tea on urinary stone formation: an in vivo and in vitro study. J Endourol 2006;20:356–61.

Park HK, Jeong BC, Sung MK, Park MY. Reduction of oxidative stress in cultured renal tubular cells and preventive effects on renal stone formation by the bioflavonoid quercetin. J Urol 2008;179:1620–6.

Khan SR. Hyperoxaluria-induced oxidative stress and antioxidants for renal protection. Urol Res 2005;33:349–57.

Akanae W, Tsujihata M, Yoshioka I, Nonomura N, Okuyama A. Orthosiphon grand forum has a protective effect in a calcium oxalate stone forming rat model. Urol Res 2010;38:89-96.

Randall A. The origin and growth of renal calculi. Ann Surg 1937;105:1009-27.

Chow K, Dixon J, Gilpin S, Kavanagh JP, Rao PN. Citrate inhibits the growth of residual fragments in an in vitro model of calcium oxalate renal stones. Kidney Int 2004;65:1724–30.

Roger K, Low MD, Stoller ML. Uric acid nephrolithiasis. Urol Clin North Am 1997;24:135.

Veena CK, Josephine A, Preetha SP, Rajesh NG, Varalakshmi P. Mitochondrial dysfunction in an animal model of hyperoxaluria: a prophylactic approach with fucoidan. Eur J Pharmacol 2008;579:330–6.



How to Cite

Chhiber, N., T. Kaur, and S. Singla. “SALUBRIOUS EFFECT OF ROTTLERIN ON HYPEROXALURIA INDUCED OXIDATIVE DAMAGE IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 13, Mar. 2016, pp. 13-18,