THE ROLE OF NATURAL ANTIOXIDANTS AS POTENTIAL THERAPEUTIC AGENT IN NEPHROLITHIASIS

Authors

  • AGGARWAL DEEPIKA Department of Biochemistry, Panjab University Chandigarh, India
  • SHARMA MINU
  • SINGLA SURINDER K

Abstract

Renal injury and inflammation caused by ROS play a major role in stone formation. Under the hyperoxaluric condition, crystal deposition results in angiotensin II (Ang II) activation. NADPH Oxidase is stimulated by activated Ang II, leading to ROS production, which can damage renal cells. Oxidative stress also results in mitochondrial dysfunction and release of pro-apoptotic factors from depolarized mitochondria that result in apoptosis that leads to renal injury. Crystal retention in the kidney requires tubular epithelial injury accompanied by luminal expression of HA, OPN, and CD44. The expression of these molecules turns a non–crystal-binding epithelium into a crystal-binding one, thereby setting the stage for crystal retention. Recently many antioxidants have been studied that prevent hyperoxaluria mediated nephrolithiasis. Antioxidant treatment significantly reduces CaOx crystal deposition in kidneys. Naturally occurring antioxidants such as Vitamin E, Apocynin, Phycocyanin, Fucoidin, Gallotannins, Rottlerin, Lupeol, Curcumin, etc. have shown significant effect in combating renal injury which is an early event in nephrolithiasis. These findings point towards a great potential for the therapeutic application of antioxidants and free radical scavengers to reduce stone occurrence particularly under hyperoxaluric conditions. This review article attempts to compile various naturally occurring antioxidants used in treatment of nephrolithiasis.

Keywords: Calcium oxalate, Oxidative stress, Hyperoxaluria, Reactive oxygen species, antioxidants

References

Brener ZZ, Winchester JF, Salman H, Bergman M. Nephrolithiasis: evaluation and management. South Med J 2011; 104:133-9.

Hou J. The role of claudin in hypercalciuric nephrolithiasis. Curr Urol Rep 2013; 14:5-12.

Khandrika L, Koul S, Meacham RB, Koul HK. Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo. PLoS One 2012; 7:e44174.

Joshi S, Saylor BT, Wang W, Peck AB, Khan SR. Apocynin-treatment reverses hyperoxaluria induced changes in NADPH oxidase system expression in rat kidneys: a transcriptional study. PLoS One 2012; 7:e47738.

Li CY, Deng YL, Sun BH. Taurine protected kidney from oxidative injury through mitochondrial-linked pathway in a rat model of nephrolithiasis. Urol Res 2009; 37:211-20.

Zuo J, Khan A, Glenton PA, Khan SR. Effect of NADPH oxidase inhibition on the expression of kidney injury molecule and calcium oxalate crystal deposition in hydroxy-L-proline-induced hyperoxaluria in the male Sprague-Dawley rats. Nephrol Dial Transplant 2011; 26:1785-96.

Hovda KE, Guo C, Austin R, McMartin KE. Renal toxicity of ethylene glycol results from internalization of calcium oxalate crystals by proximal tubule cells. Toxicol Lett 2010; 192:365-72.

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

Tsujihata M, Tsujikawa K, Tei N, Yoshimura K, Okuyama A. Urinary macromolecules and renal tubular cell protection from oxalate injury: comparison of normal subjects and recurrent stone formers. Int J Urol 2006; 13:197-201.

Huang HS, Ma MC, Chen CF, Chen J. Lipid peroxidation and its correlations with urinary levels of oxalate, citric acid, and osteopontin in patients with renal calcium oxalate stones. Urology 2003; 62:1123-8.

Khan SR. Role of renal epithelial cells in the initiation of calcium oxalate stones. Nephron Exp Nephrol 2004; 98:e55-60.

Thamilselvan S, Byer KJ, Hackett RL, Khan SR. Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 2000; 164:224-9.

Thamilselvan S, Hackett RL, Khan SR. Lipid peroxidation in ethylene glycol induced hyperoxaluria and calcium oxalate nephrolithiasis. J Urol 1997; 157:1059-63.

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

Cao LC, Honeyman TW, Cooney R, Kennington L, Scheid CR, Jonassen JA. Mitochondrial dysfunction is a primary event in renal cell oxalate toxicity. Kidney Int 2004; 66:1890-900.

Jonassen JA, Cao LC, Honeyman T, Scheid CR. Intracellular events in the initiation of calcium oxalate stones. Nephron Exp Nephrol 2004; 98:e61-4.

Jonassen JA, Cao LC, Honeyman T, Scheid CR. Mechanisms mediating oxalate-induced alterations in renal cell functions. Crit Rev Eukaryot Gene Expr 2003; 13:55-72.

Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, Egido J. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl 2002:S12-22.

Umekawa T, Byer K, Uemura H, Khan SR. Diphenyleneiodium (DPI) reduces oxalate ion- and calcium oxalate monohydrate and brushite crystal-induced upregulation of MCP-1 in NRK 52E cells. Nephrol Dial Transplant 2005; 20:870-8.

Umekawa T, Hatanaka Y, Kurita T, Khan SR. Effect of angiotensin II receptor blockage on osteopontin expression and calcium oxalate crystal deposition in rat kidneys. J Am Soc Nephrol 2004; 15:635-44.

Hanna IR, Taniyama Y, Szocs K, Rocic P, Griendling KK. NAD(P)H oxidase-derived reactive oxygen species as mediators of angiotensin II signaling. Antioxid Redox Signal 2002; 4:899-914.

Vidya L, Varalakshmi P. Control of urinary risk factors of stones by betulin and lupeol in experimental hyperoxaluria. Fitoterapia 2000; 71:535-43.

Verkoelen CF, Van Der Boom BG, Romijn JC. Identification of hyaluronan as a crystal-binding molecule at the surface of migrating and proliferating MDCK cells. Kidney Int 2000; 58:1045-54.

Verhulst A, Asselman M, Persy VP, Schepers MS, Helbert MF, Verkoelen CF, De Broe ME. Crystal retention capacity of cells in the human nephron: involvement of CD44 and its ligands hyaluronic acid and osteopontin in the transition of a crystal binding- into a nonadherent epithelium. J Am Soc Nephrol 2003; 14:107-15.

Huang HS, Chen J, Chen CF, Ma MC. Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors. Kidney Int 2006; 70:699-710.

Farooq SM, Asokan D, Kalaiselvi P, Sakthivel R, Varalakshmi P. Prophylactic role of phycocyanin: a study of oxalate mediated renal cell injury. Chem Biol Interact 2004; 149:1-7.

Sudhahar V, Veena CK, Varalakshmi P. Antiurolithic effect of lupeol and lupeol linoleate in experimental hyperoxaluria. J Nat Prod 2008; 71:1509-12.

Lee HJ, Jeong SJ, Lee EO, Bae H, Lieske JC, Kim SH. 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose reduces renal crystallization and oxidative stress in a hyperoxaluric rat model. Kidney Int 2011; 79:538-45.

Lee HJ, Jeong SJ, Park MN, Linnes M, Han HJ, Kim JH, Lieske JC, Kim SH. Gallotannin suppresses calcium oxalate crystal binding and oxalate-induced oxidative stress in renal epithelial cells. Biol Pharm Bull 2012; 35:539-44.

Bashir S, Gilani AH. Antiurolithic effect of berberine is mediated through multiple pathways. Eur J Pharmacol 2011; 651:168-75.

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

Antunes LM, Darin JD, Bianchi Nde L. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res 2001; 43:145-50.

Hadjzadeh MA, Mohammadian N, Rahmani Z, Rassouli FB. Effect of thymoquinone on ethylene glycol-induced kidney calculi in rats. Urol J 2008; 5:149-55.

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.

Tsujihata M, Yoshioka I, Tsujimura A, Nonomura N, Okuyama A. Why does atorvastatin inhibit renal crystal retention? Urol Res 2011; 39:379-83.

Li CY, Deng YL, Sun BH. Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis. Int Urol Nephrol 2009; 41:823-33.

Bijarnia RK, Kaur T, Aggarwal K, Singla SK, Tandon C. Modulatory effects of N-acetylcysteine on hyperoxaluric manifestations in rat kidney. Food Chem Toxicol 2008; 46:2274-8.

Jenkins JK, Huang H, Ndebele K, Salahudeen AK. Vitamin E inhibits renal mRNA expression of COX II, HO I, TGFbeta, and osteopontin in the rat model of cyclosporine nephrotoxicity. Transplantation 2001; 71:331-4.

Neuzil J, Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 1994; 269:16712-9.

Farooq SM, Asokan D, Sakthivel R, Kalaiselvi P, Varalakshmi P. Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury. Clin Chim Acta 2004; 348:199-205.

Farooq SM, Ebrahim AS, Subramhanya KH, Sakthivel R, Rajesh NG, Varalakshmi P. Oxalate mediated nephronal impairment and its inhibition by c-phycocyanin: a study on urolithic rats. Mol Cell Biochem 2006; 284:95-101.

Sowers MR, Jannausch M, Wood C, Pope SK, Lachance LL, Peterson B. Prevalence of renal stones in a population-based study with dietary calcium, oxalate, and medication exposures. Am J Epidemiol 1998; 147:914-20.

Chen H, Li H, Cao F, Zhen L, Bai J, Yuan S, Mei Y. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose protects PC12 Cells from MPP(+)-mediated cell death by inducing heme oxygenase-1 in an ERK- and Akt-dependent manner. J Huazhong Univ Sci Technolog Med Sci 2012; 32:737-45.

Duke JA. Handbook of medicinal herbs: CRC, 2002.

Bashir S, Gilani AH, Siddiqui AA, Pervez S, Khan SR, Sarfaraz NJ, Shah AJ. Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats. Phytother Res 2010; 24:1250-5.

Gschwendt M, Muller HJ, Kielbassa K, Zang R, Kittstein W, Rincke G, Marks F. Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun 1994; 199:93-8.

Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003; 26:87-98.

Mouhajir F, Pedersen JA, Rejdali M, Towers GHN. Antimicrobial thymohydroquinones of Moroccan Nigella sativa seeds detected by electron spin resonance. Pharmaceutical biology 1999; 37:391-5.

Wijesekara I, Pangestuti R, Kim S-K. Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydrate Polymers 2010; 84:14-21.

Veena CK, Josephine A, Preetha SP, Varalakshmi P. Beneficial role of sulfated polysaccharides from edible seaweed< i> Fucus vesiculosus in experimental hyperoxaluria. Food chemistry 2007; 100:1552-9.

Wassmann S, Laufs U, Muller K, Konkol C, Ahlbory K, Baumer AT, Linz W, Bohm M, Nickenig G. Cellular antioxidant effects of atorvastatin in vitro and in vivo. Arterioscler Thromb Vasc Biol 2002; 22:300-5.

Tsujihata M, Momohara C, Yoshioka I, Tsujimura A, Nonomura N, Okuyama A. Atorvastatin inhibits renal crystal retention in a rat stone forming model. J Urol 2008; 180:2212-7.

Keenan KP, Wallig MA, Haschek WM. Nature via Nurture Effect of Diet on Health, Obesity, and Safety Assessment. Toxicologic Pathology 2013.

Bouckenooghe T, Remacle C, Reusens B. Is taurine a functional nutrient? Curr Opin Clin Nutr Metab Care 2006; 9:728-33.

Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr 2006; 136:1636S-40S.

Bijarnia RK, Kaur T, Singla SK, Tandon C. A novel calcium oxalate crystal growth inhibitory protein from the seeds of Dolichos biflorus (L.). Protein J 2009; 28:161-8.

Kaur T, Bijarnia RK, Singla SK, Tandon C. In vivo efficacy of Trachyspermum ammi anticalcifying protein in urolithiatic rat model. J Ethnopharmacol 2009; 126:459-62.

Aggarwal A, Tandon S, Singla SK, Tandon C. Reduction of oxalate-induced renal tubular epithelial (NRK-52E) cell injury and inhibition of calcium oxalate crystallisation in vitro by aqueous extract of Achyranthes aspera. International Journal of Green Pharmacy 2010; 4:159.

Aggarwal A, Singla SK, Gandhi M, Tandon C. Preventive and curative effects of Achyranthes aspera Linn. extract in experimentally induced nephrolithiasis. Indian Journal of Experimental Biology 2012; 50:201.

Aggarwal A, Tandon S, Singla SK, Tandon C. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris. International braz j urol 2010; 36:480-9.

Kamboj P, Aggarwal M, Puri S, Singla SK. Effect of aqueous extract of Tribulus terrestris on oxalate-induced oxidative stress in rats. Indian journal of nephrology 2011; 21:154.

Published

2013-07-01

How to Cite

DEEPIKA, A., S. MINU, and S. SURINDER K. “THE ROLE OF NATURAL ANTIOXIDANTS AS POTENTIAL THERAPEUTIC AGENT IN NEPHROLITHIASIS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 6, no. 3, July 2013, pp. 48-53, https://innovareacademics.in/journals/index.php/ajpcr/article/view/205.

Issue

Section

Articles