Abstract
Cyclosporine A (CsA) has been universally used as an immunosuppressant for the management of organ transplantation and various autoimmune diseases. However, nephrotoxicity due to CsA remains to be an important clinical challenge. In the present investigation, an attempt has been made to appraise the effect of sulphated polysaccharides on oxidative renal injury caused by CsA. Adult male Wistar rats were divided into four groups. Two groups received CsA by oral gavage (25 mg/kg body weight) for 21 days to provoke nephrotoxicity, one of which simultaneously received sulphated polysaccharides subcutaneously, (5 mg/kg body weight). A vehicle (olive oil) treated control group and sulphated polysaccharides drug control were also built-in. An increase in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamin C and vitamin E) are the salient features observed in CsA induced nephrotoxicity. CsA induced impairment of renal toxicity was evident from the marked decline in the activities of renal marker enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase, as well as an apparent increase in the serum urea, uric acid and creatinine; diagnostic of renal damage was normalized by sulphated polysaccharides co-administration. Sulphated polysaccharides treatment showed an effectual role in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. These observations emphasize the antioxidant property of sulphated polysaccharides and its cytoprotective action against CsA induced nephrotoxicity.
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References
Kahan BD: Cyclosporine. N Engl J Med 321: 1725–1738, 1989
Morris PJ: Cyclosporin. In: Kidney transplantation Morris PJ. (ed.), 1994, pp 179–201
Mason J: The pathophysiology of Sandimmune (cyclosporine) in man and animals. Pediatr Nephrol 4: 554–574, 1990
Humes HD, Jackson NM, O'Connor RP, Hunt DA, White MD: Pathogenetic mechanisms of nephrotoxicity: insights into cyclosporine nephrotoxicity. Transplant Proc 17: 51–62, 1985
Walker RJ, Lazzaro VA, Duggin GG, Horvath JS, Tiller DJ: Synergistic toxicity of cyclosporin A and streptomycin in renal epithelial cell cultures. Res Commun Chem Pathol Pharmacol 62: 447–460, 1988
Baud L, Ardaillou R: Involvement of reactive oxygen species in kidney damage. Br Med Bull 49: 621–629, 1993
Serino F, Grevel J, Napoli KL, Kahan BD, Strobel HW: Oxygen radical formation by the cytochrome P450 system as a cellular mechanism for cyclosporine toxicity. Transplant Proc 26: 2916–2917, 1994
Suleymanlar G, Suleymanlar I, Shapiro JI, Chan L: Possible role of lipid peroxidation in cyclosporine nephrotoxicity in rats. Transplant Proc 26: 2888–2889, 1994
Teas J: The consumption of seaweed as a protective factor in the etiology of breast cancer. Med Hypotheses 7: 601–613, 1981
Lahaye M, Kaffer B: Seaweed dietary fibers structure physiochemical and biological properties relevant to intestinal physiology. Sci Aliments 17: 563–564, 1997
Matsukawa R, Dubinsky Z, Kishimoto E, Masakki K, Masuda Y, Takeuchi T: A comparison of screening methods for antioxidant activity in seaweeds. J Appl Phycol 9: 29–35, 1997
Ramarathnam N, Osawa T, Ochi H, Kawakishi S: The contribution of plant food antioxidants to human health. Trends Food Sci Technol 6:75–82, 1995
Marco AM, Guimaraes, Paulo AS, Mourao: Urinary excretion of sulfated polysaccharides administered to wistar rats suggests a renal permselectivity to these polymers based on molecular size. Biochim Biophys Acta 1335: 161–172, 1997
Jimenez-Escrig A, Jimenez-Jimenez I, Pulido R, Saura-Calixto F: Antioxidant activity of fresh and processed edible seaweeds. J Sci Food Agric 81: 530–534, 2001
Matsukawa R: A comparison of screening methods for antioxidant activity in seaweeds. J Appl Phycol 9: 29–35, 1997
Yan X, Nagata T, Fan X: Antioxidative activities in some common seaweeds. Plant Foods Hum Nutr 52: 253–262, 1998
Vieira RP, Mulloy B, Mourao PA: Structure of a fucose-branched chondroitin sulfate from sea cucumber. Evidence for the presence of 3-O-sulfo-beta-D-glucoronosyl residues. J Biol Chem 266: 13530–13536, 1991
King J: The hydrolases-acid and alkaline phosphatases, in: Van (Ed.), Practical Clinical Enzymology, Nostrand company Limited, London, 1965, pp. 191–208
King J: The dehydrogenases or oxidoreductases-lactate dehydrogenase, in: D. Van (Ed.), Practical Clinical Enzymology, Nostrand Company Limited, London, 1965, pp. 83–93
Natelson S, Scott ML, Beffa C: A rapid method for the estimation of urea in biological fluids by means of the reaction between diacetyl monoxime and urea. Am J Clin Pathol 21: 275–281, 1951
Caraway WT: Uric acid. In: Standard Methods of clinical chemistry, Seligson D. (Ed.), Academic Press, New York: 1963, 239–247
Owen JA, Iggo TB, Scandrett FJ, Stemart IP: Determination of creatinine in plasma or serum and in urine, a critical examination. Biochem J 58: 426–437, 1954
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275, 1951
Hogberg J, Larson RE, Kristoferson A, Orrenius S: NADPH-dependent reductase solubilised from microsomes by peroxidation and its activity. Biochem Biophy Res Common. 56: 836–842, 1974
Devasagayam TP: Lipid peroxidation in rat uterus. Biochim Biophys Acta 876: 507–514, 1986
Marklund S, Marklund G: Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469–474, 1974
Sinha AK: Colorimetric assay of catalase. Anal Biochem 47: 389–394, 1972
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG: Selenium: biochemical role as a component of glutathione peroxidase. Science 179: 588–590, 1973
Staal GE, Visser J, Veeger C: Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 185: 39–48, 1969
Habig WH, Pabst MJ, Jakoby WB: Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130–7139, 1974
Balansky D, Bernstein RE: The purification and properties of glucose-6-phosphate dehydrogenase from human erythrocytes. Biochim Biophys Acta 67: 313–315, 1963
Moron MS, Depierre JW, Mannervik B: Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582: 67–78, 1979
Omaye ST, Turnbull JD, Sauberlich HE: Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62: 3–11, 1979
Desai ID: Vitamin E analysis methods for animal tissues. Methods Enzymol 105: 138–147, 1984
Campistol JM, Sacks SH: Mechanisms of nephrotoxicity. Transplantation 69: SS5-SS10, 2000
Strzelecki T, Kumar S, Khauli R, Menon M: Impairment by cyclosporine of membrane-mediated functions in kidney mitochondria. Kidney Int 34: 234–240, 1988
Inselmann G, Baumann K: Effect of cyclosporine A on accumulation of tetraethylammonium and p-aminohippurate and or lipid peroxidation in rat renal microsomes and cortical slices. Renal failure 12: 165–169, 1990
Shi SH, Zheng SS, Jia CK, Zhu YF, Xie HY: Inhibitory effect of tea polyphenols on transforming growth factor-beta1 expression in rat with cyclosporine A-induced chronic nephrotoxicity. Acta Pharmacol Sin 25: 98–103, 2004
Durak I, Karabacak HI, Buyukkocak S, Cimen MY, Kacmaz M, Omeroglu E, Ozturk HS: Impaired antioxidant defense system in the kidney tissues from rabbits treated with cyclosporine. Protective effects of vitamins E and C. Nephron 78: 207–211, 1998
Parra T, de Arriba G, Conejo JR, Cantero M, Arribas I, Rodriguez-Puyol D, Rodriguez-Puyol M, Carballo F: Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats: effect of vitamin E on cyclosporine nephrotoxicity. Transplantation 66: 1325–1329, 1998
Guder WG, Ross RD: Enzyme distribution along the nephron. Kidney Int 26: 101–111, 1984
Maruhn D, Paar D, Bomhard E: Diagnostic sensitivity or urinary enzymes in experimental kidney damage in the rat. In: Biologic prospective: comptes rendus da 5 e collogue' International do pont-a-mousson, Galteau, M.M., Siest, G. and Henny, J. (Eds). Masson, Paris, 1983, pp 943–945
Raghavendran HR, Sathivel A, Devagi T: Hepatoprotective nature of seaweed alcoholic extract on acetaminophen induced hepatic oxidative stress. J Health Science 50: 42–46, 2004
Inselmann G, Hannemann J, Baumann K: Cyclosporine A induced lipid peroxidation and influence on glucose-6-phosphatase in rat hepatic and renal microsomes. Res Commun Chem Pathol Pharmacol 68: 189–203, 1990
Mohamadin AM, El-Beshbishy HA, El-Mahdy MA: Green tea extract attenuates cyclosporine A-induced oxidative stress in rats. Pharmacol Res 51: 51–57, 2005
Tariq M, Morais C, Sobki S, Al sulaiman M, Al khader A: N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol Dial Transplant 14: 923–929, 1999
Raghavendran HR, Sathivel A, Devagi T: Protective effect of Sargassum polycystum (Brown alga) against acetaminophen-induced lipid peroxidation in rats. Phytother Res 19: 113–115, 2005
Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary MD, Remacle J: Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 51: 283–297, 1990
Pang ZJ, Chen Y, Zhou M, Wan J. Effect of polysaccharide krestin on glutathione peroxidase gene expression in mouse peritoneal macrophages. Br J Biomed Sci 57: 130–136, 2000
Pang ZJ, Chen Y, Zhou M. Polysaccharide krestin enhances manganese superoxide dismutase activity and mRNA expression in mouse peritoneal macrophages. Am J Chin Med 28: 331–341, 2000
Bray TM, Taylor CG. Tissue glutathione, nutrition, and oxidative stress. Can J Physiol Phamacol 71: 746–751, 1993
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Josephine, A., Veena, C.K., Amudha, G. et al. Evaluating the Effect of Sulphated Polysaccharides on Cyclosporine A Induced Oxidative Renal Injury. Mol Cell Biochem 287, 101–108 (2006). https://doi.org/10.1007/s11010-005-9081-7
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DOI: https://doi.org/10.1007/s11010-005-9081-7