Main Article Content
Abstract
Aim: To assess the effects of L-carnitine in protection from cisplatin–induced nephrotoxicity in cancer patients.
Patients and methods:28 patients were participated in the study and successfully completed their treatment cycles. They were randomized into two groups (N=14 in each). In group I, patients received six cycles of cisplatin based regimen with 21 days-intervals. In group II, patients received L-carnitine(500 mg oral tablet twice daily) plus cisplatin based regimen. GFR (Modification of Diet in renal Diseases formula) was measured at base line and 21 days after 1, 2, 4 and 6 cycles but IL-18 was measured at base line and 1 day after 1, 2, 4 and 6 cycles of cisplatin based regimen.
Results:In patients of group I, cisplatin-based regimen caused significant (P<0.05) increment in serum creatinine and urea levels, highly significant (P<0.01) increment in serum urinary IL-18 levels, and significant (P<0.05) decrement in GFR in comparison to base line levels.
Conclusions:Each of L-carnitine significantly ameliorated nephrotoxicity in patients that received cisplatin.
Keywords
Article Details
References
- Lebwohl D, Canetta R. (1998): Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 34:1522–34.
- Pabla N, Dong Z. (2008): Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 73, 994–1007.
- Goldstein RS, Mayor GH. (1983): Minireview. The nephrotoxicity of cisplatin. Life Sci. 32, 685–690.
- Yao X, Panichpisal K, Kurtzman N, et al. (2007): Cisplatin nephrotoxicity: a review, Am. J. Med. Sci., 334, 115-124.
- Miller RP, Tadagavadi RK, Ramesh G, et al. (2010): Mechanisms of cisplatin nephrotoxicity. Toxins 2, 2490–2518.
- Tein I, Bukovac SW, Xie ZW. (1996): Characterization of the human plasmalemmalcarnitine transporter in cultured skin fibroblasts. Arch. Biochem. Biophys. 329, 145–155.
- Engel AG, Rebouche CJ. (1984): Carnitine metabolism and inborn errors. J. Inher. Metabol. Dis. 7, 38–43.
- Steiber A, Kerner J, Hoppel CL. (2004): Carnitine: a nutritional, biosynthetic, and functional perspective. Mol. Aspects Med. 25, 455– 473.
- Stewart DJ, Morgan Jr LR, Verma S, et al. (1995): Pharmacology, relative bioavailability, and toxicity of three different oral cyclophosphamide preparations in a randomized, cross-over study. Invest. New Drugs 13, 99–107.
- Malaguarnera M, Risino C, Gargante MP, et al. (2006): Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia. World J. Gastroenterol. 12, 4541–4545.
- Heuberger W, Berardi S, Jacky E, et al. (1998): Increased urinary excretion of carnitine in patients treated with cisplatin. Eur. J. Clin. Pharmacol. 54, 503–508.
- Arafa HM, (2008): Carnitine deficiency aggravates carboplatin nephropathy through deterioration of energy status, oxidant/antioxidant balance, and inflammatory endocoids. Toxicology 254, 51– 60.
- Sayed-Ahmed MM, Khattab M, Khalifa A, et al. (1999): And Osman, A.M: Potenial promise of using L-carnitine and Coenzyme Q10 as protective agents against cisplatin-induced nephrotoxicity. J. Egypt. Natl. Cancer Inst. 11, 167–173.
- Chang B, Nishikawa M, Sato E, et al. (2002): L-carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch. Biochem. Biophys. 405, 55–64.
- Yürekli Y, Ünak P, Yenisey C, et al. (2011): L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake Mol Imaging RadionuclTher. 20(1): 1–6.
- Levey AS, Eckardt KU, Tsukamoto Y, et al. (2005): Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67: 2089–2100.
- Levey AS, Coresh J, Greene T, et al. (2007): Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration Standardized serum creatinine rate with values. ClinChem 53, 766-772.
- Larsson A, Malm J, Grubb A, et al. (2004): Calculation of glomerular filtration rate overexpressed in mL / min from plasma cystatin C values in mg / L. Scand J Clin Lab Invest 64, 25-30.
- Okamura H, Tsutsi H, Komatsu T, et al. (1995): Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 378 : 88 –91.
- Nakanishi K, Yoshimoto T, Tsutsui H, et al. (2001): Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 12 : 53 –72 .
- Neighbors M, Xu X, Barrat FJ, et al. (2001): A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on interferon gamma production. J Exp Med 194: 343 –354.
- Mehta RL. (2006): Urine IL-18 levels as a predictor of acute kidney injury in intensive care patients. Nat ClinPractNephrol 2:252-253.
- Parikh CR, Jani A, Melnikov VY, et al. (2004): Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405-414.
- Bodnara L, Wcisloa G, Gasowska-Bodnarb A, et al. (2008): protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: A randomised phase II study. Europ J Canc 44, 2608–2614.
- Ramesh G, Reeves WB. (2002): TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest. 110:835–42.
- Wu H, Craft ML, Wang P, et al. (2008): IL-18 contributes to renal damage after ischemia-reperfusion. J Am Soc Nephrol.19:2331 _4.
- Parikh CR, Abraham E, Ancukiewicz M, et al. (2005): Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the ICU. J Am SocNephrol 16:3046-3052.
- Mister M, Noris M, Szymczuk J, et al. (2002): Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion. Kidn Intern. 61, 1064–1078
- Chapela SP, Kriguer N, Fernandez E.H, et al. (2009): Involvement of L-Carnitine in Cellular Metabolism: Beyond Acyl-CoA Transport. Mini-Reviews in Medicinal Chemistry. 9:1518–1526.
- Tufekci O, Gunes D, Ozog˘ ul C, et al. (2009): Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity. Chemoth 55, 451–459.
References
Lebwohl D, Canetta R. (1998): Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 34:1522–34.
Pabla N, Dong Z. (2008): Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 73, 994–1007.
Goldstein RS, Mayor GH. (1983): Minireview. The nephrotoxicity of cisplatin. Life Sci. 32, 685–690.
Yao X, Panichpisal K, Kurtzman N, et al. (2007): Cisplatin nephrotoxicity: a review, Am. J. Med. Sci., 334, 115-124.
Miller RP, Tadagavadi RK, Ramesh G, et al. (2010): Mechanisms of cisplatin nephrotoxicity. Toxins 2, 2490–2518.
Tein I, Bukovac SW, Xie ZW. (1996): Characterization of the human plasmalemmalcarnitine transporter in cultured skin fibroblasts. Arch. Biochem. Biophys. 329, 145–155.
Engel AG, Rebouche CJ. (1984): Carnitine metabolism and inborn errors. J. Inher. Metabol. Dis. 7, 38–43.
Steiber A, Kerner J, Hoppel CL. (2004): Carnitine: a nutritional, biosynthetic, and functional perspective. Mol. Aspects Med. 25, 455– 473.
Stewart DJ, Morgan Jr LR, Verma S, et al. (1995): Pharmacology, relative bioavailability, and toxicity of three different oral cyclophosphamide preparations in a randomized, cross-over study. Invest. New Drugs 13, 99–107.
Malaguarnera M, Risino C, Gargante MP, et al. (2006): Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia. World J. Gastroenterol. 12, 4541–4545.
Heuberger W, Berardi S, Jacky E, et al. (1998): Increased urinary excretion of carnitine in patients treated with cisplatin. Eur. J. Clin. Pharmacol. 54, 503–508.
Arafa HM, (2008): Carnitine deficiency aggravates carboplatin nephropathy through deterioration of energy status, oxidant/antioxidant balance, and inflammatory endocoids. Toxicology 254, 51– 60.
Sayed-Ahmed MM, Khattab M, Khalifa A, et al. (1999): And Osman, A.M: Potenial promise of using L-carnitine and Coenzyme Q10 as protective agents against cisplatin-induced nephrotoxicity. J. Egypt. Natl. Cancer Inst. 11, 167–173.
Chang B, Nishikawa M, Sato E, et al. (2002): L-carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch. Biochem. Biophys. 405, 55–64.
Yürekli Y, Ünak P, Yenisey C, et al. (2011): L-Carnitine Protection Against Cisplatin Nephrotoxicity In Rats: Comparison with Amifostin Using Quantitative Renal Tc 99m DMSA Uptake Mol Imaging RadionuclTher. 20(1): 1–6.
Levey AS, Eckardt KU, Tsukamoto Y, et al. (2005): Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 67: 2089–2100.
Levey AS, Coresh J, Greene T, et al. (2007): Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration Standardized serum creatinine rate with values. ClinChem 53, 766-772.
Larsson A, Malm J, Grubb A, et al. (2004): Calculation of glomerular filtration rate overexpressed in mL / min from plasma cystatin C values in mg / L. Scand J Clin Lab Invest 64, 25-30.
Okamura H, Tsutsi H, Komatsu T, et al. (1995): Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 378 : 88 –91.
Nakanishi K, Yoshimoto T, Tsutsui H, et al. (2001): Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 12 : 53 –72 .
Neighbors M, Xu X, Barrat FJ, et al. (2001): A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on interferon gamma production. J Exp Med 194: 343 –354.
Mehta RL. (2006): Urine IL-18 levels as a predictor of acute kidney injury in intensive care patients. Nat ClinPractNephrol 2:252-253.
Parikh CR, Jani A, Melnikov VY, et al. (2004): Urinary interleukin-18 is a marker of human acute tubular necrosis. Am J Kidney Dis 43:405-414.
Bodnara L, Wcisloa G, Gasowska-Bodnarb A, et al. (2008): protection with magnesium subcarbonate and magnesium sulphate in patients with epithelial ovarian cancer after cisplatin and paclitaxel chemotherapy: A randomised phase II study. Europ J Canc 44, 2608–2614.
Ramesh G, Reeves WB. (2002): TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest. 110:835–42.
Wu H, Craft ML, Wang P, et al. (2008): IL-18 contributes to renal damage after ischemia-reperfusion. J Am Soc Nephrol.19:2331 _4.
Parikh CR, Abraham E, Ancukiewicz M, et al. (2005): Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the ICU. J Am SocNephrol 16:3046-3052.
Mister M, Noris M, Szymczuk J, et al. (2002): Propionyl-L-carnitine prevents renal function deterioration due to ischemia/reperfusion. Kidn Intern. 61, 1064–1078
Chapela SP, Kriguer N, Fernandez E.H, et al. (2009): Involvement of L-Carnitine in Cellular Metabolism: Beyond Acyl-CoA Transport. Mini-Reviews in Medicinal Chemistry. 9:1518–1526.
Tufekci O, Gunes D, Ozog˘ ul C, et al. (2009): Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity. Chemoth 55, 451–459.
