• Logo
  • SBMUJournals

Renal Protective Effects of L-Carnitine on Lead-Induced Nephropathy in Wistar Rats

Marzie Hejazy, Davood Najafi
51

Views

PDF

Abstract

Background: Lead is a heavy metal used in industries in developing countries. Lead exposure remains a widespread problem. Lead may induce molecular damage in the kidney as a consequence of Reactive Oxygen Species (ROS) formation, induction of caspase-3, and apoptosis.
Methods: Thirty male Wistar rats (Mean±SD weight: 300±20 g) were randomly divided into 3 equal groups: control (normal saline, oral), lead group (lead 100 mg/kg/d, oral) and lead+L-Carnitine (lead 100 mg/kg+L-Carnitine 200 mg/kg, intraperitoneal injection) for one week. At the end of the experiment, plasma creatine kinase activity, plasma creatinine and urea concentrations and plasma Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), catalase and nitric oxide levels were determined. Glutathione and malondialdehyde levels in renal tissue were also measured.
Results: Creatine kinase, creatinine and urea levels increased significantly, in the group treated with lead (P<0.05), compared to the control group. Administration of L-Carnitine in (Lead+carnitine treated group) significantly (P<0.05) decreased creatine kinase activity and plasma urea and creatinine contents. Enzymatic activity (SOD, GPx, and CAT) decreased significantly in the lead group, in comparison with the control group (P<0.05). Treatment with L-Carnitine significantly retrieved the depletion in enzyme activity (P<0.05). However, there were no significant differences in the GPx parameter between the Lead+carnitine group, in comparison with the control group.
Conclusion: L-Carnitine administration in rats with lead-induced nephropathy led to improved kidney protection, due to the reduction of Lipid Peroxidation (LPO). Furthermore, L-Carnitine prevents the adverse effects of Reactive Oxygen Species (ROS), which is an important biomolecules mechanism.


Keywords

lipid peroxidation (LPO), l-carnitine, reactive oxygen species (ROS), nephropathy, lead

References

Liu CM, Sun YZ, Sun JM, Ma JQ, Cheng C. Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-kB pathway. Biochimica et Biophysica Acta- General Subjects. 2012; 1820(10):1693-703. [DOI:10.1016/j.bbagen.2012.06.011] [PMID]

Basgen JM, Sobin C. Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice. Toxicology Letters. 2014; 225(1):48-56. [DOI:10.1016/j.toxlet.2013.11.031] [PMID] [PMCID]

Mudipalli A. Lead hepatotoxicity & potential health effects. Indian Journal of Medical Research. 2007; 126(6):518-27. [PMID]

Pande M, Flora SJ. Lead induced oxidative damage and its response to combined administration of α-lipoic acid and succimers in rats. Toxicology. 2002; 177(2):187-96. [DOI:10.1016/S0300-483X(02)00223-8]

Abdel-Moneim AE, Dkhil MA, Al-Quraishy S. The potential role of flaxseed oil on lead acetateinduced kidney injure in adult male albino rats. African Journal of Biotechnology. 2011; 10(8):1436-41.

Fadrowski JJ, Navas-Acien A, Tellez-Plaza M, Guallar E, Weaver VM, Furth SL. Blood lead level and kidney function in US adolescents: The third national health and nutrition examination survey. Archives of Internal Medicine. 2010; 170(1):75-82. [DOI:10.1001/archinternmed.2009.417] [PMID] [PMCID]

Buyuklu M, Kandemir FM, Ozkaraca M, Set T, Bakirci EM, Topal E. Protective effect of curcumin against contrast induced nephropathy in rat kidney: What is happening to oxidative stress, inflammation, autophagy and apoptosis. European Review for Medical and Pharmacological Sciences. 2014; 18(4):461-70. [PMID]

Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. New England Journal of Medicine. 2003; 348(2):101-8. [DOI:10.1056/NEJMoa020549] [PMID]

Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, et al. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: Possible role in lead-induced nephrotoxicity. Environmental Health Perspectives. 2015; 123(2):120-7. [DOI:10.1289/ehp.1408094] [PMID] [PMCID]

Boyacioglu M, Turgut H, Akgullu C, Eryilmaz U, Kum C, Onbasili OA. The effect of L-Carnitine on oxidative stress responses of experimental contrast-induced nephropathy in rats. The Journal of Veterinary Medical Science. 2014; 76(1):1-8. [DOI:10.1292/jvms.13-0202] [PMID] [PMCID]

Ozsoy S, Ozsoy B, Ozyildiz Z, Aytekin I. Protective effect of L-Carnitine on experimental lead toxicity in rats: A clinical, histopathological and immunohistochemical study. Biotech Histochem. 2011; 86(6):436-43. [DOI:10.3109/10520295.2010.529825] [PMID]

Xiang Y, Piao S, Zou H, Jin J, Fang M, Lei D, et al. L-Carnitine protects against cyclosporine-induced pancreatic and renal injury in rats. Transplantation Proceedings. 2013; 45(8):3127-34. [DOI:10.1016/j.transproceed.2013.08.041] [PMID]

Aydogdu N, Atmaca G, Yalcin O, Taskiran R, Tastekin E, Kaymak K. Protective effects of L-Carnitine on myoglobinuric acute renal failure in rats. Clinical and Experimental Pharmacology and Physiology. 2006; 33(1):119-24. [DOI:10.1111/j.1440-1681.2006.04336.x] [PMID]

Ghalwash M, Elmasry A, El-Adeeb N. Effect of L-Carnitine on the skeletal muscle contractility in simvastatin-induced myopathy in rats. Journal of Basic and Clinical Physiology and Pharmacology. 2018; 29(5):483-91. [DOI:10.1515/jbcpp-2017-0156] [PMID]

Heidari R, Jafari F, Khodaei F, Shirazi Yeganeh B, Niknahad H. Mechanism of Valproic acid‐induced Fanconi syndrome involves mitochondrial dysfunction and oxidative stress in rat kidney. Nephrology. 2018; 23(4):351-61. [DOI:10.1111/nep.13012] [PMID]

Collins HL, Drazul Schrader D, Sulpizio AC, Koster PD, Williamson Y, Adelman SJ, et al. L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE−/− Transgenic mice expressing CETP. Atherosclerosis. 2016; 244:29-37. [DOI:10.1016/j.atherosclerosis.2015.10.108] [PMID]

Kopple JD, Ding H, Letoha A, Ivanyi B, Qing DPY, Dux L, et al. L-Carnitine ameliorates gentamicin‐induced renal injury in rats. Nephrology Dialysis Transplantation. 2002; 17(12):2122-31. [DOI:10.1093/ndt/17.12.2122]

Boonsanit D, Kanchanapangka S, Buranakarl C. L-Carnitine ameliorates doxorubicin‐induced nephrotic syndrome in rats. Nephrology. 2006; 11(4):313-20. [DOI:10.1111/j.1440-1797.2006.00592.x] [PMID]

Chang B, Nishikawa M, Sato E, Utsumi K, Inoue M. L-Carnitine inhibits Cisplatin-induced injury of the kidney and small intestine. Archives of Biochemistry and Biophysics. 2002; 405(1):55-64. [DOI:10.1016/S0003-9861(02)00342-9]

Origlia N, Migliori M, Panichi V, Filippi C, Bertelli A, Carpi A, et al. Protective effect of L-propionylcarnitine in chronic cyclosporine-a induced nephrotoxicity. Biomedicine & Pharmacotherapy. 2006; 60(2):77-81. [DOI:10.1016/j.biopha.2005.06.014] [PMID]

Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clinical Chemistry. 1990; 36(8):1440-3. [PMID]

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979; 95(2):351-8. [DOI:10.1016/0003-2697(79)90738-3]

Ellaman G. Tissue sulfhydryl group. Archives of Biochemistry and Biophysics. 1959; 82(1):70-7. [DOI:10.1016/0003-9861(59)90090-6]

Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clinical Chemistry. 1988; 34(3):497-500. [PMID]

Aebi H. [13] Catalase in vitro. Methods in Enzymology. 1984; 105:121-6. [DOI:10.1016/S0076-6879(84)05016-3]

Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and Biophysical Research Communications. 1976; 71(4):952-8. [DOI:10.1016/0006-291X(76)90747-6]

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry. 1951; 193(1):265-75. [PMID]

Liu X, Zhong F, Tang Xl, Lian Fl, Zhou Q, Guo Sm, et al. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: A metabolomic analysis. Acta Pharmacologica Sinica. 2014; 35(5):697-706. [DOI:10.1038/aps.2013.186] [PMID] [PMCID]

Bonomini M, Di Liberato L, Del Rosso G, Stingone A, Marinangeli G, Consoli A, et al. Effect of an L-Carnitine–Containing Peritoneal Dialysate on Insulin sensitivity in patients treated with CAPD: A 4-Month, prospective, multicenter randomized trial. American Journal of Kidney Diseases. 2013; 62(5):929-38. [DOI:10.1053/j.ajkd.2013.04.007] [PMID]

Edres HA, Taha NM, Mandour AW, Lebda MA. Impact of L-Carnitine on Bisphenol A-induced kidney damage in rats. Alexandria Journal for Veterinary Sciences. 2018; 56(1):11-7. [DOI:10.5455/ajvs.283744]

Mafra D, Borges NA, de Franca Cardozo LFM, Anjos JS, Black AP, Moraes C, et al. Red meat intake in chronic kidney disease patients: Two sides of the coin. Nutrition. 2018; 46:26-32. [DOI:10.1016/j.nut.2017.08.015] [PMID]

Sener G, Paskaloglu K, Satiroglu H, Alican I, Kaçmaz A, Sakarcan A. L-Carnitine ameliorates oxidative damage due to chronic renal failure in rats. Journal of Cardiovascular Pharmacology. 2004; 43(5):698-705. [DOI:10.1097/00005344-200405000-00013] [PMID]

Marcovina SM, Sirtori C, Peracino A, Gheorghiade M, Borum P, Remuzzi G, et al. Translating the basic knowledge of mitochondrial functions to metabolic therapy: Role of L-Carnitine. Translational Research. 2013; 161(2):73-84. [DOI:10.1016/j.trsl.2012.10.006] [PMID] [PMCID]

Armaly Z, Qader AA, Jabbour A, Hassan K, Ramadan R, Bowirrat A, et al. Effects of carnitine on oxidative stress response to intravenous iron administration to patients with CKD: Impact of haptoglobin phenotype. BMC Nephrology. 2015; 16:135. [DOI:10.1186/s12882-015-0119-0] [PMID] [PMCID]

Caloglu M, Yurut Caloglu V, Durmus Altun G, Oz Puyan F, Ustun F, Cosar Alas R, et al. Histopathological and scintigraphic comparisons of the protective effects of L-Carnitine and amifostine against radiation-induced late renal toxicity in rats. Clinical and Experimental Pharmacology and Physiology. 2009; 36(5-6):523-30. [DOI:10.1111/j.1440-1681.2008.05103.x] [PMID]

Nasri H, Abedi Gheshlaghi Z, Rafieian Kopaei M. Curcumin and kidney protection; current findings and new concepts. Acta Persica Pathophysiologica. 2018; 1:e01-6.

Samir SM, Abbas AM, Safwat SM, Elserougy HG. Effect of L-Carnitine on diabetes-induced changes of skeletal muscles in rats. Journal of Basic and Clinical Physiology and Pharmacology. 2018; 29(1):47-59. [DOI:10.1515/jbcpp-2016-0185] [PMID]

Rani PJA, Panneerselvam C. Effect of L-Carnitine on brain lipid peroxidation and antioxidant enzymes in old rats. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2002; 57(4):B134-B7. [DOI:10.1093/gerona/57.4.B134] [PMID]

Arslan E, Milcan A, Ünal S, Demirkan F, Polat A, Bagdatoglu Ö, et al. The effects of carnitine on distally-burned dorsal skin flap: An experimental study in rats. Burns. 2003; 29(3):221-7. [DOI:10.1016/S0305-4179(02)00305-4]

Ergün O, Ulman C, Kiliçalp AS, Ulman I. Carnitine as a preventive agent in experimental renal ischemia-reperfusion injury. Urological Research. 2001; 29(3):186-9. [DOI:10.1007/s002400100176] [PMID]

Lv S, Cheng J, Sun A, Li J, Wang W, Guan G, et al. Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting oxidative stress. Diabetes Research and Clinical Practice. 2014; 104(1):143-54. [DOI:10.1016/j.diabres.2014.01.011] [PMID]

Liu CM, Ma JQ, Sun YZ. Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxicology and Applied Pharmacology. 2012; 258(3):330-42. [DOI:10.1016/j.taap.2011.11.015] [PMID]

Liu CM, Ma JQ, Sun YZ. Quercetin protects the rat kidney against oxidative stress-mediated DNA damage and apoptosis induced by lead. Environmental Toxicology and Pharmacology. 2010; 30(3):264-71. [DOI:10.1016/j.etap.2010.07.002] [PMID]




DOI: https://doi.org/10.22037/ijmtfm.v0i0.21730