Antioxidant Activity of Lipoic Acid on Cyclosporine A-Induced Physiological Changes to the Kidneys in Male Albino Rats

Authors

  • Nura I. Al-Zail Zoology Department, Faculty of Science, Omar Al-Mukhtar University, Libya

DOI:

https://doi.org/10.54172/mjsc.v32i1.89

Keywords:

Lipoic acid, cyclosporine A, oxidative stress, renal toxicity

Abstract

Cyclosporine A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity and hepatotoxicity. This study aimed to assess the protective role of lipoic acid (LA) on kidney toxicity of male albino rats induced by cyclosporine (CsA). Forty adult male rats were allocated into four groups: Group (I) served as a control group. Group (II); received treatments orally with CsA (25 mg/kg b.w.), daily for 3 weeks. Group III: (Recovery CsA group):  treated orally with CsA (25 mg/kg b.w.), daily for 3 weeks, then recovered for another 3 weeks. Group IV (LA and CsA group):  received LA (100 mg/kg b. w.) orally 1 h before treatment by CsA (25 mg/kg b. w.) daily for 3 weeks. The results indicated that treatment of CsA caused a significant elevation in the concentrations of serum urea, creatinine, and uric acid which indicate injury to the kidney function. Renal malondialdehyde (MDA) concentration was markedly increased reflecting increased lipid peroxidation, whereas, reduced glutathione (GSH) and superoxide dismutase (SOD) were significantly decreased.  On the other hand, LA plus CsA dose-dependently inhibited activities of serum urea, creatinine, and uric acid. The administration of LA plus CsA exhibited significant reduction in lipid peroxidation while GSH content and SOD activity were enhanced significantly which reflect an improvement in renal toxicity. In conclusion, the results indicated a negative role of CsA on kidney function and oxidative stress in induction toxicity, suggested Thus, Lipoic acid play a positive role on toxicity of kidney induced by cyclosporine A.

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References

Agar, N. Y., Golby A. J., Ligon K. L., Norton I., Mohan V., Wiseman J. M., Tannenbaum A., and Jolesz F. A. (2011). Development of stereotactic mass spectrometry for brain tumor surgery. Neurosurgery 68(2):280-290. DOI: https://doi.org/10.1227/NEU.0b013e3181ff9cbb

Ajala, A. M., Goodwin J. A., Goodwin S. R., and Josephson G. D. (2008). Undiagnosed Graves' Disease contributing to sleep disordered breathing in a child undergoing adenotonsillectomy. Pediatric Anesthesia 18(4):358-359. DOI: https://doi.org/10.1111/j.1460-9592.2008.02482.x

Amudha, G., Josephine A., and Varalakshmi P. (2006). Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A. Clinica chimica acta 372(1):134-139. DOI: https://doi.org/10.1016/j.cca.2006.03.036

Barham, D., and Trinder P. (1972). An improved colour reagent for the determination of blood glucose by the oxidase system. Analyst 97(1151):142-145. DOI: https://doi.org/10.1039/an9729700142

Burdmann, E. A., Andoh T. F., Yu L., and Bennett W. M. 2003. Cyclosporine nephrotoxicity. Pages 465-476 in Seminars in nephrology. Elsevier. DOI: https://doi.org/10.1016/S0270-9295(03)00090-1

Chapman, J. R., and Nankivell B. J. (2006). Nephrotoxicity of ciclosporin A: short-term gain, long-term pain? Nephrology Dialysis Transplantation 21(8):2060-2063. DOI: https://doi.org/10.1093/ndt/gfl219

Chen, S., and Le W. (2006). Neuroprotective therapy in Parkinson disease. American journal of therapeutics 13(5):445-457. DOI: https://doi.org/10.1097/01.mjt.0000174353.28012.a7

Connell, B. J., and Saleh T. M. (2012). Co-administration of apocynin with lipoic acid enhances neuroprotection in a rat model of ischemia / reperfusion. Neuroscience letters 507(1):43-46. DOI: https://doi.org/10.1016/j.neulet.2011.11.047

Constantinescu, A., Tritschler H., and Packer L. (1994). alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. Biochemistry and molecular biology international 33 (4) :669-679.

Fawcett, J., and Scott J. (1960). A rapid and precise method for the determination of urea. Journal of clinical pathology 13(2):156-159. DOI: https://doi.org/10.1136/jcp.13.2.156

Fogo, A., Hellings S. E., Inagami T., and Kon V. (1992). Endothelin receptor antagonism is protective in in vivo acute cyclosporine toxicity. Kidney international 42(3):770-774. DOI: https://doi.org/10.1038/ki.1992.346

Forbes, J. M., Coughlan M. T., and Cooper M. E. (2008). Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57(6):1446-1454. DOI: https://doi.org/10.2337/db08-0057

Garcia-Cohen, E.-C., Marin J., Diez-Picazo L. D., Baena A. B., Salaices M., and Rodriguez-Martinez M. A. (2000). Oxidative stress induced by tert-butyl hydroperoxide causes vasoconstriction in the aorta from hypertensive and aged rats: role of cyclooxygenase-2 isoform. Journal of Pharmacology and Experimental Therapeutics 293(1):75-81.

Hagar, H. H., El Etter E., and Arafa M. (2006). Taurine attenuates hypertension and renal dysfunction induced by cyclosporine A in rats. Clinical and experimental pharmacology and physiology 33(3):189-196. DOI: https://doi.org/10.1111/j.1440-1681.2006.04345.x

Han, D., Handelman G., Marcocci L., Sen C. K., Roy S., Kobuchi H., Tritschler H. J., Flohé L., and Packer L. (1997). Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 6(3):321-338. DOI: https://doi.org/10.1002/biof.5520060303

Huong, D. T. T., and Ide T. (2008). Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. British journal of nutrition 100(1):79-87. DOI: https://doi.org/10.1017/S0007114507876227

Jalali-Nadoushan, M., and Roghani M. (2013). Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism. Brain research 1505(68-74. DOI: https://doi.org/10.1016/j.brainres.2013.01.054

Khan, M., Shobha J. C., Mohan I. K., Rao Naidu M. U., Prayag A., and Kutala V. K. (2006).Spirulina attenuates cyclosporine ‐induced nephrotoxicity in rats. Journal of applied toxicology 26(5):444-451. DOI: https://doi.org/10.1002/jat.1159

Koh, J.-M., Lee Y.-S., Byun C.-H., Chang E.-J., Kim H., Kim Y. H., Kim H.-H., and Kim G. S. (2005). α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells. Journal of endocrinology 185(3):401-413. DOI: https://doi.org/10.1677/joe.1.05995

Lexis, L. A., Fassett R. G., and Coombes J. S. (2006). α‐Tocopherol and α‐Lipoic Acid Enhance the Erythrocyte Antioxidant Defence in Cyclosporine A‐Treated Rats. Basic & clinical pharmacology & toxicology 98(1):68-73. DOI: https://doi.org/10.1111/j.1742-7843.2006.pto_222.x

Liu, J., Head E., Gharib A. M., Yuan W., Ingersoll R. T., Hagen T. M., Cotman C. W., and Ames B. N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-α-lipoic acid. Proceedings of the National Academy of Sciences 99(4):2356-2361. DOI: https://doi.org/10.1073/pnas.261709299

Malinska, D., and Winiarska K. (2005). Kwas liponowy – charakterystykai zastosowanie w terapii* Lipoic acid: Characteristics and therapeutic application. Postepy Hig.Med. Dosw 59 (535-543.

Marangon, K., Devaraj S., Tirosh O., Packer L., and Jialal I. (1999). Comparison of the effect of α-lipoic acid and α-tocopherol supplementation on measures of oxidative stress. Free Radical Biology and Medicine 27(9):1114-1121. DOI: https://doi.org/10.1016/S0891-5849(99)00155-0

Marklund, S. L. (1985). Superoxide dismutase isoenzymes in tissues and plasma from New Zealand black mice, nude mice and normal BALB/c mice. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 148(1):129-134. DOI: https://doi.org/10.1016/0027-5107(85)90216-7

Mohamadin, A., El-Beshbishy H., and El-Mahdy M. (2005). Green tea extract attenuates cyclosporine A-induced oxidative stress in rats. Pharmacological research 51(1):51-57. DOI: https://doi.org/10.1016/j.phrs.2004.04.007

Morel, P., Sutherland D. E., Almond P. S., Stöblen F., Matas A. J., Najarían J. S., and Dunn D. L. (1991). Assessment of renal function in type I diabetic patients after kidney, pancreas, or combined kidney - pancreas transplantation. Transplantation 51(6):1184-1189. DOI: https://doi.org/10.1097/00007890-199106000-00008

Nankivell, B. J., Chapman J. R., Bonovas G., and Gruenewald S. M. (2004). Oral cyclosporine but not tacrolimus reduces renal transplant blood flow. Transplantation 77(9) :1457-1459. DOI: https://doi.org/10.1097/01.TP.0000121196.71904.E0

Pallet, N., Rabant M., Xu-Dubois Y.-C., LeCorre D., Mucchielli M.-H., Imbeaud S., Agier N., Hertig A., Thervet E., and Legendre C. (2008). Response of human renal tubular cells to cyclosporine and sirolimus: a toxicogenomic study. Toxicology and applied pharmacology 229(2):184-196. DOI: https://doi.org/10.1016/j.taap.2008.01.019

Scott, B. C., Aruoma O. I., Evans P. J., O'neill C., Van Der Vliet A., Cross C. E., Tritschler H., and Halliwell B. (1994). Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free radical research 20(2):119-133. DOI: https://doi.org/10.3109/10715769409147509

Sedlak, J., and Lindsay R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry 25(192-205. DOI: https://doi.org/10.1016/0003-2697(68)90092-4

Seeling, H., and Wust H. (1969). Colorimetric method for determination of creatinine. Arztl. Lab 15(34.

Shay, K. P., Moreau R. F., Smith E. J., Smith A. R., and Hagen T. M. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta (BBA)-General Subjects 1790(10):1149-1160. DOI: https://doi.org/10.1016/j.bbagen.2009.07.026

Singh, U., and Jialal I. (2008). Retracted: Alpha-lipoic acid supplementation and diabetes. Nutrition reviews 66(11):646-657. DOI: https://doi.org/10.1111/j.1753-4887.2008.00118.x

Sivaprasad, R., Nagaraj M., and Varalakshmi P. (2004). Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. The Journal of nutritional biochemistry 15(1):18-23. DOI: https://doi.org/10.1016/j.jnutbio.2003.09.001

Smith, A., Shenvi S., Widlansky M., Suh J., and Hagen T. (2004). Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Current medicinal chemistry 11(9):1135-1146. DOI: https://doi.org/10.2174/0929867043365387

Tirkey, N., Kaur G., Vij G., and Chopra K. (2005).Curcumin, adiferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys. BMC pharmacology 5(1):15. DOI: https://doi.org/10.1186/1471-2210-5-15

Uchiyama, M., and Mihara M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Analytical biochemistry 86(1):271-278. DOI: https://doi.org/10.1016/0003-2697(78)90342-1

Wang, Y., Wu Y., Luo K., Liu Y., Zhou M., Yan S., Shi H., and Cai Y. (2013). The protective effects of selenium on cadmium-induced oxidative stress and apoptosis via mitochondria pathway in mice kidney. Food and chemical toxicology 58(61-67. DOI: https://doi.org/10.1016/j.fct.2013.04.013

Wollin, S. D., and Jones P. J. (2003). α-Lipoic acid and cardiovascular disease. The Journal of nutrition 133(11):3327-3330. DOI: https://doi.org/10.1093/jn/133.11.3327

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Published

2017-06-30

How to Cite

Al-Zail, N. I. (2017). Antioxidant Activity of Lipoic Acid on Cyclosporine A-Induced Physiological Changes to the Kidneys in Male Albino Rats. Al-Mukhtar Journal of Sciences, 32(1), 9–16. https://doi.org/10.54172/mjsc.v32i1.89

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