Livolin Forte Ameliorates Cadmium-Induced Kidney Injury in Wistar Rats

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The kidney, which is an integral part of the drug excretion system, was reported as one of the targets of cadmium toxicity. Early events of cadmium toxicity in the cell include a decrease in cell membrane fluidity, breakdown of its integrity, and impairment of its repair mechanisms. Phosphatidylcholine and vitamin E have a marked fluidizing effect on cellular membranes. We hypothesized that Livolin forte (LIV) could attenuate kidney damage induced by cadmium in rats. Twenty-five adult male Wistar rats were divided into five groups of five rats each: group I (control group) received 0.3 ml/kg/day of propylene glycol for six weeks; group II was given 5 mg/kg/day of cadmium (Cd) i.p for 5 consecutive days; group III rats were treated in a similar way as group II but were allowed a recovery period of 4 weeks; group IV was treated with LIV (5.2 mg/kg/day) for a period of 4 weeks after inducing renal injury with Cd similarly to group II; and group V was allowed a recovery period of 2 weeks after a 4-week LIV treatment (5.2 mg/kg/day) following Cd administration. A significant increase in plasma creatinine, urea, uric acid, and TBARS were observed in groups II and III compared to the control rats. Significant reductions in total protein, glucose, and GSH activity were also recorded. The urine concentrations of creatinine, urea, and uric acid in groups II and III were significantly lower than the control group. Th is finding was accompanied by a significant decrease in creatinine and urea clearance. Post-treatment with LIV caused significant decreases in plasma creatinine, urea, uric acid, and TBARS. Significant increases in total protein, glucose, and GSH activity of groups IV and V were observed compared to group II. A significant increase in urine concentrations of creatinine, urea, and uric acid and significant decreases in total protein, glucose, and GSH activity were observed in groups IV and V compared to group II. Photomicrographs of the rat kidneys in groups IV and V showed an improvement in the histology of their renal tissue when compared to group II, with features similar to the control rats. Additionally, group III showed an improvement in the histoarchitecture of the kidney compared with group II, although occasional atrophy of some glomeruli and shrinking of renal corpuscles was observed.

In conclusion, the results of this study indicated that LIV administration ameliorated Cd-induced kidney injury in rats. Thus, LIV represents a prospective therapeutic choice to prevent kidney injury inflicted by Cd exposure.

1. Hooser SB (2007). Cadmium In: Veterinary Toxicology, Gupta RC. (Ed.). Macmillan Company, USA. p. 422-427.

2. Cinar M. Cadmium and effects at biological system (2003). Veterinarium. 14, 79-84.

3. El-Sokkary GH, Awadalla EA. (2011). The protective role of vitamin C against cerebral and pulmonary damage induced by cadmium chloride in male adult albino rat. Open Neuroendocrinol. J. 4, 1-8.

4. Gulyasar T, Aydogbu N, Cakina S, Siphali T, Kaymar K, et al. (2009). Trace element in rat model of cadminm toxicity: The effects of taurine melatonin and N acetylcysteine. Trakya Univ Tip Fak Derg. 27(1), 23-27.

5. Karimi MM, Sani MJ, Mahmudabadi AZ, Sani AJ, Khatibi SR. (2012). Effect of acute toxicity of cadmium in mice kidney cells. Iran J Toxicol. 6(18), 691-698.

6. Lasshmi GD, Kumar PR, Bharavi K, Annapura P, et al. (2012). Protective effect of tribulus terrestries linn on liver and kidney in cadmium. Indian J Exper Biol. 50, 141-146.

7. Williams F, Robertson R, Roworth M. (1999). Scottish Centre for Infection and Environmental Health. Detailed Profile of 25 Major Organic and Inorganic Substances. 1st ed. Glasgow: SCEIH.

8. Minto RE, Adhikari PR, Lorigan GA. (2004). A 2H solid state NMR spectroscopic investigation of biomimetic bicelles containing cholesterol and polyunsaturated phosphatidylcholine. Chem Phys Lipids. 132, 55-64.

9. Zamana N. (2004). Alteration of polyunsaturated fatty acid status and metabolism in health and disease. Reprod Nutr Dev. 44, 273-232.

10. Sekharam KM, Patel JM, Block ER. (1990). Effect of polyunsaturated fatty acids and phospholipids on (sup 3 H)-vitamin E incorporation into pulmonary artery endothelial cell membranes. J Cell Physiol. 145, 555-563.

11. Traber MG, Sies H. (1996). Vitamin E in Humans: Demand and Delivery. Annu Rev Nutr. 16, 321-347.

12. Svintsitskiĭ AS, Revenok EN, Solov’eva GA, Tkachuk AI. (2003). Assessment of effectiveness of livolin forte in the treatment of patient with steatohepatitis. Lik Sprava. 2, 76-80

13. Otegbayo JA, Kuti MA, Ogunbode O, Irabor AE, Adewole IF. (2012). Livolin ameliorates elevations in alanine transaminase in HIV infected patients commencing highly active antiretroviral therapy. Afr J Med Sci. 41, 417-422.

14. Nwozo SO, Osunmadewa DA, Oyinloye BE. (2014). Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats. J Integr Med. 12(1), 59-65.

15. Beutler E, Duron O, Kelly BM. (1963). Improved method for determination of blood glutathione. 61, 882-8.

16. Lowry OH, Rosenbrough NJ, Farr A. (1951). Randall RJ. Protein measurement with the Folin Phenol reagent. J Biol Chem. 193, 265-75.

17. Holme DJ, Peck H. (1998). Analytical Biochemistry, 3rd ed. Longman, New York.

18. Ohkawa H, Ohishi N, Yagi K. (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Annals Biochem. 95, 351-358.

19. Shim JA. (2008). Effect of Chlorella intake on Cadmium metabolism in rats. Master thesis. Ewha Womans University, Seoul. Republic of Korea.

20. Choi JH, Rhee SJ. (2001). Effects of green tea catechin on cadmium accumulation in chronic cadmium poisoned rats. Korean J Nutr. 34, 384-392.

21. Horiguchi H, Sato M, Konno N, Fukushima M. (1996). Long term cadmium exposure induces anaemia in rats through hypoinduction of erythropoietin in the kidney. Arch Toxicol. 71, 11-19.

22. Josthna P, Geetharathan T, Sujatha P, Deepika G. (2012). Accumulation of lead and cadmium in the organs and tissues of albino rat. Int J Pharm Life Sci. 3(12), 2186-2189.

23. Cummings DE and Joost O. (2007). “Gastrointestinal regulation of food intake, ”. J Clin Invest. 117, 13-23.

24. Kaltreider RC, Davis AM, Lariviere JP, Hamilton JW. (2001). Arsenic alters the function of the glucocorticoid receptor as a transcription factor. Environ Health Persp. 109, 245-251.

25. Eriyamremu GE, Asagba SO, Onyeneke EC, Adaikpo MA. (2005). Changes in carboxypeptidase A, dipeptidase and Na+/K+ ATPase activities in the intestine of rats orally exposed to different doses of cadmium. Bio- Metals. 18, 1-6.

26. Erdogan Z, Erdogan S, Celik S, Unlu V. (2005). Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers. Biol Trace Elem Res. 104, 19-31.

27. Yoshida Y, Ito N, Shimakawa S, Niki E. (2003). Susceptibility of plasma lipids to peroxidation. Biochem Biophys Res Commun. 305, 747-53.

28. Murphy VA. (1996). Cadmium: acute and chronic neurological disorders. In: Yasui M, Strong MJ, Ota K and Verity MA (Editors), Mineral and Metal Neurotoxicology. CRC Press, Boca Raton. 1996; 229-240.

29. Ige SF, Akhigbe RE, Adewale AA, Badmus JA, Olaleye SB, Ajao FO, Saka WA Owolabi OQ. (2010). Effect of Allium Cepa (Onion) extract on cadmium-induced nephrotoxicity in rats. 1-7.

30. Ellison DH. (2008). “Atlas of kidney diseases” Colorado: Blackwell publishing.

31. Pitts RF. (1974). Physiology of the Kidney and Body Fluid. 3rd edition. An Introductory Text. Year Book Medical Publishers, Incorporated, Chicago.

32. Crook MA. (2012). Clinical Biochemistry and Metabolic Medicine. 8th Edition. Hodder and Stoughton Ltd.

33. Goncalves JF, Fiorenza AM, Spanevello RM, Mazzanti CM, Bochi GV et al. (2010). N-acetylcysteine prevents memory deficits, the decrease in acetyl cholinesterase activity and oxidative stress in rats exposed to cadmium. Chem Biol Interact. 186, 53-60.

34. Preet S, Dua KK. (2011). Protective influence of dietary nutrients on antioxidant defense system in the blood of rats treated with Cadmium. Adv Applied Sci Res. 2, 69-78.

35. Ohno I. Relationship between hyperuricemia and chronic kidney disease. (2011). Nucleos Nucleot Nucl. 30, 1039-1044.

36. Kechrid Z, Dahdouh F, Djabar RM, Bouzerna N. (2006). Combined effect of water contamination with cobalt and nickel on metabolism of albino (Wistar) rats. Environ Health Sci Eng. 3(1), 65-69.

37. Sunderman FW, Jr . (1976)“ A review of the carcinogenicities of nickel, chromium and arsenic compounds in man and animals. “ Prev Med. 5, 279-294.

38. Massanyi P, Toman R, Valent M, Cupka P. (1995). Evaluation of selected parameters of a metabolic profile and levels of cadmium in reproductive organs of rabbits after an experimental administration. Acta Physiologica Hung. 83, 267-273.

39. L’Azou B, Dubus I, Ohayon-Courtes C, Camber J. (2002). Human glomerular mesangial IP15 cell line as a suitable model for in vitro cadmium cytotoxicity studies. Cell Biol Toxicol. 23, 267-278.

40. Rodriguez-Barbero A, L’Azou B, Camber J, Lopez-Novoa JM. (2000). Potential use of isolated glomeruli and cultured mesangial cells as in vitro models to assess nephrotoxicity. Cell Biol Toxicol. 16, 145-53.

41. Stohs SJ, Bagchi, D. (1995). Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med. 18, 321-336.

42. Waisberg M, Joseph P, Hale B, Beyersmann D. (2003). Molecular mechanisms of cadmium carcinogenesis. Toxicology. 192, 95-117.

43. Stohs SJ, Bagchi D, Hassoun E, Bagchi MM. (2000). Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol. 19, 201-213.

44. Traber MG, Atkinson, J. (2007). Vitamin E, antioxidant and nothing more. Free Radic. Biol. Med. 43, 4-15.

45. Brown LA. (2004). Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability? Alcol. 33, 191-197.

46. Larson RA. (1988). The antioxidants of higher plants. Phytochem. 27, 969-978.

47. Benzi G, Curti D, Marzatico F, Pastoris O. (1991). Agerelated acute depletion of cerebral glutathione by peroxidative stress. J Neurosci Res. 29(4), 527-32.

48. Aldana L, Tsutsumi V, Craigmill A, Silveira MI, De Mejia EG. (2001). α -Tocopherol modulates liver toxicity of the pyethroid cypermethrin. Toxicol Lett. 125, 107-116.

Serbian Journal of Experimental and Clinical Research

The Journal of Faculty of Medical Sciences, University of Kragujevac

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