Comparison of the Species"‘Sensitive Effects of Different Dosages of Calcium and Verapamil on Gentamicin"‘Induced Nephrotoxicity in Rats and Rabbits

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Keywords:

Calcium, gentamicin, nephrotoxicity, rabbits, rats, verapamil

Abstract

Aim: To compare the effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. Materials and Methods: Rabbits and rats of either sex in weight range of 1.5–2.5 kg and 175–225 g, respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5 g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day i.m. were administered for 6 days in either species containing 7 groups. Blood urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for histopathplogical examination and kidney superoxide dismutase levels (SOD) were measured. Statistical analysis was done using student's unpaired t-test, analysis of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was considered significant. Results: The results showed that calcium was able to reverse significantly increased BUN, serum creatinine, urine protein, and reduced kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose-dependent manner while verapamil had no protective or nephrotoxic effect. Conclusion: Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals. There was no species-sensitive variation in reversal of nephrotoxicity by calcium in rats and rabbits.

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Published

2018-06-04

How to Cite

Patil, A. N., Arora, T., Desai, A., & Dhar Tripathi, C. (2018). Comparison of the Species"‘Sensitive Effects of Different Dosages of Calcium and Verapamil on Gentamicin"‘Induced Nephrotoxicity in Rats and Rabbits. Toxicology International, 21(3), 225–231. Retrieved from http://informaticsjournals.com/index.php/toxi/article/view/21024

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Section

Original Research
Received 2018-04-27
Accepted 2018-04-27
Published 2018-06-04

 

References

Humes HD. Aminoglycoside nephrotoxicity. Kidney Int 1988;33:900"‘11.

Jha V, Malhotra HS, Sakhaja V, Chugh KS. Spectrum of hospital acquired acute renal failure in the developing countries"‘"‘Chandigarh study. Q J Med 1992;83:497"‘505.

Eisenberg JM, Koffer H, Glick HA, Connell ML, Loss LE, Talbot GH, et al. What is the cost of nephrotoxicity associated with aminoglycoside? Ann Intern Med 1987;107:900"‘9.

Vandewalle A, Farman N, Morin JP, Fillastre JP, Hatt PY, Bonvalet JP. Gentamicin incorporation along the nephron: Autoradiographic study on isolated tubules. Kidney Int 1981;19:529"‘39.

Sandoval R, Leiser J, Molitoris BA. Aminoglycoside antibiotics traffic to the Golgi complex in LLC"‘PK1 cells. J Am Soc Nephrol 1998;9:167"‘74.

Kadkhodaee M, Khastar H, Faghihi M, Ghaznavi R, Zahmatkesh M. Effects of co"‘supplementation of vitamins E and C on gentamicin"‘induced nephrotoxicity in rat. Exp Physiol 2005;90:571"‘6.

Kadkhodaee M, Khastar H, Arab HA, Ghaznavi R, Zahmatkesh M, Mahdavi"‘Mazdeh M. Antioxidant vitamins preserve superoxide dismutase activities in gentamicin"‘induced nephrotoxicity. Transplant Proc 2007;39:864"‘5.

Maldonado PD, Barrera D, Rivero I, Mata R, Medina"‘Campos ON, Hernandez"‘Pando R, et al. Antioxidant S"‘allylcysteine prevents gentamicin"‘induced oxidative stress and renal damage. Free Radic Biol Med 2003;35:317"‘24.

Pedraza"‘Chaverri J, Maldonado PD, Barrera D, Ceron A, Medina"‘Campos ON, Hernandez"‘Pando R. Protective effect of diallyl sulfide on oxidative stress and nephrotoxicity induced by gentamicin in rats. Mol Cell Biochem 2003;254:125"‘30.

Jeyanthi T, Subramanian P. Protective effect of Withania somnifera root powder on lipid peroxidation and antioxidant status in gentamicin"‘induced nephrotoxic rats. J Basic Clin Physiol Pharmacol 2010;21:61"‘78.

Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia"‘reperfusion"‘induced oxidative damage in rats. J Pharm Pharm Sci 2005;8:387"‘93.

Yaman I, Balikci E. Protective effects of nigella sativa against gentamicin"‘induced nephrotoxicity in rats. Exp Toxicol Pathol 2010;62:183"‘90.

Carlier MB, Laurent G, Claes PJ, Vanderhaeghe HJ, Tulkens PM. Inhibition of lysosomal phospholipases by aminoglycoside antibiotics: In vitro comparative studies. Antimicrob Agents Chemother 1983;23:440"‘9.

Watson AJ, Gimenez LF, Klassen DK, Stout RL, Whelton A. Calcium channel blockade in experimental aminoglycoside nephrotoxicity. J Clin Pharmacol 1987;27:625"‘7.

Ali BH, Al"‘Qarawi AA, Mousa HM. The effect of calcium load and the calcium channel blocker verapamil on gentamicin nephrotoxicity in rats. Food Chem Toxicol 2002;40:1843"‘7.

Stojiljkovic N, Veljkovic S, Mihailovic D, Stoiljkovic M, Radovanovic D, Randelovic P. The effect of calcium channel blocker verapamil on gentamicin nephrotoxicity in rats. Bosn J Basic Med Sci 2008;8:170"‘6.

Stojilkovic N, Stoiljkovic M, Mihailovic D, Randjelovic P, Ilic S, Ignjatovic G, et al. Beneficial effects of calcium oral coadministration in gentamicin"‘induced nephrotoxicity in rats. Ren Fail 2012;34:622"‘7.

Quarum M, Houghton DC, Gilbert DN, McCarron DA, Bennett WM. High calcium intake modifies experimental gentamicin nephrotoxicity. Clin Res 1983;31:76A.

Das K, Samanta L, Chainy GB. A modified spectrophotometric assay of superoxide dismutase using nitrite formation by superoxide radicals. Indian J Biochem Biophys 2000; 37:201"‘4.

Hostetter TH, Brenner BM. Renal circulatory and nephron function in experimental acute renal failure. In: Brenner BM, Lazarus JM, editors. Vol. 6: Acute Renal Failure, 2nd ed. New York: Churchill Livingstone; 1988. p. 66"‘88.

Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative Group. Crit Care 2004;8:R204"‘12.

Khan KN, Alden CL. In: Haschek WM, Rousseaux CG, Wallig MA, editors. Kidney. Handbook of Toxicologic Pathology. Vol 2. 2nd ed. 2002. p.255"‘330.

Niemczyk S, Ludwicka A, Groniowski M, Lewandowski Z, Hasse Z.Nephrotoxicity of aminoglycosides. I: Preventive intraperitoneal calcium administration. Pol Arch Med Wewn 1991;85:1"‘11.

Tamir A, Aladjem M, Bogin E. The effect of oral calcium load or verapamil on gentamicin"‘induced nephrotoxicity. J Clin Chem Clin Biochem 1989;27:847"‘50.

Walker PD, Shah SV. Evidence suggesting a role for hydroxyl radical in gentamicin induced acute renal failure in rats. J Clin Invest 1988;81:334"‘41.

Toubeau G, Laurent G, Carlier MB, Abid S, Maldague P, Heuson"‘Stiennon JA, et al. Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses: A comparative biochemical and morphometric study. Lab Invest 1986;54:385"‘93.

Riviere JE, Coppoc GL, Hinsman EJ, Carlton WW, Traver DS. Species dependent gentamicin pharmacokinetics and nephrotoxicity in the young horse. Fundam Appl Toxicol 1983;3:448"‘57.

Ali BH, Bashir AA. Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal"‘5"‘phosphate on gentamicin"‘induced nephrotoxicity in the rat. Gen Pharmacol 1993;24:1279"‘83.

Schneider M, Valentine S, Clarke GM, Newman MA, Peacock J. Acute renal failure in cardiac surgical patients potentiated by gentamicin and calcium. Anaesth Intensive Care 1996;24:647"‘50.

Humes HD, Sastrasinh M, Weinberg JM. Calcium is a competitive inhibitor of gentamicin"‘renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity. J Clin Invest 1984;73:134"‘47.

Perez de la Cruz MJ, Cadoringa R, Ochoa MC, Albarran I, Herrero"‘Vanrell R, Pastoriza P. Chronopharmacokinetics and calcium in the prevention of gentamicin"‘induced nephrotoxicity in rabbits. Biopharm Drug Dispos 1998;19:407"‘12.

Rodriguez"‘Barbero A, Bosque E, Gonzalez"‘Buitrago JM, Garcia"‘Bastos JL, Lopez"‘Novoa JM. Gentamicin nephrotoxicity in rats is not modified by verapamil. Arch Int Physiol Biochim Biophys 1993;101:395"‘7.