AMIODARONE INDUCED OXIDATIVE STRESS IN STRESS - VULNERABLE ORGANS OF ADULT MALE RATS
Abstract
Objective: Amiodarone used as an antiarrhythmic agent bears a structural resemblance to thyroid hormones containing about one-third iodine by
weight. The pro-oxidant potentialities of amiodarone induced changes were studied.
Materials and Methods: Male adult Wister rats were divided into two groups of eight animals each, and amiodarone was supplemented orally
for 30 days against control. The urinary iodine content of both the groups was measured. Animals were sacrificed after completion of treatment;
investigated parameters were adrenal morphology and histology, adrenal Δ5 3β hydroxyl steroid dehydrogenase (HSD) and serum cortisol level.
Superoxide dismutase (SOD), catalase and lipid peroxidation (LPO) level were assayed in the liver, kidney and testis along with their histology. Serum
glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvate transaminase (SGPT) were measured. Obtained results were interpreted against
the control group of rats.
Results: Urinary iodine level was high after the amiodarone exposure. Hypertrophied cortex with enhanced Δ5 3β HSD activity in adrenal caused
elevated serum cortisol level. Amiodarone exposure had increased LPO level with a concomitant rise in catalase and SOD activities in liver, kidney and
testis in comparison to control (p<0.001). Simultaneously kidney showed shrinkage of the glomerulus, in liver the area surrounding the central canal
found disrupted and in the testis seminiferous tubules, and germ cells were disorganized in comparison to control. SGOT and SGPT level were found
elevated in the treated group.
Conclusion: Amiodarone exposure develops stress for the metabolism and deiodinization of amiodarone releasing excessive iodine in circulation
that in turn generates reactive oxygen species and free radicals resulting cellular damage of stress vulnerable organs.
Keywords: Amiodarone, Excess iodine, Hypertrophied adrenal, Cellular damage, Stress-vulnerable organs, Reactive oxygen species.
Downloads
References
Newman CM, Price A, Davies DW, Gray TA, Weetman AP.
Amiodarone and the thyroid: A practical guide to the management
of thyroid dysfunction induced by amiodarone therapy. Heart
;79(2):121-7.
Bonati M, Gaspari F, D’Aranno V, Benfenati E, Neyroz P, Galletti F,
et al. Physicochemical and analytical characteristics of amiodarone.
J Pharm Sci 1984;73(6):829-31.
Roberts M. Clinical utility and adverse effects of amiodarone therapy.
AACN Adv Crit Care 2010;21(4):333-8.
Rebrova TY, Afanasyev SA. Free radical lipid peroxidation during
amiodarone therapy for postinfarction cardiosclerosis. Bull Exp Biol
Med 2008;146(3):283-5.
Ursella S, Testa A, Mazzone M, Gentiloni SN. Amiodarone-induced
thyroid dysfunction in clinical practice. Eur Rev Med Pharmacol Sci
;10(5):269-78.
Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med
;118(7):706-14.
Delange F. The disorders induced by iodine deficiency. Thyroid
;4(1):107-28.
Ramachandran HD, Narasimhamurthy K, Raina PL. Effect of oxidative
stress on serum and antioxidant enzymes in liver and kidney of rats
and their modulation through dietary factors. Indian J Exp Biol
;40(9):1010-5.
Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS,
Lele RD. Free radicals and antioxidants in human health: Current status
and future prospects. J Assoc Physicians India 2004;52:794-804.
Many MC, Papadopoulos J, Martin C, Colin I, Denef JF. Iodine
induced cell damage in mouse hyperplastic thyroid is associated to lipid
peroxidation. In: Gordon A, Gross J, Hennermann G, editors. Progress
in Thyroid Research. Proceedings of the 10th International Thyroid
Conference. Rotterdam: The Hague A.A. Balkema Publishers; 1992.
p. 635-8.
Aggarwal D, Sharma M, Singla SK. The role of natural antioxidants as
potential therapeutic agent in nephrolithiasis. Asian J Pharm Clin Res
;6(3):48-53.
Chandra AK, Ghosh R, Chatterjee A, Sarkar M. Protection against
vanadium-induced testicular toxicity by testosterone propionate in rats.
Toxicol Mech Methods 2010;20(6):306-15.
Kolettis TM, Agelaki MG, Baltogiannis GG, Vlahos AP, Mourouzis I,
Fotopoulos A, et al. Comparative effects of acute vs. chronic oral
amiodarone treatment during acute myocardial infarction in rats.
Europace 2007;9(11):1099-104.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues
by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351-8.
Aebi H. Catalase. In: Bergmeyer HU, editor. Methods in Enzymatic
Analysis. New York: Academic Press; 1974. p. 673-8.
Marklund S, Marklund G. Involvement of the superoxide anion radical
in the autoxidation of pyrogallol and a convenient assay for superoxide
dismutase. Eur J Biochem 1974;47(3):469-74.
Talaley P. Hydroxy steroid dehydrogenase. In: Colowick SP, Kaplan NO,
editors. Method in Enzymology. 5th ed. NewYork: Academic Press; ???.
p. 512.
Glick D, Vonredlich D, Levine S. Fluorometric determination of
corticosterone and cortisol in 0.02-0.05 milliliters of plasma or
submilligram samples of adrenal tissue. Endocrinology 1964;74:653-5.
Karmarkar MG, Pandav CS, Krishnamachari KA. Principle and
procedure for iodine estimation. In: A Laboratory Manual. New Delhi:
Indian Council of Medical Research; 1986. p. 1-14.
Lowry OH, Rosenburg NJ, Farr AL, Randall RJ. Protein measurement
from phenol reagent. J Biol Chem 1951;193:265-75.
Harris L, McKenna WJ, Rowland E, Holt DW, Storey GC, Krikler DM.
Side effects of long-term amiodarone therapy. J Am Heart Assoc
;67:45-51.
Mewis C, Kühlkamp V, Mermi J, Bosch RF, Seipel L. Long-term
reproducibility of electrophysiologically guided therapy with sotalol
in patients with ventricular tachyarrhythmias. J Am Coll Cardiol
;33(7):1989-95.
Rao KS, Fernando JC, Ho IK, Mehendale HM. Neurotoxicity in rats
following subchronic amiodarone treatment. Res Commun Chem
Pathol Pharmacol 1986;52(2):217-24.
Candinas R, Frielingsdorf J, Ha HR, Carrel T, Turina M, Follath F.
Myocardial amiodarone concentrations after short- and long-term
treatment in patients with end-stage heart failure. Eur J Clin Pharmacol
;53:331-6.
Shoyinka SV, Obidike IR, Ndumnego CO. Effect of iodine
supplementation on thyroid and testicular morphology and function in
euthyroid rats. Vet Res Commun 2008;32(8):635-45.
Kronenberg, Melmed S, Polonsky K, Larsen PR. Regulation of CRH.
In: Williams’s Textbook of Endocrinology. 12th ed.
Philadelphia: Elsevier; 2011. p.
Newton GL, Barrick ER, Harvey RW, Wise MB. Iodine toxicity.
Physiological effects of elevated dietary iodine on calves. J Anim Sci
;38(2):449-55.
Dussarat GV, Dalger J, Chaix AF. Pheochromocytoma and
hyperthyroidism caused by amiodarone. Ann Cardiol Angeiol (Paris)
;37(4):195-7.
Morales AI, Barata JD, Bruges M, Arévalo MA, González de
Buitrago JM, Palma P, et al. Acute renal toxic effect of amiodarone in
rats. Pharmacol Toxicol 2003;92(1):39-42.
Dobs AS, Sarma PS, Guarnieri T, Griffith L. Testicular dysfunction
with amiodarone use. J Am Coll Cardiol 1991;18(5):1328-32.
Peltola V, Mantyla E, Huhtaniemi I, Ahotupa M. Lipid peroxidation
and antioxidant enzyme activities in the rat testis after cigarette
smoke inhalation or administration of polychlorinated biphenyls or
polychlorinated napthalenes. J Androl 1994;15(4):353-61.
Walsh LP, McCormick C, Martin C, Stocco DM. Roundup inhibits
steroidogenesis by disrupting steroidogenic acute regulatory (StAR)
protein expression. Environ Health Perspect 2000;108(8):769-76.
Pellegrini A, Grieco M, Materazzi G, Gesi M, Ricciardi MP.
Stress-induced morphohistochemical and functional changes in
rat adrenal cortex, testis and major salivary glands. Histochem J
;30(10):695-701.
Vereckei A, Blazovics A, Gyorgy I, Feher E, Toth M, Szenasi G, et al.
The role of free radicals in the pathogenesis of amiodarone toxicity.
J Cardiovasc Electrophysiol 1993;4(2):161-77.
Gutowski M, Kowalczyk S. A study of free radical chemistry: Their role
and pathophysiological significance. Acta Biochim Pol 2013;60(1):1-16.
Joanta AE, Filip A, Clichici S, Andrei S, Daicoviciu D. Iodide excess
exerts oxidative stress in some target tissues of the thyroid hormones.
Acta Physiol Hung 2006;93(4):347-59.
Ghosh D, Firdaus SB, Mitra E, Dey M, Bandyopadhyay D. Protective
effect of aqueous leaf extract of Murraya koenigi against lead inducedoxidative stress in rat liver, heart and kidney: A dose response study.
Asian J Pharm Clin Res 2012;5(4):54-8.
Bellen JC, Penglis S, Tsopelas C. Radiolabeling and biodistribution
of amiodarone and desethylamiodarone. Nucl Med Biol
;22(7):953-5.
Simon JB, Manley PN, Brien JF, Armstrong PW. Amiodarone
hepatotoxicity simulating alcoholic liver disease. N Engl J Med
;311(3):167-72.
Dzobo K, Naik YS. Effect of selenium on cadmium-induced oxidative
stress and esterase activity in rat organs. S Afr J Sci 2013;109:1-8.
Chiovato L, Martino E, Tonacchera M, Santini F, Lapi P, Mammoli C,
et al. Studies on the in vitro cytotoxic effect of amiodarone.
Endocrinology 1994;134(5):2277-82.
Pitsiavas V, Smerdely P, Li M, Boyages SC. Amiodarone induces
a different pattern of ultrastructural change in the thyroid to iodine
excess alone in both the BB/W rat and the Wistar rat. Eur J Endocrinol
;137(1):89-98.
Bartalena L, Grasso L, Brogioni S, Aghini-Lombardi F, Braverman LE,
Martino E. Serum interleukin-6 in amiodarone-induced thyrotoxicosis.
J Clin Endocrinol Metab 1994;78(2):423-7.
Dunn JT. What’s happening to our iodine? J Clin Endocrinol Metab
;83(10):3398-400.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.