Ameliorative effects of vitamins C and E on tenofovir/nevirapine-induced hepatorenal oxidative stress in albino rats

Elias Adikwu, Williams Apiakise

Abstract


Background and Objectives: Oxidative stress has been implicated in xenobiotic-induced hepatorenal toxicity. This research was designed to investigate the effects of vitamins C and E on the baseline and tenofovir/nevirapine-induced liver and kidney levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) in male albino rats. Materials and Methods: Forty five male albino rats were used for this study. The rats were divided into groups A – I of 5 rats each.   Group A (placebo control) and group B (solvent control) were orally treated with water and arachis oil respectively.  Groups C – F were orally treated with vitamins C, E, vitamins C and E, and tenofovir/nevirapine respectively. Groups G– I were pretreated with vitamins C, E and vitamins C and E prior to treatment with tenofovir/nevirapine respectively. Rats were sacrificed after treatment for 30 days; liver and kidneys were collected and evaluated for the above parameters. Results: Significant (p<0.05) increases in the baseline levels of liver and kidney SOD, GSH, and CAT with decreases in MDA levels were obtained in vitamins C and E treated rats when compared to control. On the contrary, treatment with tenofovir/nevirapine significantly (p<0.05) decreased liver and kidney SOD, GSH, and CAT levels with increases in MDA levels when compared to control. However, all tenofovir/nevirapine -induced alterations were abrogated in rats pretreated vitamins C and E. Abrogation was most pronounced in rats pretreated with combined doses of vitamins C and E. Conclusion: Observations in the present study could be attributed to the inhibitory effects of vitamins C and E on the oxidative activity of tenofovir/nevirapine in the liver and kidney of treated rats.


Keywords


tenofovir; nevirapine; liver; kidney; oxidative stress; antioxidants; rats

Full Text:

PDF

References


Abraham P, Kolli VK and Rabi S Melatonin attenuates methotrexate-induced oxidative stress and renal damage in rats, Cell Biochemistry and Function, 2010; 28; 5; 426–433

Adaramoye OA Adewumi OM, Adesanoye OA, Faokule OO, Farombi EO. Effect of tenofovir, an antiretroviral drug, on hepatic and renal functional indices of Wistar rats: protective role of vitamin E,” Journal of Basic and Clinical Phys and Pharma 2012; 23; 2; 69–75,

Adaramoye OA, Adesanoye OA, Adewumi OM, and Akanni O,Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats,” Human and Experimental. Toxicology, 2013; 13; 676-685,

Adikwu E and N. Brambaifa, 2013.Concentration-effect, incidence and mechanism of nevirapine hepatotoxicity,” American Journal of Pharmacology and Toxicology, vol. 8 no. 1, pp. 20-30,

Adikwu E, Oputiri D, Oru-Bo P and Akuegbe ED Nevirapine hepatotoxicity: implications of risk factors,” American Journal of Pharmacology and Toxicology; 2013; 8 ; 2; 51-63,

Adikwu E, Onyedenyifa JO, and Bibowei AA. Remedial Effects of Vitamins C and E on Atazanavir/Ritonavir-Induced Alterations in Biomarkers of Renal Function and Oxidative Stress indices of Male Int Jour of Biomed Res;2006; 7;4; 1993-2000

Adikwu E, Onyedenyifa OJ, and Newman K. S. Beneficial Effects of Vitamins C and E on Tenofovir and Nevirapine-Induced hepatorenal toxicity in male albino rats International Journal of Biomedical Research 2016; 7(4): 205-212

An Y, Xin H, Yan W, Zhou X . Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice,”Experimental and Toxicological Pathology, 2009; 63: 215-219

Anderson ME.. Glutathione: an overview of biosynthesis and modulation, Chemico- Biological Interactions, 1998; 111; 2:1–14

Arias, IM, Jakoby WB , Popper H, Scachter D, Schafritz DA, Section 4 the organ: The hepatic microvascular system. The liver: Biology and Pathobiology, 3rd Ed. Lippincott Williams & Wilkins, 1997. Available from: URL:

Avery, SV. Molecular targets of oxidative stress,” Biochemical Journal, 2011; 434; 2; 201–210

Aziz FM, Maulood I, Chawsheen MAH. Effects of melatonin, vitamin C and E alone or in combination on lead-induced injury in liver and kidney organs of rats IOSR Journal of Pharmacy, 2012; 2; 5; 13-18

Babiak EM, Campello AP, Carnieri EGS, Oliveira MB.. Methotrexate, pentose cycle and oxidative stress,” Cell Biochemistry and Function,1998; 283; 93,

Books, McGraw Hill Company, 2003: 332-343

Bowler C, M. Montagu Y, and Irize D. Superoxide Dismutase and stress toleranceAnnual Review of Plant Physiology and Plant Molecular Biology, 1992;43; 83-116

British National Formulary 37, March, 1999

Buege, J.A. and S.D. Aust.. Microsomal lipid peroxidation methods. Enzymol.,1978; 52: 302-310

Carr AC, and Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans,” American Journal of Clinical Nutrition, 1999; 69; 6; 1086-1107

Chu KM, Boulle AM, Ford N, Goemaere E, Asselman V, and Van Cutsem G, “Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care art programme in South Africa,” PLoS ONE, 2010; 5, (2), Article ID e9183,.

Combs J and F. Gerald. The vitamins. 4 ed. Burlington: Elsevier Science; 2012

Deavall DG, Martin EA, Horner JM, and Roberts R. Drug-Induced Oxidative Stress and Toxicity Journal of Toxicology Volume 2012 , Article ID 645460, page.13

El-hadjela, D,K. Zine, and B. Leila, The beneficial effect of combined administration of vitamins C and E on renal function and selected parameters of antioxidant system in diabetic rats fed zinc-deficient diet,”African Journal of Biotechnology, 2003; 12; 43; 6232-6240,

Fridovich I “Superoxide radical and superoxide dismutases,” Annual Review of Biochemistry, 1995; 64; 97-112,

Gallant JE, and Deresinski S .Tenofovir disoproxil fumarate, Clinical Infectious Disease.,2003; 37: 944-950,

Hammer SM, Eron JJ, Reiss P, et al., .Antiretroviral treatment of adult HIV infection: 2008 recommendations of the international AIDS society USA panel Journal of American Medical Association, 2008; 300, 555–70,

Herrera, C. and. Barbas Vitamin E: action, metabolism and perspectives Journal of Physiology and Biochemistry, 2001; 57; 2; 43-56

Johnson F, and C. Giulivi, . Superoxide dismutases and their impact upon human health,” Molecular Aspects Medicine, 2005; 26; 340–352

Johnson VA, Brun-Ve´zinet F, Clotet B, Conway B,D’Aquila RT, Demeter LM. Update of the drugresistance mutations in HIV-1. Topics HIV Med.;2004; 12: 119–124

Junqueira LC, Carneiro J; Basic Histology Text & Atlas. 10thEdition, New York: Lange Medical

Kanter M, Aksu, B , Akpolat, M , Tarladacalisir, YT, Aktas C, , Uysal H,Vitamin E Protects against Oxidative Damage Caused by Cadmium in the Blood of Rats,”European Journal of General Medicine, 2009; 6; 3, 154-160,

Layachi N and Kechrid Z. Combined protective effect of vitamins C and E on cadmium induced oxidative liver injury in rats, African Journal of Biotechnology, 2012;11(93), 16013-160.

Li TS, Tubiana R, Katlama C, Calvez V, Ait Mohand H, Autran B. Long-lasting recovery in CD4 T-cell function andviral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease” Lancet, 1998 351; 1682–6

Martínez E, J. L. Blanco, J. A. Arnaiz et al., “Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy,” AIDS, 2001; 15; 10; 1261–1268.

Mullineaux,P, and Creissen GP (1997) Glutathione reductase: regulation and role in oxidative stress Oxidative stress and the molecular biology of antioxidant defenses. Cold Spring Harbor Laboratory Press;

Packer L, Weber SU, Rimbach G . Molecular aspects of alphatocotrienol antioxidant action and cell signaling,” Journal of Nutrition, 2001; 131; 2;369–373

Packer, L and Fuchs J , “Vitamin C in health and disease” Marcel Dekker, Inc., New York, Basel, Hong Kong (1997).

RaghavendraM. J, instrumentation and control engineering functions of kidney & artificial kidneys, Intern Jour of Innov Res in Elec, Elec,; 2013; 1 (1) :1-5

Ramamoorthy H, Abraham P and Isaac B, “Preclinical efficacy of melatonin in the amelioration of tenofovir nephrotoxicity by the attenuation of oxidative stress, nitrosative stress and inflammation in rats,” Journal of Basic Clin Physio and Pharm, 2014; 25: 4: 387–399,

Ramamoorthy H, Abraham P, Isaac, B. Oxidative stress, decreased activities of anti-oxidant enzymes, and neutrophil infiltration contribute to Tenofovir disoproxil fumarate induced renal damage in rats, ”International Research of Pharmacy and Pharmacology; 2012; 1; 10; 259-270

Sadi G, Eryilmaz N, Tütüncüoğlu E,. Cingir S, Güray T. Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys Diabetes/Metabolism Research and Review, 2012; 28, ; 3; 228-235,

Sánchez DJ . Effects of exposure to BDE-99 on oxidative status of liver and kidney in adult rats,” Toxicology, 2010; 271; 51-6

Saravanan R, Rajendra N, Prasad NR, and Pugalendi KV . Effect of Piper betle leaf extract on alcohol toxicity in the rat brain. Journal of Medicinal Food, 2013 6; 3; 261-265

Sasse D, Spronitz UM, Mally IP,. Liver architectureEnzyme, 2013; 1992:46: 8-32

Sedlak, J. and Lindsay RH.. Estimation of total, protein-bound and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem. 1968; 25: 192-205.

Sert C, Elük MS, Akdaú Z, Ketanü MA, , Nergüz Y, “Radioprotective Effect of Vitamins C, E and Vitamin E + Glutathione on the Small Intestine and the Thyroid Gland in Rats Irradiated with XRays,”Turkey Journal of Medical Science, 2000; 30; 417-425,

Sies H, “Oxidative Stress: Introductory Remarks. In: Oxidative Stress,” Academic Press, London, 1985,

Sinha, A.K, . Colorimetric Assay of catalase. Anal. Biochem. 1972; 47. 2: 389-394.

Sohini S V, Rana S . Protective effect of ascorbic acid against oxidative stress induced by inorganic arsenic in liver and kidney of rat Indian Journal of Experiment Biology, 2007; 45; 371-375

Sun, M. And Zigma, S.,. An improved spectrophotometer assay of superoxide dismutase based on Epinephrine Antioxidation. Analytical Biochemistry. 1978; 90: 81-89

Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more.Free Rad. Biol. Med. 2007 43: p. 4

Uboh F E, Ebong PE, Akpan HD, Usoh IT. Hepatoprotective effect of vitamins C and E against gasoline vapor-induced liver injury in male rats, Turk J Biol 2012; 36 ; 217-223

Wirtz KW.. Molecular mechanisms of signaling and membrane transport. Proceedings of the NATO study institute on molecular mechanism of signaling targeting. Island of Spetsai, Greece August 18-30, 1996

Woodward CL, Hall AM, Williams IG , et al, .Tenofovir associated renal and bone toxicity. Human immunodeficiency Medicine, 2009 : 10 :482-487

Yin Y, Xu L, and Porter NA . Free radical lipid peroxidation: mechanisms and analysis,” Chemical Reviews, 2011; 111; 10; 5944–5972.




DOI: http://dx.doi.org/10.14499/indonesianjpharm27iss4pp211

Refbacks

  • There are currently no refbacks.




Copyright (c) 2017 INDONESIAN JOURNAL OF PHARMACY

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:

                                               

web
analytics View My Stats