Abstract
Background:
A constellation of reactive oxygen species (ROS) capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. The consequences of this leads to enhanced oxidative stress and lower antioxidant status. Enzymatic antioxidants provide first line defense against ROS. We have measured the levels of oxidative stress indices like lipid peroxidation (LPO), protein carbonyls together with enzymatic antioxidants in the blood samples of control and leprosy patients. Nutritional rehabilitation by way of exogenous supplementation of functionally efficient antioxidants like vitamin E reactivates the enzymatic antioxidant system and guards against the insult caused by ROS during the pathogenesis of the disease and antileprosy chemotherapy.
Design:
Untreated leprosy patients were selected on the basis of clinical examination and skin smear. All diagnosed untreated leprosy patients received multi drug therapy (MDT) consisting of rifampicin, dapsone and clofazimine as recommended by World Health Organization. A small number of untreated cases were selected for co-supplementation of vitamin E along with MDT. Oxidative stress indices, enzymatic and nonenzymatic antioxidant status were assayed in untreated, MDT treated and those supplemented vitamin E along with MDT.
Statistical methods:
We have compared the significance in the meanĀ±s.d. values of the oxidative stress indices and the levels of antioxidants using one way analysis of variance (ANOVA) between control, untreated, MDT treated and those supplemented vitamin E with MDT and the results were significant at P<0.05. Statistical analysis of the results suggests that oral administration of vitamin E lowers oxidative stress and augments antioxidant status in affected individuals.
Results:
Enhanced oxidative stress as evidenced by increased LPO and protein carbonyl in leprosy cases lowers the antioxidant status. Treatment with MDT has a limited impact on increased oxidative stress and decreased antioxidant status. Coadministration of vitamin E along with MDT decreases oxidative stress and activate the antioxidant status.
Discussion:
The excess production of ROS as seen in leprosy cases could lead to degeneration of tissues and derangement of internal organs. The possible reason for the decreased antioxidant status in leprosy cases may be increased production of ROS, deranged liver function, and the free radical producing ability of drugs used in MDT of leprosy. Intervention with antioxidant supplementation like vitamin E prevents oxidative stress mediated through ROS and activates the net antioxidant status during the chronic course of the disease and antileprosy chemotherapy.
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References
Agnihotri N, Ganguly NK, Kaur S, Khullur M, Sharma SC & Chugh KS (1995): Role of reactive oxygen species in renal damage in experimental leprosy. Leprosy Rev. 66, 201ā209.
Aviram I & Shaklai H (1981): The association of human erythrocyte catalase with cell membrane. Arch. Biochem. Biophys. 212, 329ā337.
Baker H & Frank O (1968): Assay of vitamin E in plasma. Clin Vitaminology. New York: Wiley, 172.
Behl C (1999): Vitamin E and other antioxidants in neuroprotection. Int. J. Vitamin Nutr. Res. 69, 213ā219.
Bergel M (1998): Leprosy as a Metabolic Disease (Book), Institute of Leprological Research.
Berlett BS & Stadtman ER (1997): Protein oxidation in ageing, disease and oxidative stress. J. Biol. Chem. 272, 20313ā20316.
Bray T & Tailor GK (1993): Tissue glutathione, nutrition and oxidative stress. Can. J. Physiol. Pharmacol. 71, 746ā751.
Brito T, Carvalho N, Marques AC, Penna DO & Azevedo MP (1969): The liver in lepromatous leprosy. A Bio-chemical, functional and ultrastructural study. Int. J. leprosy 37, 154ā163.
Cemerski S, Cantagrel A, van Meerwijk JPM & Ramagnoli P (2002): Reactive oxygen species differently affect T cell receptor-signaling pathways. J. Biol. Chem. 277, 19585ā19593.
Chandra RK (1992): Effect of vitamin and trace element supplementation on immune responses and infection in elderly subjects. Lancet 340, 1124ā1127.
Dean RT, Shalin FU, Stocker R & Davis MJ (1997): Biochemistry and pathology of radical-mediated protein oxidation. Biochem. J. 262, 9895ā9901.
Dodge JT, Carolyn M & Donald JH (1963): Preparation and chemical characteristics of hemoglobin free ghost of human erythrocytes. Arch. Biochem. Biophys. 100, 199ā230.
Flohe BR & Traber MG (1999): Vitamin E: Function and metabolism. FASEB J. 13, 1145ā1150.
Frankel EN & Neff WE (1985): Formation of malondialdehyde from lipid oxidation products. Biochem. Biophys. Acta. 754, 264ā270.
Freeman BA & Crapo JD (1982): Free radical and tissue injury. J. Lab. Invest. 47, 412ā426.
Gerson RJ & Shaikh ZA (1984): Differences in the āuptake of cadmium and mercury by the rat hepatocyte primary cultureārole of sulfhydryl carrier. Biochem. Pharmacol. 33, 199ā203.
Grosset JH (1989): Study of 39 documented relapses at multibacillary leprosy cases after treatment with rifampicin. Int. J. leprosy 58, 281ā295.
Habig WH, Pabste MJ & Jakoby WB (1974): Glutathione-S-transferease: the first enzymatic step in mercaputuric acid formation. J. Biol. Chem. 249, 7130ā7139.
Halliwel B & Gutteridge J (1985): Oxygen radicals and the nervous system. Trends Neurosci. 8, 22ā26.
Hiramatsu K, Rosen H, Heinecke JW, Wolfbauer G & Chait A (1987): Superoxide initiates oxidation of low-density lipoprotein by human monocytes. Artherosclerosis 7, 55ā60.
Jallow DJ, Timothy B & MecMillan DC (1995): Dapsone induced hemolytic anemia. Drug. Metabolism Rev. 27, 107ā127.
Job CK, Yoder L, Jacobson RR & Hastings RC (1990): Skin pigmentation from clofazimine therapy in leprosy patients a reappraisal. J. Am. Acad. Dermatol. 23, 236ā241.
Jobling WH (1983): Side effects of antileprosy drugs in common use. Lep. Rev. 54, 261ā270.
Kalaiselvi K, Rajaguru P, Palanivel M, Usharani MV & Ramu G (2002): Chromosomal aberration, micronucles and comet assays on peripheral blood lymphocytes of leprosy patients undergoing multidrug treatment. Mutagenesis 17, 309ā312.
Katoch VM (2002): Recent developments in the diagnosis of leprosy, Expert reviews in molecular medicine. Cambridge: Cambridge University Press.
Lachant NA & Tanaka KR. (1987): Dapsone-associated heinz body hemolytic anemia in a Cambodian women with hemoglobin E trait. Am. J. Med. Sci. 294, 364ā368.
Lardo MM, Diaz NB, Artaza JR, Carbia CD, Nazer R & Valdez R (1997): Vitamin E as protective agent against hemolysis in leprosy patients under dapsone treatment. Medicina 57, 150ā154.
Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shariel S & Stadtman ER (1990): Deter mination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 186, 464ā478.
Lockwood DNJ (2002): Leprosy eliminationāa virtual phenomenon or a reality? BMJ 22, 1516ā1518.
Maydani SM (1995): Fat soluble vitaminsāvitamin E. Lancet 345, 170ā175.
Maydani SM, Barlund MP, Liu S, Miller RA, Cannon JG, Morrow FD, Rocklin R & Blumberg JB (1990): Vitamin E supplementation enhances cell mediated immunity in healthy elderly subjects. Am. J. Clin. Nutr. 52, 557ā563.
McCay PB (1985): Vitamin E: interactions with free radicals and ascorbate. Ann. Rev. Nutr. 5, 323ā340.
McDougall AC & Jones RL (1981): Intra-neural ceroid pigment following the treatment of lepromatous leprosy with clofazimine (Lamprene). J. Neurol. Neurosurg. Psychiatr. 44 (2), 116ā120.
MecRury SM, Gorden D, Wilson R, Bradley H, Gemmel CG, Patterson JR, Rumally AG & Maccuish AC (1993): A comparison of different methods of assaying free radical activity in type II diabetes and peripheral vascular disease. Diab. Med. 10, 331ā335.
Misra HP & Fridovich IP (1972): The role of superoxide dismutase (SOD) in the auto oxidation of epinephrine and a simple assay for SOD. J. Biol. Chem. 243, 3170ā3175.
Moron MS, Depierre JW & Mannervik B (1979): Levels of glutathione, glutathione reductase and glutathione S transferase in rat lung and liver. Biochem. Biophys. Acta. 582, 67ā70.
Niki E (1987): Interaction of ascorbate and alpha tocopheroal. Ann. NY. Acad. Sci 498, 186ā189.
Niki E, Naguchi N, Tsuchihashi H & Gotoh N (1995): Interaction among vitamin C, vitamin E and Ī²-carotene. Am. J. Clin. Nutr. 62, 1322sā1326s.
Omaye ST, Turnbull JD & Suberlich HE (1979): Selected methods for determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol. 62, 1ā11.
Packer JE, Slater TF & Wilson RL (1979): Direct observation of a free radical interacation between vitamin E and vitamin C. Nature 278, 737ā738.
Poli G (1993): Liver damage due to free radicals. British Med. Bull. 49, 604ā620.
Quist EM (1980): Regulation of erythrocyte membrane shape by calcium. Biochem. Biophys. Res. Commun. 92, 631ā637.
Rao DN & Cederbaum AI (1997): A comparitive study on redox cycling of a quinone (rifampicin S) and Quinomine (rifambutin) antibiotic by rat liver microsomes. Free Rad. Biol. Med. 22 (3), 439ā446.
Ridley DS & Jobling WB (1966): Classification of leprosy according to immunity. A five group system. Int. J. Leprosy 34, 255ā273.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG & Hoekstra HG (1973): Selenium: Biochemical role as a component of glutathione peroxidase. Science 179, 558ā590.
Safarian MD, Karangezian KG, Karapetian ET & Avenesian NA (1990): The efficacy of antioxidant therapy in patients with tuberculosis of lungs and the correction of lipid peroxidation process. Probl. Tuberk 5, 40ā44.
Sheppard AJ, Pennington JAT & Weihracuch JL (1983): Analysis and distribution of vitamin E in vegetable oils and food. In: L Packer & J Fuchs, (eds) Vitamin E in Health and Diseases. New York: Marcel Deckkar Inc., 9ā13.
Sheriff DS (1989): Erythrocyte glutathione concentration as a measure of oxidant stress in patients undergoing dapsone therapy. Ann. Clin. Biochem. 26, 199ā200.
Sies H (1993): Strategies of antioxidant defense. Eur. J. Biochem. 215, 213ā219.
Sinha AK (1972): Colorimetric assay of catalase. Anal. Biochem. 47, 389ā394.
Staal GEJ, Visser J & Veeger C (1969): Purification and properties of glutathione reductase of human erythrocytes. Biochem. Biophys. Acta. 185, 39ā48.
Timothy PB, Mc Millan DC, Crouch RK & Jollow DJ (1997): Formation of Free radicals and protein mixed disulfides in rat red cell exposed to dapsone hydroxylamine. Free Radic. Biol. Med. 27 (7), 1183ā1193.
Urano S, Inomori Y & Sugawara T (1992): Vitamin E inhibition of retinol induced hemolysis and membrane stabilizing behaviour. J. Biol. Chem. 267, 18365ā18370.
Van Acker SABE, Koyamans LMH & Bast A (1993): Molecular pharmacology of vitamin E: Structural aspects of antioxidant activity. Free Radic. Biol. Med. 15, 311ā328.
Walsh DS, Lane JE, Abalos RM & Myint KS (2004): TUNEL and limited immuno phenotypic analysis of apoptosis in paucibacillary and multibacillary leprosy lesions. FEMS Immunol. Med. Microbiol. 41, 265ā269.
WHO (World Health Organization) study group (1982): Chemotherapy of leprosy, world health organization. Technical report series. Geneva: WHO. p 675.
Winker BS (1992): Unequivocal evidence in support of the non-enzymatic redox coupling between glutathione/glutatione disulfide/ascorbic acid/and dehydroascorbic acid. Biochem. Biophys. Acta. 1117, 287ā290.
World health organization (2002): Report on third meeting of the WHO technical advisory group on the elimination of leprosy. Geneva: WHO. p 29.
Yagi K. (1982) In: Lipid peroxides in Biology and medicine. New York: Academic Press, 223ā242.
Yu PB (1994): Cellular defense against damage from reactive oxygen species. Physiol. Rev. 74, 134ā162.
Acknowledgements
We acknowledge the valuable suggestions of Dr K Prabhakaran, Senior Scientist, Biochemistry Research Branch, Gillis W Long Hansen's Disease Center at Louisiana State University, Baton Rouge. USA We are also thankful to the former Directors of CLT & RI, Dr VN Bhatia, Dr KV Krishnamurthy, Dr LN Rao Bhau and clinicians Dr E Jeyarama, Dr S Thangaiah, Dr V Durai, Dr PK Panda, Dr S Sathiya, Dr TS Geetha for their support and help in diagnosis and classification, and the laboratory staff of CLT & RI : Mr M Rajendren, Mr TK Ramaswamy, Mr D Anandan. Mr K Arunagiri of CLT & RI for their technical assistance. We are thankful to the librarian of CLT & RI Mr A Rajendran and Mr V Sundaraj for providing relevant literature. The study subjects receive our thanks for their cooperation. We are grateful to Soft caps India Limited, Chennai (Madras), for providing vitamin E capsules.
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Guarantor: R Vijayaraghavan and C Panneerselvam.
Contributors: CP is a professor of medical biochemistry mainly responsible for ideas, design and guidance of this study. CSS is a biochemist with prolonged experience in the field of Biochemical aspects of Hansen's disease (Leprosy) coordinated in the sampling in this study. BS and PKO are experts in the field of Hansen's disease (leprosy) who served as advisors and examined the diagnostic aspects of this study. SNK and NM are research scientists who contributed to the statistical analysis of this manuscript and interpretation of results.
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Vijayaraghavan, R., Suribabu, C., Sekar, B. et al. Protective role of vitamin E on the oxidative stress in Hansen's disease (Leprosy) patients. Eur J Clin Nutr 59, 1121ā1128 (2005). https://doi.org/10.1038/sj.ejcn.1602221
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DOI: https://doi.org/10.1038/sj.ejcn.1602221
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