Blood Plasma as a Sampling Model during Drug-induced Thrombocytopenia: Effects of Antioxidants
Keywords:
antioxidants, caripill, L-carnitine, oxidative stress, plasma, thrombocytopenia, vanillic acidAbstract
OBJECTIVE Blood plasma, a complex biological mixture, plays a part in a variety of roles including clotting, defense, and transport, and reflects the overall status of blood components. Drug-induced thrombocytopenia (DIT) is characterized by abnormally low platelet count (below ~150,000 per μL) which can be caused by adverse effects of medications. This study aims to address a basic question, can plasma be employed as a sampling model to assess the oxidative stress (OS) changes and antioxidant status during DIT? The objective was to analyze the antioxidant status and OS in plasma during DIT, and to determine the effects of antioxidant supplementation such as Caripill™, L-Carnitine (LC), and vanillic acid (VA) during DIT.
METHODS Male Wistar rats were used as animal models and grouped into control groups (n=5) and thrombocytopenia groups (n=5). Antioxidants were given to the thrombocytopenic and the control rats (50 mg/kg body weight) once a day for 7 days. Blood plasma from both groups was evaluated for total antioxidant capacity, antioxidant enzymes, markers of lipid peroxidation, protein oxidation, and OS.
RESULTS The antioxidants significantly increased the total antioxidant capacity (CUPRAC) and ferric-reducing antioxidant power (FRAP) of the plasma and decreased the levels of conjugate dienes. Caripill™ also reduced lipid peroxidation, significantly elevated protein sulfhydryl and nitrite/nitrate levels, LC elevated lactate dehydrogenase levels, and VA increased superoxide dismutase activity and attenuated lipid peroxidation during DIT.
CONCLUSIONS The antioxidants Caripill™, vanillic acid, and L-carnitine were demonstrated to be beneficial during DIT and to have prospects in alternate therapeutics. This study confirms that plasma can be utilized as a sampling model to study changes during OS situations.
References
Anderson S, Lightfoot D. Principles of physiology. Cambridge: Cambridge University Press, 2002. p. 704.
Tortora G. Principles of anatomy and physiology. 10th Edition. New Jersey: John Wiley & Sons; 2003.
Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 1997;82:291-5.
Schiller H, Reily P, Bulkley G. Antioxidant therapy. J Crit Care Med. 1993;21:92-102.
Chakraborty P, Kumar S, Dutta D, Gupta V. Role of antioxidants in common health diseases. Res J Pharm Technol. 2009;2:238-244.
Greenberg E, Kaled E. Thrombocytopenia. Crit Care Nurs Clin North Am, 2013;25:427-34.
Chong B, Choi P, Khachigian L. Drug-induced immune thrombocytopenia. Hematol Oncol Clin North
Am. 2013;27:521-40.
De Silva E, Hugh K. Drug-induced thrombocytopenia: Focus on platelet apoptosis. Chem Biol Interact.
;284:1-11.
George J, Raskob G, Shah S, Rizvi M, Hamilton S, Osborne S. Drug-Induced Thrombocytopenia: A Systematic Review of Published Case Reports. Ann InternMed. 1998;129:886-90.
Saeed F, Arshad M, Pasha I, Naz R, Batool R, Khan A, Nasir M, Shafique B. Nutritional and phyto-therapeutic
potential of papaya (Carica papaya Linn.): an overview. Int J Food Prop. 2014;17:1637-53.
Gammulle A, Ratnasooriya W, Jayakody Fernando C, Chamini K, Preethi V. Thrombocytosis and anti-inflammatory properties, and toxicological evaluation of Carica papaya mature leaf concentrate in a murine model. Online Int J Med Plant Res. 2012;1:21-30.
Yudisthira D, Firdausi F, Alyani C, Nurkolis F, Al Rasyid H, Yusuf V, Taslim N. Potential of Carica papaya leaf extract as an future medicine for thrombocytopenia in dengue patients: from traditional to scientific drug discovery. Adv Tradit Med. 2023:1-4.
Chou T, Ding H, Hung W, Liang C. Antioxidative characteristics and inhibition of α‐melanocyte‐stimulating hormone‐stimulated melanogenesis of vanillin and vanillic acid from Origanum vulgare. Exp Dermatol. 2010;19:742-50.
Salau V, Erukainure O, Ibeji C, Olasehinde T, Koorbanally N, Islam M. Vanillin and vanillic acid modulate antioxidant defense system via amelioration of metabolic complications linked to Fe2+-induced brain tissues damage. Metab Brain Dis. 2020;35:727-38.
Shabani M, Jamali Z, Bayrami D, Salimi A. Vanillic acidalleviates methamphetamine-induced mitochondrial toxicity in cardiac mitochondria via antioxidant activity and inhibition of MPT Pore opening: an in-vitro study. BMC Pharmacol Toxicol. 2023;24:33. PubMed PMID: 37208773
Gülçin I. Antioxidant and antiradical activities of L-carnitine. Life Sci. 2006;78:803-11.
Ravikumar S, Prabhu S, Vani R. Effects of L‐carnitine on the erythrocytes of stored human blood. Transfusion Medicine. 2020;30:215-25.
Caballero-García A, Noriega-González D, Roche E, Drobnic F, Córdova A. Effects of L-carnitine intake
on exercise-induced muscle damage and oxidative stress: a narrative scoping review. Nutrients. 2023;15:
PubMed PMID: 37299549
Devi S, Subramanyam M, Vani R, Jeevaratnam K. Adaptations of the antioxidant system in erythrocytes of trained adult rats: impact of intermittent hypobaric-hypoxia at two altitudes. Comp Biochem Physiol C Toxicol Pharmacol. 2005;140:59-67.
Dodge J, Mitchell C, Hanahan DJ. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963;100:119-30.
Misra H, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247:3170-5.
Aebi H. Catalase in vitro. Meth Enzymol. 1984;105:121-6.
Da Cruz G. US Patent for use of bathocuproine for the evaluation of the antioxidant power in liquids and solutions. US patent. 6613577. 2003.
Olas B, Nowak P, Kolodziejczyk J, Ponczek M, Wachowicz B. Protective effects of resveratrol against
oxidative/nitrative modifications of plasma proteins and lipids exposed to peroxynitrite. J Nutr Biochem.
;17:96-102.
Olas B, Wachowicz B. Resveratrol and vitamin C as antioxidants in blood platelets. Thromb Res. 2002;106:143-8.
Reznick A, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Meth Enzymol. 1994;233:357-63.
Habeeb AFSA. Reaction of Protein Sulfhydryl Groups with Ellman’s Reagent. Meth Enzymol. 1972;25:457-64.
Benzie I, Strain J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239:70-6.
Chen L, Mehta P, Mehta J. Oxidized LDL decreases L-arginine uptake and nitric oxide synthase protein
expression in human platelets. Circulation. 1996;93:1740-6.
Yegin S, Yur F, Çetin S, Güder A. Effect of lycopene on serum nitrite-nitrate levels in diabetic rats. Indian J Pharm Sci. 2015;77:357-60.
Buhl S, Jackson K. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30 and 37°C. Clin Chem. 1978;24:828-31.
Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with the Folin phenol reagent. J Biol
Chem. 1951;193:265-75.
Matés J, Pérez-Gómez C, De Castro I. Antioxidant enzymes and human diseases. Clin Biochem. 1999;32:595-603.
Kumar S, Prahalathan P, Raja B. Antihypertensive and antioxidant potential of vanillic acid, a phenolic
compound in L-NAME-induced hypertensive rats: a dose-dependence study. Redox Rep. 2011;16:208-15.
Augustyniak A, Bartosz G, Cipak A, Duburs G, Horáková L, Luczaj W, et al. Natural and synthetic antioxidants:an updated overview. Free Rad Res. 2010;44:1216-62.
Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging. 2007;2:219-36.
Campos C, Guzmán, R, López-Fernández E, Casado A. Evaluation of the copper(II) reduction assay using bathocuproinedisulfonic acid disodium salt for the total antioxidant capacity assessment: the CUPRAC-BCS assay. Anal Biochem. 2009;392:37-44.
Ognik K. Effect of L-carnitine on the level of biochemical and antioxidant indices of blood of Turkey
hens. Ann UMCS Zootechnica. 2012;30:1-10
Son S, Lewis B. Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues: Structure-activity relationship. J Agri Food Chem. 2002;50:468-72.
Schiller H, Reilly P, Bulkley G. Antioxidant therapy. Crit Care Med. 1993;21:S92-102.
Janero D. Malondialdehyde and thiobarbituric acid- reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med. 1990;9:515-40.
Stadtman E, Levine R. Free radical-mediated oxidation of free amino acids and amino acid residues in
proteins. Amino Acids. 2003;25:207-18.
Molicki J, Draaisma A, Verbeet N, Munneke R, Huysmans H, Hazekamp M, Berger H. Prime solutions for cardiopulmonary bypass in neonates: Antioxidantcapacity of prime based on albumin or fresh frozen
plasma. J Thorac Cardiovasc Surg. 2001;122:449-56.
Omparn P, Hisalaphong C, Akornchai S, Nichern S, Orales N. Comparative antioxidant activities of curcumin and its dimethoxy and hydrogenated derivatives. Biol Pharm Bull. 2007;30:74-8.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and (15N) nitrate in biological fluids. Anal Biochem.1982;126:131-8.
Bloodsworth A, O’ Donnell VB, Freeman BA. Nitric oxide regulation of free radical- and enzyme-mediated lipid and lipoprotein oxidation. Arterioscler Thromb Vasc Biol. 2000;20:1707-15.
Klein R, Nagy O, Tóthová C, Chovanová F. Clinical and diagnostic significance of lactate dehydrogenase and its isoenzymes in animals. Vet Med Int. 2020;2020: 5346483. PubMed PMID:32607139
