The Effects of Amoxicillin Clavulanic Acid, Amoxicillin Clavulanic Acid + Vitamin Administration on Malondialdehyde and Antioxidant Levels in Kidney and Liver Tissues of the Rats

Year 2017, Volume: 10 Issue: 3, 180 - 186, 01.03.2017

Emine Altın , Ali Ertekin

Abstract

It is aimed to investigate the effects of Amoxicillin Clavulanic Acid (AKA) and vitamins on antioxidants and oxidative stress in liver and kidney tissues of the rats. 49 Wistar-albino male rats were divided into seven groups. We applied; group1: AKA, group2: AKA+vitamin C, group3: AKA+vitamin E, group4: AKA+vitamin C+vitamin E, group5: vitamin C, group6: vitamin E and group7: as a control group. At the end of the study Malondialdehyde(MDA), reduced glutathione(GSH), catalase activities(CAT), vitaminC, total protein levels in liver and kidney tissues of the rats were analyzed, and plasma ALT, AST and GGT levels were measured. The ALT increased significantly in Group1(p<0.001). Renal tissue MDA increased in only group1(p<0.05). A significant decrease was determined in GSH levels in group2 and 4(p<0,05). CAT showed a significant increase in group1(p<0.01) and a decrease in group4(p<0.05). Group6 showed an increase in CAT activity(p<0.01). Renal tissue vitaminC was significantly lower in group1(p<0.001). Liver tissue MDA were increased in all groups(1., 3. and 5. groups p<0.05; 2., 4. and 6. groups p<0.01). GSH decreased in only group4(p<0.01). CAT activities decreased significantly in all other groups (group1 and 2; p<0.01, group6; p<0.05). VitaminC decreased in group1(p<0.001) and group2(p<0.01) significantly. Total protein in liver tissue decreased only in group4(p<0.001). Changes in parameters suggest that there may be oxidative damage-induced degenerations in liver and kidney cells. As a result, it has come to the conclusion that it may be useful to use antioxidants in addition to antibiotics against oxidative damage.

Keywords

Amoxicillin clavulanic acid, Antioxidants, Malondialdehyde, Rat, Vitamin

Amoksisilin Klavulanik Asit, Amoksisilin Klavulanik Asit+Vitamin Uygulamasının Ratların Böbrek ve Karaciğer Dokularındaki Malondialdehit ve Antioksidan Düzeylerine Etkisi

Abstract

Bu çalışmayla amoksisilin klavulanik asitin (AKA) ve vitaminlerin, sıçanların karaciğer ve böbrek dokusunda antioksidanlar ve oksidatif stres üzerine etkilerini incelemek amaçlandı. 49 Wistar–albino erkek sıçan; 1. grup: AKA, 2. grup: AKA+vitamin C, 3. grup: AKA+vitamin E, 4. grup: AKA+vitamin C+vitamin E, 5. grup: vitamin C, 6. grup: vitamin E, 7. grup: kontrol grubu olarak ayrıldı. Çalışma sonunda karaciğer ve böbrek dokusunda malondialdehit (MDA), redükte glutatyon (GSH), katalaz aktivitesi (CAT), vitamin C, total protein, plazma ALT, AST ve GGT miktarları ölçüldü. 1. grupta ALT önemli düzeyde arttı (p<0.001). Böbrek dokusu MDA sadece 1. grupta artış gösterdi (p<0.05). Böbrek dokusu GSH düzeylerinde 2. ve 4. grupta önemli miktarda azalma saptanmıştır (p<0.05). Böbrek dokusu CAT aktivitesi 1. grupta önemli bir artış (p<0.01), 4. grupta ise azalma gösterdi (p<0.01). 6. grupta CAT aktivitesinde artış gözlendi (p<0.05). Böbrek dokusu vitamin C 1. grupta önemli derecede düşük bulundu (p<0.001). Karaciğer dokusu MDA grupların tamamında artış göstermiştir ( 1., 3. ve 5. grup, p<0.05; 2., 4. ve 6. grup, p<0.01). GSH sadece 4. grupta azaldı (p<0.01). CAT aktiviteleri diğer bütün gruplarda önemli düzeyde azaldı (1. 2. grupta (p<0.01), 6. grupta(p<0.05). VitaminC 1.(p<0.001) ve 2. grupta (p<0.01) önemli derecede azalmıştır. Total protein karaciğer dokusunda sadece 4. Grupta (p<0.001) azalmıştır. Parametrelerdeki değişimler karaciğer ve böbrek hücrelerinde oksidatif hasardan kaynaklı dejenerasyonların olabileceğini göstermektedir. Sonuç olarak, oksidatif hasarlara karşı antibiyotiğe ek olarak antioksidanların da kullanılmasının faydalı olabileceği kanısına varılmıştır. 

Keywords

Amoksisilin klavulanik asit, Antioksidanlar, Malondialdehit, Sıçan, Vitamin

References

• Acharya C, Thakar H, Vajpeyeel SK. A study of oxidative stress in gentamicin induced nephrotoxicity and effect of antioxidant vitamin C in Wistar rats. Natl J Physiol Pharm Pharmacol. 2013; 3(1):14–20.
• Aebi H. Catalase in vitro. Enzymol. 1984; 105:121-6.
• Akkuş İ. Serbest Radikaller ve Fizyopatolojik Etkileri. Birinci Baskı, Konya: Mimoza Yayınları 1995; 50-120.
• Barja G, Lopez-Torres M, Perez-Campo R, Rojas C, Cadenas S, Prat J, Pamplona R. Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. Free Radic Biol Med. 1994; 17: 105–15.
• Brunton LL, Lazo JS, Parker KL. Goodman & Gilman Tedavinin Farmakolojik Temeli, Çev. Ed: Süzer Ö, İstanbul; Nobel Tıp Kitabevleri, 2009; 1133-52.
• Cadenas S, Lertsiri S, Otsuka M, Barja G, Miyazawa T. Phospholipid hydroperoxides and lipid peroxidation in liver and plasma of ODS rats supplemented with alpha tocopherol and ascorbic acid. Free Radic Res. 1996; 24: 485–93.
• Crossman G.A. Modification of Mallory's connective tissue stain with a discussion of the principles involved, The Anatomical Record. 1937; 69(1): 33-8.
• Daş A. Enzootik pneumoni besi kuzularında tedaviye selenyum vevitamin E eklenmesinin total oksidan ile antioksidan seviyeleri üzerine etkilerinin araştırılması. Yüksek Lisans Tezi, Harran Üniversitesi Sağlık Bilimleri Enstitüsü, Şanlıurfa 2009; p. 30-9.
• Djordjeviš BV,Šosiš V, Pavloviš D, Vlahoviš P, Jevtoviš T, Kociš G, Saviš V. Does captopril change oxidative stress in puromycin aminonucleoside nepropathy? Renal Fail. 2000; 22: 535-44.
• Durmuş AS, Ünsaldı E. Serbest oksijen radikalleri, antioksidanlar ve kırık iyileşmesi. Doğu Anadolu Bölgesi Araştırmaları 2005; 20-7.
• Dwyera DJ, Belenkya PA, Yanga JH, MacDonalda IC, Martelld JD, Takahashie N, Chana CTY, Lobritza MA, Braff D, Schwarza EG, Yea JD, Patih M, Vercruyssee M, Ralifoh PS, Allisoni KR, Khalilb AS, Tingd AY, Walkere GC, Collinsa JJ. Antibiotics induce redox-related physiological alterations as part of their lethalit. PNAS. 2014; 6: 2100-9.
• El-Sherbiny GA, Ashraf Taye A, Abdel-Raheem IT. Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats. Ann Hepatol 2009; 8(2):134-40.
• Gönenç S. Egzersiz ve oksidan stres. BESBD. 1997; 2(4): 26-38.
• Granowitz EV, Brown RB. Antibiotic adverse reactions and drug ınteractions. Crit Care Clin. 2008; 24: 421–42.
• 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(4): 571–6.
• Kaya S. Veteriner Farmokoloji. Dördüncü Baskı, Ankara: Medisan Yayınları 2007; 361-8.
• Keren I, Wu Y, Inocencio J, Mulcahy LR, Lewis K. Killing by bactericidal antibiotics does not depend on reactive oxygen species. Science. 2013; 339 (6124): 1213-6.
• Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA,Collins JJ. A common mechanism of cellular death induced by bactericidal antibiotics. Cell. 2007; 130:797–810.
• Lucena MI, Andrade RJ, Fernández MC, Pachkoria K, Pelaez G, Duran JA, Villar M, Rodrigo L, Romero-Gomez M, Planas R, Barriocanal A, Costa J, Guarner C, Blanco S, Navarro JM, Pons F, Castiella A. Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain. Hepatology. 2006; 44: 850-6.
• Macfarlane I, Bomford A, Sherwood RA. Liver Diseases and Laboratory Medicine. London: ACB Venture Publications 2000; 357-60.
• Olayinka ET, Olukowade IL. Effect of amoxycillin/clavulanic acid (Augmentin 625®) on antioxidant indices and markers of renal and hepaticdamage in rats. J Toxicol Environ Health Sci. 2010; 2(6): 85-92.
• Omaye ST, Turbul JD, Savberlich HE. Ascorbic acid analyses. II. Determination after derivation with 2,2 dinitrophenylhidrazine, selected methods for determination of ascorbic acid in animal cell, tissues and fluids. Methods in Enzymology. 1979; 62: 7-8.
• Öncü S. Antibiyotiklerin istenmeyen etkilerinin izlemi-yönetimi. ANKEM Derg 2013;27: 82-4.
• Paolini M, Pozzetti L, Pedulli GF, Marchesi E, Cantelli-Forti G. The nature of prooxidant activity of vitamin C. Life Sci. 1999; 64: 273–8.
• Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O, Motola D, Dusi G, Caputi AP. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother. 2007; 60: 121– 6.
• Sezikli M, Çetinkaya ZA, Güzelbulut F, Yeşil A, S. Coşgun S, Kurdaş OÖ. Supplementing Vitamins C and E to standard triple therapy for the eradication of Helicobacter pylori. JCPT. 2012; 37: 282-5.
• Shinde A, Ganu J, Naik P. Effect of free radicals & antioxidants on oxidative stress: A Review. J Dent Allied Sci. 2012;1(2):63-6.
• Sushil JK, Mcvie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes. 1989; 38: 1539-43.
• Tabakoğlu E, Durgut R. Veteriner hekimlikte oksidatif stres ve bazı önemli hastalıklarda oksidatif stresin etkileri. AVKAE Derg. 2013; 3(1): 69-75.
• Tanaka K, Hashimoto T, Tokumaru S, Iguchi H, Kojo S. Interactions between vitamin C and vitamin E are observed in tissues of inherently scorbutic rats. J Nutr. 1997; 127: 2060–4.
• Tiftik AM. Biüret Metoduyla Total Protein Tayini, Klinik Biyokimya, Konya: Mimoza Yayınları 1996; sayfa: 291-2.
• Trevor AJ, Katzung BG, Kruidering-Hall M, Masters SB. Katzung & Trevor’s Pharmacology Examination & Board Review, Tenth Edition, New York: McGraw Hill Companies Inc 2013: p: 384-448.
• Tuzcu S. Tanıda Laboratuvar Testleri. Yedinci Baskı, İstanbul: Yüce Yayımları 2003; sayfa: 58-68.
• Ünal K, Palabıyık İM, Karacan E, Onur F. Spectrophotometric determination of amoxicillin in pharmaceutical formulations. Turk J Pharm Sci. 2008; 5(1): 1-16.
• Valko M, Jomova K, Rhodes CJ, Kuca K, Musílek K. Redox- and non‑redox‑metal‑induced formation of free radicals and their role in human disease. Arch Toxicol. 2016; 90:1–37.
• Valko M, Leibfritz D, Jan Moncol J, Cronin MTD, Mazur M, Tels J. Free radicals and antioxidants in normal physiological functions and human disease. IJBCB. 2007; 39: 44–84.
• Yüzüak H, Akbulut KG, Yüzüak S. Yaşlanma sürecinde melatoninin pankreas dokusundaki oksidan ve antioksidanlara etkisi. JCEI. 2014; 5(4): 583-8.