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Current Drug Discovery Technologies


ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Research Article

In Vitro Protective Effect of Ascorbic Acid Against Antibiotic-Induced Hepatotoxicity

Author(s): Veneta Simon, Sreerag K.V., R. Sasikumar and S.K. Kanthlal*

Volume 17, Issue 3, 2020

Page: [357 - 364] Pages: 8

DOI: 10.2174/1570163816666190204122007

Price: $65


Background: Although antibiotic-induced hepatotoxicity is recoverable with mild impairment, and some cases were reported to cause morbidity. However, an adjuvant is essential in reducing such incidences.

Objective: The aim of this study is to evaluate the protective effect of ascorbic acid on antibiotic induced liver toxicity using liver slices.

Method: Fresh liver slices were incubated with different concentrations of sulfamethoxazole tetracycline and clavulanic acid along with ascorbic acid (200μg/ml) for 2 hours. The liver homogenate was assessed for markers like ALT, AST, MDA and CAT levels. Cytotoxicity assessment was performed using MTT assay.

Results: Incubating liver slices with all three antibiotics shows elevated levels of aminotransferases, MDA and CAT enzyme when compared to the control groups which indicates the level of hepatotoxicity. In the presence of ascorbic acid, the elevated levels of TBARS, ALT and AST were significantly reduced which showcases the protective effect of ascorbic acid. The percentage survival of cell was also shown to have improved while accessed using cell viability assay.

Conclusion: Obtained data suggests that consuming vitamin C or vitamin C containing food like citrus fruits or green leafy vegetables equivalent to 3g/day during antibiotic treatment, perhaps put down the risk of liver toxicity to a greater extent.

Keywords: Liver toxicity, ascorbic acid, antibiotics, antioxidants, antibiotic-induced hepatotoxicity.

Graphical Abstract
Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: A review. J Appl Pharm Sci 2012; 2: 233-43.
Granitznya A, Knebela J, Schaudiena D, et al. Maintenance of high quality rat precision cut liver slices during culture to study hepatotoxic responses: Acetaminophen as a model compound. Toxicol In Vitro 2012; 42: 200-13.
Mishra S, Aeri V, Katare DP. Hepatoprotective Medication for Liver Injury. World J Pharm Pharm Sci 2014; 3: 891-32.
Luo G, Shen Y, Yang L, Lu A, Xiang Z. A review of drug-induced liver injury databases. Arch Toxicol 2017; 91(9): 3039-49.
[] [PMID: 28717830]
Laxminarayan R, Chaudhury RR. Antibiotic Resistance in India: Drivers and Opportunities for Action. PLoS Med 2016; 13(3)e1001974
[] [PMID: 26934098]
Andrade RJ, Tulkens PM. Hepatic safety of antibiotics used in primary care. J Antimicrob Chemother 2011; 66(7): 1431-46.
[] [PMID: 21586591]
Andrade RJ, López-Ortega S, López-Vega MC, Robles M, Cueto I, Lucena MI. Idiosyncratic drug hepatotoxicity: a 2008 update. Expert Rev Clin Pharmacol 2008; 1(2): 261-76.
[] [PMID: 24422651]
Thiim M, Friedman LS. Hepatotoxicity of antibiotics and antifungalsClin Liver Dis 2003; 7(2) 381-399, vi-vii.
[] [PMID: 12879990]
Andrade RJ, Lucena MI, Fernández MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129(2): 512-21.
[] [PMID: 16083708]
Singh D, Cho WC, Upadhyay G. Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview. Front Physiol 2016; 6: 363.
[] [PMID: 26858648]
Kuppusamy A, Muthuswamy U, Abdulkadar B, Andichettiyar TS, Varadharajan S, Thengungal KR. Antioxidant and Hepatoprotective activities of the fractions of Ficus microcarpa using in-vitro and ex-vivo models. Funct Plant Sci Biotechnol 2010; 4: 17-27.
Verma N, Behera BC, Makhija U. Antioxidant and hepatoprotective activity of a lichen Usnea ghattensis in vitro. Appl Biochem Biotechnol 2008; 151(2-3): 167-81.
[] [PMID: 18975145]
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[PMID: 14907713]
Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP. Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress. J Pharm Pharm Sci 2004; 7(2): 274-83.
[PMID: 15367386]
Hadwan MH. New Method for Assessment of Serum Catalase Activity. Indian J Sci Technol 2106(9): 1-5.
Faedmaleki F, H Shirazi F, Salarian AA, Ahmadi Ashtiani H, Rastegar H. Toxicity Effect of Silver Nanoparticles on Mice Liver Primary Cell Culture and HepG2 Cell Line. Iran J Pharm Res 2014; 13(1): 235-42.
[PMID: 24734076]
Simmons C. Beware: antibiotic-induced hepatotoxicity is rare but deadly. Hosp Pharm 2002; 37: 326-30.
Sugimoto T, Nobuhara Y, Kawano S, Morinobu A. Trimethoprim-Sulfamethoxazole-Induced Hepatitis in Mixed Connective Tissue Disease. Int J Clin Med 2011; 2: 629-32.
Björnsson E, Lindberg J, Olsson R. Liver reactions to oral low-dose tetracyclines. Scand J Gastroenterol 1997; 32(4): 390-5.
[] [PMID: 9140164]
Glenn C, Feldman SR. Letter: Tetracycline-induced hepatotoxicity. Dermatol Online J 2011; 17(12): 14.
[PMID: 22233750]
García Rodríguez LA, Stricker BH, Zimmerman HJ. Risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid. Arch Intern Med 1996; 156(12): 1327-32.
[] [PMID: 8651842]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[] [PMID: 11089981]
Apel K, Hirt H. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 2004; 55: 373-99.
[] [PMID: 15377225]
Li S, Tan HY, Wang N, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci 2015; 16(11): 26087-124.
[] [PMID: 26540040]
Ramasamy P, Subhapradha N, Shanmugam V, Shanmugam A. Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury. Int J Biol Macromol 2014; 65: 559-63.
[] [PMID: 24530330]
Stine JG, Chalasani N. Chronic liver injury induced by drugs: a systematic review. Liver Int 2015; 35(11): 2343-53.
[] [PMID: 26346512]
Shuhendler AJ, Pu K, Cui L, Uetrecht JP, Rao J. Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing. Nat Biotechnol 2014; 32(4): 373-80.
[] [PMID: 24658645]
Ramanathan K, Balakumar BS, Panneerselvam C. Effects of ascorbic acid and alpha-tocopherol on arsenic-induced oxidative stress. Hum Exp Toxicol 2002; 21(12): 675-80.
[] [PMID: 12540038]
Patra RC, Swarup D, Dwivedi SK. Antioxidant effects of α tocopherol, ascorbic acid and L-methionine on lead induced oxidative stress to the liver, kidney and brain in rats. Toxicology 2001; 162(2): 81-8.
[] [PMID: 11337108]
Gruss-Fischer T, Fabian I. Protection by ascorbic acid from denaturation and release of cytochrome c, alteration of mitochondrial membrane potential and activation of multiple caspases induced by H(2)O(2), in human leukemia cells. Biochem Pharmacol 2002; 63(7): 1325-35.
[] [PMID: 11960609]
Lima TB, Suja A, Jisa OS, Sathyanarayanan S, Remya KS. Hepatoprotective activity of LIV-first against carbon tetra chloride-induced hepatotoxicity in albino rats. Int J Green Pharm 2010; 4: 71-4.
Nagalekshmi R, Menon A, Chandrasekharan DK, Nair CK. Hepatoprotective activity of Andrographis paniculata and Swertia chirayita. Food Chem Toxicol 2011; 49(12): 3367-73.
[] [PMID: 21983487]
Das SK, Vasudevan DM. Biochemical diagnosis of alcoholism. Indian J Clin Biochem 2005; 20(1): 35-42.
[] [PMID: 23105491]
Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ 2005; 172(3): 367-79.
[] [PMID: 15684121]
MacDonald GA, Bridle KR, Ward PJ, et al. Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3. J Gastroenterol Hepatol 2001; 16(6): 599-606.
[] [PMID: 11422610]
Murugesh KS, Yeligar VC, Maiti BC, Maity TK. Hepatoprotective and antioxidant role of Berberis tinctoria Lesch leaves on paracetamol induced hepatic damage in rats. Iranian J Pharmcol Ther 2005; 4: 64-9.
Simon V, Sreerag KV, Sasikumar R, Kanthlal SK. High dose antibiotics induced hepatotoxicity and altered markers: An in vitro liver slices study. Res J Pharm Tech 2017; 10: 1742-5.
Kirkman HN, Rolfo M, Ferraris AM, Gaetani GF. Mechanisms of protection of catalase by NADPH. Kinetics and stoichiometry. J Biol Chem 1999; 274(20): 13908-14.
[] [PMID: 10318800]
Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in disease prevention and cure: an overview. Indian J Clin Biochem 2013; 28(4): 314-28.
[] [PMID: 24426232]

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