Ascorbic acid attenuates ethanol induced apoptotic and oxidative response by blocking the Bax, Bcl2 and Caspase signaling pathways
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20220413Keywords:
Apoptosis, Ascorbic acid, Antioxidant, Caspase, Ethanol, Oxidative stressAbstract
Background: Research evidence has demonstrated that oxidative stress plays important etiological role in pathogenesis of alcoholic liver disease. The agents having antioxidant property plays a promising therapeutic intervention in ALD. In our present study we investigate the effect of ascorbic acid on ethanol induced liver injury and molecular mechanism of ethanol induced apoptosis.
Methods: Wistar albino rats were randomly divided into 4 groups with 6 animals in each group control, ethanol treatment 40% (2ml/100gm), ethanol+ascorbic acid 100mg/kg b.w. intra-gastric gavage, ethanol+silymarin 100mg/kg b.w. intra-gastric gavage for 21 days. Statistical analysis was carried out using one-way ANOVA followed by Tukey multiple comparision test.
Results: Ethanol induced hepatotoxicity is evidenced by increased level of liver marker enzymes (AST, ALT, ALP and LDH) and lipid peroxidation whereas the level of antioxidants (SOD, CAT, GSH, VIT C and E) was significantly decreased. Our results are further supported by histopathological examination which shows drastic changes in liver architecture. Hepatic Bax, Bcl-2, Caspase 3 and Caspase 9 proteins expressions were altered. On contrary treatment with ascorbic acid ameliorated the changes induced by ethanol and improved liver architecture.
Conclusions: Ascorbic acid as an antioxidant protect the liver from ethanol induced oxidative damage and apoptosis.
References
Pal P, Ray S. Alcoholic liver disease: a comprehensive review. EMJ 2016;1(2):85-92.
Kapasi AA, Patel G, Goenka A. Ethanol promotes T cell apoptosis through the mitochondrial pathway. Immunology. 2003;108:313-20.
Wu D, Cederbaum AI. Alcohol, oxidative stress and free radical damage. Alcohol Res Health. 2003;27: 277-84.
Koch OR, Pani G, Borrello S, Colavitti R, Cravero A, Farre S, et al. Oxidative stress and antioxidant defenses in ethanol-induced cell injury. Mol Asp Med. 2004;25:191-8.
Stangeland T, Remberg, SF, Lye KA. Total antioxidant activity in 35 Ugandanfruits and vegetables. Food Chem. 2008;113:85-91.
Xavier SM, Barbosa CO, Barros DO, Silva RF, Oliveria AA, Freitas RM. Vitamin C antioxidant in hippocampus of adult Wistar rats after seizures andstatus epilepticus induced by pilocarpine. Neurosci Lett. 2007;420:76-9.
Adikwu E, Deo O. Hepatoprotective effect of vitamin C (ascorbic acid). Pharmacol Pharmacy. 2013;4:84-92.
Tarasankar M, Ayaz A, Pahari N. Evaluation of hepatotherapeutic effects of Mikania Scandens (L.) Willd. On alcohol induced hepatotoxicity in rats. Int J Pharm Pharm Sci. 2012;4(3):490-4.
Basini J, Mohanalakshmi S, Anitha k. Protective effect of Mirabilis jalapa leaves on Anti-tubercular drugs induced hepatotoxicity. Asian J Pharm Clin Res. 2013;6:221- 24.
Ibrahim MA, Buhari GO, Aliyu AB. Amelioration of Monosodium Glutamate- Induced Hepatotoxicity by Vitamin C. Eur J Sci Res. 2011;60:159-65.
Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxide in animal tissue by TBA reaction. Anal Biochem. 1979;95:351-8.
Kakkar P, Das B and Viswanathan PN. A modified spectrophotometric assay of SOD. Indian J Biochem Biophys. 1984; 21:130-2.
Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389-94.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium, Biochemical role as a component of glutathione peroxidase. Science. 1973;179:588-90.
Omaye ST, Turnbull JD, Sauberlich, HE. Selected methods for the determination of ascorbic acid in animal cells, tissues and fluids. Methods Enzymol. 1979;62:1-11.
Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol. 1984;105:138-44.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin’s phenol reagent. J Biol Chem. 1951;193:265-75.
Zakhari S, Li TK. Determinants of alcohol use and abuse: Impact of quantity and frequency patterns on liver disease. Hepatology. 2007;46:2032-9.
Zima T, Fialova L, Mestek O, Janebova M, Crkovska J, Malbohan I, et al. Oxidative stress, metabolism of ethanol and alcohol-related diseases. J Biomed Sci. 2001;8:59-70.
Soo-Jung L, Seon-Young K, Hyesun M. Effects of vitamin C and E supplementation on oxidative stress and liver toxicity in rats fed a low-fat ethanol diet. Nutr Res Pract. 2013;7(2):109-14.
Das SK, Mukherjee S, Gupta G, Rao DN, Vasudevan DM. Protective effect of resveratrol and Vitamin E against ethanol –induced oxidative damage in mice: Biochemical and immunological basis. Indian J Biochem Biophysics. 2010;47:32-7.
Tuma DJ, Thiele GM, Xu D, Klassen LW, Sorrell MF. Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration. Hepatology. 1996;23:872-80.
Leelavinothan P, Asaithambi K, Paramasivam K, Ayyasamy R. Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats. Toxicol Rep. 2015;2:46-55.
Elias A, Oputiri D. Hepatoprotective effect of vitamin C (Ascorbic Acid). Pharmacol Pharmacy. 2013;4:84-92.
Bendich A. In: Bendich A, Chandra, RK, eds. Micro-nutrients and Immune Functions. New York: Academy Sciences; 1990:175.
Haorah J, Ramirez SH, Floreani N, Gorantla S, Morsey B, Persidsky Y. Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radic Biol Med. 2008;45:1542-50.
Uwe W, Alexander N, Sabine K, Hannelore D. Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions. Carcinogenesis. 2004;25,703-12.
Alhusaini AM, Faddah LM, Hasan IH. Vitamin C and turmeric attenuate Bax and Bcl-2 proteins' expressions and dna damage in lead acetate-induced liver injury. Dose Response. 2019;17:155.