Abstract
Background and Objectives
Apigenin is known to have various pharmacological properties without causing significant toxicity; however, hepatoprotective effect of apigenin is not often reported. The aim of our study was to investigate if the alterations in lipid peroxidation and antioxidant status are in favor to prove the efficacy of apigenin against paracetamol-induced hepatotoxicity.
Methods
The effect of apigenin on paracetamol-induced hepatotoxicity in rats was examined by determining biochemical parameters, histological assessment and oxidative status in liver homogenates.
Results
The treatment of animals with both apigenin and paracetamol attenuates the parameters of hepatotoxicity, especially for ALT and ALP activity which was significantly lower compared to groups of animals treated with saline and paracetamol. Hepatotoxicity induced by toxic dose of paracetamol was revealed also by notable histopathological alterations, which were not observed in the group treated with paracetamol together with apigenin. Apigenin also prevented paracetamol-induced increase in malondialdehyde (MDA) level. The activities of both CAT (catalase) and GR (glutathione reductase) enzymes after the toxic dose of paracetamol were significantly increased in the liver homogenates, compared to control group. Apigenin reversed these parameters near to values of control group.
Conclusions
The result of our study indicates that apigenin inhibits the level of lipid peroxidation and significantly increases the enzyme antioxidant defense mechanisms in paracetamol-induced hepatotoxicity in rats.
Similar content being viewed by others
References
Bhakuni GS, Bedi O, Bariwal J, Deshmukh R, Kumar P. Animal models of hepatotoxicity. Inflamm Res. 2016;65:13–24.
Gu X, Manautou JE. Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med. 2012;14:e4. doi:10.1017/S1462399411002110.
Corsini A, Bortolini M. Drug-induced liver injury: the role of drug metabolism and transport. J Clin Pharmacol. 2013;53:463–74.
Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, Sumaya-Martínez MT, Gutiérrez-Salinas J, Bautista M, Morales-González Á, García-Luna y González-Rubio M, Aguilar-Faisal JL, Morales-González JA. Review of natural products with hepatoprotective effects. World J Gastroenterol. 2014;20:14787–804.
Rašković A, Milanović I, Pavlović N, Ćebović T, Vukmirović S, Mikov M. Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential. BMC CAM. 2014;14:1.
Rašković A, Pavlović N, Kvrgić M, Sudji J, Mitić G, Čapo I, Mikov M. Effects of pharmaceutical formulations containing thyme on carbon tetrachloride-induced liver injury in rats. BMC CAM. 2015;15:1.
Zhang A, Sun H, Wang X. Recent advances in natural products from plants for treatment of liver diseases. Eur J Med Chem. 2013;63:570–7.
Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. Sci World J. 2013. doi:10.1155/2013/162750.
Lefort ÉC, Blay J. Apigenin and its impact on gastrointestinal cancers. Mol Nutr Food Res. 2013;57(1):126–44.
Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27:962–78.
Yang J, Wang XY, Xue J, Gu ZL, **e ML. Protective effect of apigenin om mouse acute liver injury induced by acetaminophen is associated with increment of hepatic glutathione reductase activity. Food Funct. 2013;4:939–43.
Tsaroucha AK, Tsiaousidou A, Ouyounidis N, Tsalkidou E, Lambropoulou M, Giakoustidis D, et al. Intraperitoneal administration od apigenin in liver ischemia/reperfusion injury protective effects. Saudi J Gastroenterol. 2016;22(6):415–22.
Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–10.
Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952;195:133–40.
Beutler E. Red cell metabolism: a manual of biochemical methods. New York: Grune & Stratton Inc; 1984.
Goldberg D, Spooner R. Glutathione reductase. Methods Enzym Anal. 1983;3:258–65.
Ajiboye T. Standardized extract of Vitex doniana Sweet stalls protein oxidation, lipid peroxidation and DNA fragmention in acetaminophen-induced hepatotoxicity. J Ethnopharmacol. 2015;164:273–82.
Pápay ZE, Antal I. Study on the antioxidant activity during the formulation of biological active ingredient. ESJ. 2014;3:252–7.
Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: a review. J Appl Pharm Sci. 2012;2:233–43.
Kleinman J, Breitenfield R, Roth D. Acute renal failure associated with acetaminophen ingestion: report of a case and review of the literature. Clin Nephrol. 1980;14:201–5.
Nelson SD, Bruschi SA. Mechanisms of acetaminophen-induced liver disease. In: Kaplowitz N, De Leve LD, editors. Drug-induced liver disease. New York: Marcel Dekker; 2002. p. 287–325.
Ilavenil S, Al-Dhabi NA, Srigopalram S, Ock Kim Y, Agastian P, Baru R, Choi KC, Valan Arasu M. Acetaminophen induced hepatotoxicity in wistar rats—a proteomic approach. Molecules. 2016;21:161.
Ali F, Naz F, Jyoti S, Siddique YH. Protective effect of apigenin against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in albino rats. Mutat Res, Genet Toxicol Environ Mutagen. 2014;767:13–20.
Ahlenstiel T, Burkhardt G, Köhler H, Kuhlmann MK. Bioflavonoids attenuate renal proximal tubular cell injury during cold preservation in Euro-Collins and University of Wisconsin solutions. Kidney Int. 2003;63:554–63.
Chakravarthi S, Haleagrahara N, Wen CF, Lee N, Thani P. C-myc regulation and apoptosis in assessing the beneficial effect of apigenin in cyclosporine induced nephrotoxicity. Res J Pharmacol. 2010;4:15–20.
Chakravarthi S, Chiang LL, Nagaraja HS. Histopathological study and immunohistochemical expression of TGF-β in the role of 4′,5′,7′ trihydroxyflavone in acute renal failure. J Clin Exp Pathol. 2012;2:5.
Esterbauer H, Schaur R Jr, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1990;11:81–128.
Singh JPV, Selvendiran K, Banu SM, Padmavathi R, Sakthisekaran D. Protective role of Apigenin on the status of lipid peroxidation and antioxidant defense against hepatocarcinogenesis in Wistar albino rats. Phytomedicine. 2004;11:309–14.
Mora A, Paya M, Rios J, Alcaraz M. Structure-activity relationships of polymethoxyflavones and other flavonoids as inhibitors of non-enzymic lipid peroxidation. Biochem Pharmacol. 1990;40:793–7.
Cholbi M, Paya M, Alcaraz M. Inhibitory effects of phenolic compounds on CCl4-induced microsomal lipid peroxidation. Experientia. 1991;47:195–9.
Seifried HE, Anderson DE, Fisher EI, Milner JA. A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem. 2007;18:567–79.
Zhu R, Wang Y, Zhang L, Guo Q. Oxidative stress and liver disease. Hepatol Res. 2012;42:741–9.
Halliwell B, Gutteridge J. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J. 1984;219:1.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Author Aleksandar Rašković, Author Slobodan Gigov, Author Ivan Čapo, Author Milica Paut Kusturica, Author Boris Milijašević, Author Sunčica Kojić-Damjanov, and Author Nikola Martić declare that they have no conflict of interest.
Funding
This work was supported by Provincial Secretariat for Higher Education and Scientific Research (Project No. 142-451-3680/2016-03) and by the Ministry of Science and Technological Development, Republic of Serbia (Project No. 41012).
Ethical Approval
Animal care and all experimental procedures were performed in agreement with the UK Animals Act 1986 and associated guidelines, the EEC Directive of 1986 (86/609/EEC). This study was approved by the Ethical Committee of the University of Novi Sad (Approval No. 01-160/9).
Rights and permissions
About this article
Cite this article
Rašković, A., Gigov, S., Čapo, I. et al. Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model. Eur J Drug Metab Pharmacokinet 42, 849–856 (2017). https://doi.org/10.1007/s13318-017-0407-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13318-017-0407-0