The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test (Lipid peroxidation), antioxidant parameter glutathione (GSH), and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250？mg/kg·bw) orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model. 1. Introduction Liver disease is one of the major health problems worldwide because liver is a vital organ has a wide range of functions in the body, including biotransformation and detoxification of endogenous and exogenous harmful substances, plasma protein synthesis, and glycogen storage [1]. Hepatic injury is associated with distortion of various metabolic functions. It is well known that reactive oxygen and nitrogen species play a crucial role in initiation and progression of liver-associated diseases such as alcoholic and viral hepatitis, nonalcoholic steatosis, and hepatocellular carcinoma [2–4]. The progression of liver fibrosis may develop into cirrhosis and is associated with liver cancer. Nearly 10–20% of patients’ progress to cirrhosis which further leads to increasing the risk of hepatocellular carcinoma [5]. Steroids, vaccines, and antiviral drugs have been employed for treatment of liver diseases which have adverse side effects if administrated for long term. Extensive studies reported that natural products with antioxidant activity are effective to prevent the oxidative stress-related liver pathologies due to particular interactions and synergisms [6]. Acetaminophen (paracetamol) is widely used as analgesic and antipyretic drug. Acetaminophen is primarily
References
[1]
M. Cemek, F. Aymelek, M. E. Büyükokuro？lu, T. Karaca, A. Büyükben, and F. Yilmaz, “Protective potential of Royal Jelly against carbon tetrachloride induced-toxicity and changes in the serum sialic acid levels,” Food and Chemical Toxicology, vol. 48, no. 10, pp. 2827–2832, 2010.
[2]
G. Hsiao, M.-Y. Shen, K.-H. Lin et al., “Antioxidative and hepatoprotective effects of Antrodia camphorata extract,” Journal of Agricultural and Food Chemistry, vol. 51, no. 11, pp. 3302–3308, 2003.
[3]
F. Morisco, P. Vitaglione, D. Amoruso, B. Russo, V. Fogliano, and N. Caporaso, “Foods and liver health,” Molecular Aspects of Medicine, vol. 29, no. 1-2, pp. 144–150, 2008.
[4]
K. Nagata, H. Suzuki, and S. Sakaguchi, “Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis,” Journal of Toxicological Sciences, vol. 32, no. 5, pp. 453–468, 2007.
[5]
J. Emerit, D. Samuel, and N. Pavio, “Cu-Zn super oxide dismutase as a potential antifibrotic drug for hepatitis C related fibrosis,” Biomedicine and Pharmacotherapy, vol. 60, no. 1, pp. 1–4, 2006.
[6]
P. Vitaglione, F. Morisco, N. Caporaso, and V. Fogliano, “Dietary antioxidant compounds and liver health,” Critical Reviews in Food Science and Nutrition, vol. 44, no. 7-8, pp. 575–586, 2004.
[7]
C. Cover, A. Mansouri, T. R. Knight et al., “Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity,” Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 2, pp. 879–887, 2005.
[8]
E. Bj？rnsson and R. Olsson, “Suspected drug-induced liver fatalities reported to the WHO database,” Digestive and Liver Disease, vol. 38, no. 1, pp. 33–38, 2006.
[9]
H. Jaeschke, T. R. Knight, and M. L. Bajt, “The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity,” Toxicology Letters, vol. 144, no. 3, pp. 279–288, 2003.
[10]
K. M. Sakthivel and C. Guruvayoorappan, “Biophytum sensitivum: ancient medicine and modern targets,” Journal of Advanced Pharmaceutical Technology & Research, vol. 3, no. 2, pp. 83–91, 2012.
[11]
Y.-L. Wu, D.-M. Piao, X.-H. Han, and J.-X. Nan, “Protective effects of salidroside against acetaminophen-induced toxicity in mice,” Biological and Pharmaceutical Bulletin, vol. 31, no. 8, pp. 1523–1529, 2008.
[12]
M. T. Olaleye, A. C. Akinmoladun, A. A. Ogunboye, and A. A. Akindahunsi, “Antioxidant activity and hepatoprotective property of leaf extracts of Boerhaavia diffusa Linn against acetaminophen-induced liver damage in rats,” Food and Chemical Toxicology, vol. 48, no. 8-9, pp. 2200–2205, 2010.
[13]
A. P. Firdous, E. R. Sindhu, and R. Kuttan, “Hepato-protective potential of carotenoid meso-zeaxanthin against paracetamol, CCl4 and ethanol induced toxicity,” Indian Journal of Experimental Biology, vol. 49, no. 1, pp. 44–49, 2011.
[14]
S. Fakurazi, S. A. Sharifudin, and P. Arulselvan, “Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature,” Molecules, vol. 17, no. 7, pp. 8334–8350, 2012.
[15]
M. I. Yousef, S. A. M. Omar, M. I. El-Guendi, and L. A. Abdelmegid, “Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat,” Food and Chemical Toxicology, vol. 48, no. 11, pp. 3246–3261, 2010.
[16]
J. H. Choi, C. Y. Choi, K. J. Lee, Y. P. Hwang, Y. C. Chung, and H. G. Jeong, “Hepatoprotective effects of an anthocyanin fraction from purple-fleshed sweet potato against acetaminophen-induced liver damage in mice,” Journal of Medicinal Food, vol. 12, no. 2, pp. 320–326, 2009.
[17]
T. Kalaivani and L. Mathew, “Free radical scavenging activity from leaves of Acacia nilotica (L.) Wild. ex Delile, an Indian medicinal tree,” Food and Chemical Toxicology, vol. 48, no. 1, pp. 298–305, 2010.
[18]
D. S. Seigler, “Phytochemistry of Acacia sensulato,” Biochemical Systematics and Ecology, vol. 31, no. 8, pp. 845–873, 2003.
[19]
S. K. Lam and T. B. Ng, “A dimeric high-molecular-weight chymotrypsin inhibitor with antitumor and HIV-1 reverse transcriptase inhibitory activities from seeds of Acacia confusa,” Phytomedicine, vol. 17, no. 8-9, pp. 621–625, 2010.
[20]
J. L. S. Lopes, N. F. Valadares, D. I. Moraes, J. C. Rosa, H. S. S. Araújo, and L. M. Beltramini, “Physico-chemical and antifungal properties of protease inhibitors from Acacia plumosa,” Phytochemistry, vol. 70, no. 7, pp. 871–879, 2009.
[21]
J.-C. Lee, W.-C. Chen, S.-F. Wu et al., “Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2,” Antiviral Research, vol. 89, no. 1, pp. 35–42, 2011.
[22]
S. Rajbir, S. Bikram, S. Sukhpreet, K. Neeraj, K. Subodh, and A. Saroj, “Umbelliferone—an antioxidant isolated from Acacia nilotica (L.) Willd. Ex. Del,” Food Chemistry, vol. 120, no. 3, pp. 825–830, 2010.
[23]
Y.-T. Tung, J.-H. Wu, C.-Y. Hsieh, P.-S. Chen, and S.-T. Chang, “Free radical-scavenging phytochemicals of hot water extracts of Acacia confusa leaves detected by an on-line screening method,” Food Chemistry, vol. 115, no. 3, pp. 1019–1024, 2009.
[24]
A. B. Dongmo, T. Nguelefack, and M. A. Lacaille-Dubois, “Antinociceptive and anti-inflammatory activities of Acacia pennata wild (Mimosaceae),” Journal of Ethnopharmacology, vol. 98, no. 1-2, pp. 201–206, 2005.
[25]
P. D. Meena, P. Kaushik, S. Shukla, A. K. Soni, M. Kumar, and A. Kumar, “Anticancer and antimutagenic properties of Acacia nilotica (Linn.) on 7,12-dimethylbenz(a)anthracene-induced skin papillomagenesis in Swiss albino mice,” Asian Pacific Journal of Cancer Prevention, vol. 7, no. 4, pp. 627–632, 2006.
[26]
H. A. Bachaya, Z. Iqbal, M. N. Khan, Z.-U. Sindhu, and A. Jabbar, “Anthelmintic activity of Ziziphus nummularia (bark) and Acacia nilotica (fruit) against Trichostrongylid nematodes of sheep,” Journal of Ethnopharmacology, vol. 123, no. 2, pp. 325–329, 2009.
[27]
I. M. S. Eldeen, F. R. Heerden, and J. Staden, “In vitro biological activities of niloticane, a new bioactive cassane diterpene from the bark of Acacia nilotica subsp. kraussiana,” Journal of Ethnopharmacology, vol. 128, no. 3, pp. 555–560, 2010.
[28]
R. Chaubal, A. M. Mujumdar, V. G. Puranik, V. H. Deshpande, and N. R. Deshpande, “Isolation and X-ray study of an anti-inflammatory active androstene steroid from Acacia nilotica,” Planta Medica, vol. 69, no. 3, pp. 287–288, 2003.
[29]
S. Sundarraj, R. Thangam, V. Sreevani et al., “γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells,” Journal of Ethnopharmacology, vol. 141, no. 3, pp. 803–809, 2012.
[30]
K. M. Sakthivel, N. Kannan, A. Angeline, and C. Guruvayoorappan, “Anticancer Activity of Acacia nilotica (L.) Wild. Ex. Delile Subsp. indica Against Dalton’s Ascitic Lymphoma Induced Solid and Ascitic Tumor Model,” Asian Pacific Journal of Cancer Prevention, vol. 13, no. 8, pp. 3989–3995, 2012.
[31]
P. T. Ramesh, “Evaluation of Liv.52 Vet drops in puppies,” Indian Veterinary Medical Journal, vol. 24, no. 1, pp. 157–158, 2000.
[32]
L. C. Miller and M. L. Tainter, “Estimation of LD50 and its error by means of log-probit graph paper,” Proceedings of the Society for Experimental Biology and Medicine, vol. 57, no. 3, p. 261, 1944.
[33]
P. D. Meena, P. Kaushik, S. Shukla, A. K. Soni, M. Kumar, and A. Kumar, “Anticancer and antimutagenic properties of Acacia nilotica (Linn.) on 7,12-dimethylbenz(a)anthracene-induced skin papillomagenesis in Swiss albino mice,” Asian Pacific Journal of Cancer Prevention, vol. 7, no. 4, pp. 627–632, 2006.
[34]
P. S. Ramya Krishna, L. Bhaduri, S. Pulla, S. Nagarjuna, and R. Y. Padmanabha, “Comparative study of Acacia nilotica and Acacia sinuata for diuretic activity,” Der Pharmacia Sinica, vol. 2, no. 6, pp. 17–22, 2011.
[35]
B. N. Singh, B. R. Singh, B. K. Sarma, and H. B. Singh, “Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark,” Chemico-Biological Interactions, vol. 181, no. 1, pp. 20–28, 2009.
[36]
O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” The Journal of Biological Chemistry, vol. 193, no. 1, pp. 265–275, 1951.
[37]
Q. Huang, S. Zhang, L. Zheng, M. He, R. Huang, and X. Lin, “Hepatoprotective effects of total saponins isolated from Taraphochlamys affinis against carbon tetrachloride induced liver injury in rats,” Food and Chemical Toxicology, vol. 50, no. 3-4, pp. 713–718, 2012.
[38]
H. Ohkawa, N. Ohishi, and K. Yagi, “Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction,” Analytical Biochemistry, vol. 95, no. 2, pp. 351–358, 1979.
[39]
G. Szasz, W. Gerhardt, W. Gruber, and E. Bernt, “Creatine kinase in serum: 2. Interference of adenylate kinase with the assay,” Clinical Chemistry, vol. 22, no. 11, pp. 1806–1811, 1976.
[40]
J. R. Mitchell, D. J. Jollow, and W. Z. Potter, “Acetaminophen induced hepatic necrosis. IV. Protective role of glutathione,” Journal of Pharmacology and Experimental Therapeutics, vol. 187, no. 1, pp. 211–217, 1973.
[41]
D. C. Gaze, “The role of existing and novel cardiac biomarkers for cardioprotection,” Current Opinion in Investigational Drugs, vol. 8, no. 9, pp. 711–717, 2007.
[42]
N. P. Yadav and V. K. Dixit, “Hepatoprotective activity of leaves of Kalanchoe pinnata Pers,” Journal of Ethnopharmacology, vol. 86, no. 2-3, pp. 197–202, 2003.
[43]
N. Kanchana and M. A. Sadiq, “Hepatoprotective effect of Plumbago zeylanica on paracetamol induced liver toxicity in rats,” International Journal of Pharmacy and Pharmaceutical Sciences, vol. 3, no. 1, pp. 151–154, 2011.
[44]
R. P. Simon, H. V. Patel, and K. Kiran, “Hepatoprotective activity of some plants extract against paracetamol induced hepatotoxicity in rats,” Journal of Herbal Medicine and Toxicology, vol. 4, no. 2, pp. 101–106, 2010.
[45]
B. Singh, A. Saxena, B. K. Chandan et al., “Hepatoprotective activity of verbenalin on experimental liver damage in rodents,” Fitoterapia, vol. 69, no. 2, pp. 135–140, 1998.
[46]
V. J. Navarro and J. R. Senior, “Drug-related hepatotoxicity,” The New England Journal of Medicine, vol. 354, no. 7, pp. 731–739, 2006.
[47]
H. Malhi, G. J. Gores, and J. J. Lemasters, “Apoptosis and necrosis in the liver: a tale of two deaths?” Hepatology, vol. 43, no. 2, pp. S31–S44, 2006.
[48]
G. Amresh, C. V. Rao, and P. N. Singh, “Antioxidant activity of Cissampelos pareira on benzo(a)pyrene-induced mucosal injury in mice,” Nutrition Research, vol. 27, no. 10, pp. 625–632, 2007.
[49]
M. B. Kadiiska, B. C. Gladen, D. D. Baird et al., “Biomarkers of oxidative stress study: are plasma antioxidants markers of CCl4 poisoning?” Free Radical Biology and Medicine, vol. 28, no. 6, pp. 838–845, 2000.
[50]
R. P. Hewawasam, K. A. P. W. Jayatilaka, C. Pathirana, and L. K. B. Mudduwa, “Protective effect of Asteracantha longifolia extract in mouse liver injury by carbon tetrachloride and paracetamol,” Journal of Pharmacy and Pharmacology, vol. 55, no. 10, pp. 1413–1418, 2003.
[51]
S. R. Naik, “Antioxidants and their role in biological functions: an overview,” Indian Drugs, vol. 40, no. 9, pp. 501–516, 2003.
[52]
R. Singh, B. Singh, S. Singh, N. Kumar, S. Kumar, and S. Arora, “Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.) Willd. Ex. Del,” Toxicology in Vitro, vol. 22, no. 8, pp. 1965–1970, 2008.
[53]
N. S. Brahma, R. S. Braj, B. K. Sarma, and H. B. Singh, “Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark,” Chemico-Biological Interactions, vol. 181, no. 1, pp. 20–28, 2009.
