Preventative Effects of Caffeic Acid Phenyl Ester on Cadmium Intoxication Induced Hematological and Blood Coagulation Disturbances and Hepatorenal Damage in Rats
The preventative effect of caffeic acid phenyl ester (CAPE) against hematological, blood coagulation, and hepatorenal disturbances in cadmium (Cd) intoxication was investigated in rats. Male Wistar rats were randomly assigned into control group, Cd-group, and Cd + CAPE group. Cd intoxication was induced by intraperitoneal injection (i.p.) of CdCl2 (1？mg/kg/day) for 21 days, and CAPE was daily given (10 micromol/kg; i.p.) for also 21 days. The results showed that Cd intoxication impaired hepatorenal function and significantly prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen level, red blood cells and platelets counts, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Interestingly, all these hematological, blood coagulation, and hepatorenal deteriorations of Cd toxicity were significantly prevented by CAPE. Additionally, CAPE significantly reversed the significant decreases in levels of total reduced glutathione and superoxide dismutase and increases in levels of thiobarbituric acid reactive substances that were observed in the sera and liver and kidney homogenates of Cd group. It is concluded that CAPE is a promising compound that can counteract the hematological and blood coagulation disturbances, oxidative stress, and hepatorenal damages in Cd intoxication. However, further studies are crucially needed to improve this treatment in patients. 1. Introduction Caffeic acid phenyl ester (CAPE) is one of the main medicinal components of honeybee propolis that possesses a variety of biological and pharmacological actions such as potent free radical scavenging, antioxidant, anti-inflammatory, cytoprotective, immunomodulatory, and antiviral and promising anticancer properties [1]. Also, the ameliorating and counteracting effects of CAPE on different disease modalities of hematological, blood coagulation, and vascular abnormalities have recently been emerged. In this concept, CAPE had shown to ameliorate blood coagulation abnormalities and disturbed oxidative stress in endotoxic model of acute liver failure [2], increase cerebral blood flow and improve ischemic stroke in neurovascular disease [3], protect peripheral blood mononuclear cells against hyperthermal stress [4], prevent drugs to induce toxic and damage effects on red blood cells [5], and potently inhibit the synthesis of inflammatory and atherosclerotic leukotrienes in human polymorphonuclear leukocytes and whole blood [6]. Cadmium (Cd) is classified as a very harmful
References
[1]
S. Akyol, G. Ozturk, Z. Ginis, F. Armutcu, M. R. Yigitoglu, and O. Akyol, “In vivo and in vitro ant？neoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives,” Nutrition and Cancer, vol. 65, no. 4, pp. 515–526, 2013.
[2]
A. A. Korish, “Effect of caffeic acid phenethyl ester on the hemostatic alterations associated with toxic-induced acute liver failure,” Blood Coagulation and Fibrinolysis, vol. 21, no. 2, pp. 158–163, 2010.
[3]
M. Khan, C. Elango, M. A. Ansari, I. Singh, and A. K. Singh, “Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat brain following transient focal cerebral ischemia,” Journal of Neurochemistry, vol. 102, no. 2, pp. 365–377, 2007.
[4]
Y.-J. Chen, A.-C. Huang, H.-H. Chang et al., “Caffeic acid phenethyl ester, an antioxidant from propolis, protects peripheral blood mononuclear cells of competitive cyclists against hyperthermal stress,” Journal of Food Science, vol. 74, no. 6, pp. H162–H167, 2009.
[5]
O. Gokalp, E. Uz, E. Cicek et al., “Ameliorating role of caffeic acid phenethyl ester (CAPE) against isoniazid-induced oxidative damage in red blood cells,” Molecular and Cellular Biochemistry, vol. 290, no. 1-2, pp. 55–59, 2006.
[6]
L. H. Boudreau, J. Maillet, L. M. LeBlanc et al., “Caffeic acid phenethyl ester and its amide analogue are potent inhibitors of leukotriene biosynthesis in human polymorphonuclear leukocytes,” PLoS ONE, vol. 7, no. 2, Article ID e31833, 2012.
[7]
E. H. Jihen, M. Imed, H. Fatima, and K. Abdelhamid, “Protective effects of selenium (Se) and zinc (Zn) on cadmium (Cd) toxicity in the liver of the rat: effects on the oxidative stress,” Ecotoxicology and Environmental Safety, vol. 72, no. 5, pp. 1559–1564, 2009.
[8]
P. Gong, F. Chen, X. Liu, X. Gong, J. Wang, and Y. Ma, “Protective effect of caffeic acid phenethyl ester against cadmium-induced renal damage in mice,” Journal of Toxicological Sciences, vol. 37, no. 2, pp. 415–425, 2012.
[9]
R. Hambach, D. Lison, P. C. D'Haese et al., “Co-exposure to lead increases the renal response to low levels of cadmium in metallurgy workers,” Toxicology Letters, vol. 22, no. 2, pp. 233–238, 2013.
[10]
U. S. Department of Health Services, “Toxicological profile for cadmium,” Draft for Public Comment, Agency for Toxic Substances and Disease Registry, Atlanta, Ga, USA, 1997.
[11]
C. Simpkins, T. Lloyd, S. Li, and S. Balderman, “Metallothionein-induced increase in mitochondrial inner membrane permeability,” Journal of Surgical Research, vol. 75, no. 1, pp. 30–34, 1998.
[12]
M. M. Kosti？, B. Ognjanovi？, R. V. Ziki？, et al., “Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects,” European Journal of Haematology, vol. 51, pp. 86–92, 1993.
[13]
M. Kanter, O. Coskun, and A. Gurel, “Effect of black cumin (Nigella sativa) on cadmium-induced oxidative stress in the blood of rats,” Biological Trace Element Research, vol. 107, no. 3, pp. 277–287, 2005.
[14]
M. W. Fariss, “Cadmium toxicity: unique cytoprotective properties of alpha tocopheryl succinate in hepatocytes,” Toxicology, vol. 69, no. 1, pp. 63–77, 1991.
[15]
H. Mollaoglu, A. Gokcimen, F. Ozguner et al., “Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat,” Toxicology, vol. 227, no. 1-2, pp. 15–20, 2006.
[16]
F. Chen and P. Gong, “Caffeic acid phenethyl ester protects mice hepatic damage against cadmium exposure,” Procedia Environmental Sciences, vol. 8, pp. 633–636, 2011.
[17]
A. Kobroob, N. Chattipakorn, and O. Wongmekiat, “Caffeic acid phenethyl ester ameliorates cadmium-induced kidney mitochondrial injury,” Chemico-Biological Interactions, vol. 200, no. 1, pp. 21–27, 2012.
[18]
C. Lemini, R. Jaimez, and Y. Franco, “Gender and inter-species influence on coagulation tests of rats and mice,” Thrombosis Research, vol. 120, no. 3, pp. 415–419, 2007.
[19]
A. Akesson, “Cadmium exposure in the environment: renal effects and the benchmark dose,” in Encyclopedia of Environmental Health, O. N. Jerome, Ed., pp. 465–473, Elsevier, Burlington, Canada, 2011.
[20]
G. Yuan, S. Dai, Z. Yin et al., “Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats,” Food and Chemical Toxicology, vol. 65, pp. 260–268, 2014.
[21]
J. W. Bauman, J. Liu, and C. D. Klaassen, “Production of metallothionein and heat-shock proteins in response to metals,” Fundamental and Applied Toxicology, vol. 21, no. 1, pp. 15–22, 1993.
[22]
V. B. Liju, K. Jeena, and R. Kuttan, “Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L.),” Food and Chemical Toxicology, vol. 53, pp. 52–61, 2013.
[23]
T. S. Gill and A. Epple, “Stress-related changes in the hematological profile of the American Eel (Anguilla rostrata),” Ecotoxicology and Environmental Safety, vol. 25, no. 2, pp. 227–235, 1993.
[24]
B. I. Ognjanovi？, S. Z. Pavlovi？, S. D. Maleti？ et al., “Protective influence of vitamin E on antioxidant defense system in the blood rats treated with cadmium,” Physiological Research, vol. 52, pp. 563–570, 2003.
[25]
L. Amitrano, M. A. Guardascione, V. Brancaccio, and A. Balzano, “Coagulation disorders in liver disease,” Seminars in Liver Disease, vol. 22, no. 1, pp. 83–96, 2002.
[26]
Y. Yildiz, M. Serter, R. O. Ek et al., “Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury,” Digestive Diseases and Sciences, vol. 54, no. 4, pp. 738–744, 2009.
