Grape Juice Concentrate Protects Rat Liver Against Cadmium Intoxication: Histopathology, Cytochrome C and Metalloproteinases Expression

C. F. G. de Moura; F. A. P. Ribeiro; B. A. Handan; O. Aguiar; C. T. F. Oshima; D. A. Ribeiro

doi:10.1055/s-0035-1569452

Drug Research, Table of Contents

Drug Res (Stuttg) 2016; 66(07): 339-344
DOI: 10.1055/s-0035-1569452

Original Article

Grape Juice Concentrate Protects Rat Liver Against Cadmium Intoxication: Histopathology, Cytochrome C and Metalloproteinases Expression

Authors

C. F. G. de Moura

¹Departments of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil
F. A. P. Ribeiro

¹Departments of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil
B. A. Handan

¹Departments of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil
O. Aguiar

¹Departments of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil
C. T. F. Oshima

²Departments of Pathology, Federal University of Sao Paulo, UNIFESP, SP, Brazil
D. A. Ribeiro

¹Departments of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil

Abstract

The aim of this study was to investigate if grape juice concentrate is able to protect rat liver against cadmium toxicity. For this purpose, histopathological analysis, cytochrome C expression and immunoexpresssion of metalloproteinases (MMP) 2 and 9 were investigated. A total of 15 Wistar rats weighing 250 g on the average, and 8 weeks age were distributed into 3 groups (n=5), as follows: Control group (non-treated group, CTRL); Cadmium group (Cd) and grape juice concentrate group (Cd+GJ). Histopathological analysis revealed that liver from animals treated with grape juice concentrate improved tissue degeneration induced by cadmium intoxication. Animals intoxicated with cadmium and treated with grape juice concentrate showed higher cytochrome C gene expression in liver cells. No significant statistically differences (p>0.05) were found to MMP 2 and 9 immunoexpression between groups. Taken together, our results demonstrate that grape juice concentrate is able to prevent tissue degeneration in rat liver as a result of increasing apoptosis.

Key words

grape juice concentrate - cadmium - rat - cytochrome C - metalloproteinases

Full Text

References

References
1 World Health Organization. http://www.who.int/whr/2003 Assessed November, 23, 2015 2003
2 Fingerhut M, Nelson DI, Driscoll T et al. The contribution of occupational risks to the global burden of disease: summary and next steps. Med Lav 2006; 97: 313-321
3 Rappaport SM. Discovering environmental causes of disease. J Epidemiol Community Health 2012; 66: 99-102
4 Wasi S, Tabrez S, Ahmad M. Toxicological effects of major environmental pollutants: an overview. Environ Monit Assess 2013; 185: 2585-2593
5 Hou L, Zhang X, Wang D et al. Environmental chemical exposures and human epigenetics. Int J Epidemiol 2012; 41: 79-105
6 Edwards JR, Kolman K, Lamar PC et al. Effects of cadmium on the sub-cellular localization of β-catenin and β-catenin-regulated gene expression in NRK-52E cells. Biometals 2013; 26: 33-42
7 Rani A, Kumar A, Lal A et al. Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res 2014; 24: 378-399
8 Bernhoft RA. Cadmium toxicity and treatment. Sci World J 2013; 394652
9 de Jesus GP, Ribeiro FA, de Moura CF et al. Anti-tumor activity of grape juice concentrate in the rat tongue two-stage initiation-promotion protocol induced by 4 nitroquinoline 1-oxide. Toxicol Mech Methods 2014; 24: 276-283
10 Gollucke AP, Peres RC, Odair Jr A et al. Polyphenols: a nutraceutical approach against diseases. Recent Pat Food Nutr Agric 2013; 5: 214-219
11 Xia EQ, Deng GF, Guo YJ et al. Biological activities of polyphenols from grapes. Int J Mol Sci 2010; 11: 622-646
12 Gollücke AP, Ribeiro DA. Use of grape polyphenols for promoting human health: a review of patents. Recent Pat Food Nutr Agric 2012; 4: 26-30
13 Hasler CM, Brown AC. American Dietetic Association. Position of the American Dietetic Association: functional foods. J Am Diet Assoc 2009; 109: 735-746
14 Aguiar Jr O, Gollücke AP, de Moraes BB et al. Grape juice concentrate prevents oxidative DNA damage in peripheral blood cells of rats subjected to a high-cholesterol diet. Br J Nutr 2011; 105: 694-702
15 da Silva VH, de Moura CF, Ribeiro FA et al. Genotoxicity and cytotoxicity induced by municipal effluent in multiple organs of Wistar rats. Environ Sci Pollut Res Int 2014; 21: 13069-13080
16 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-159
17 Nair PM, Park SY, Chung JW et al. Transcriptional regulation of glutathione biosynthesis genes, γ-glutamyl-cysteine ligase and glutathione synthetase in response to cadmium and nonylphenol in Chironomus riparius. Environ Toxicol Pharmacol 2013; 36: 265-273
18 Matović V, Buha A, Bulat Z et al. Cadmium toxicity revisited: focus on oxidative stress induction and interactions with zinc and magnesium. Arh Hig Rada Toksikol 2011; 62: 65-76
19 Tomaszewska E, Winiarska-Mieczan A, Dobrowolski P. Hematological and serum biochemical parameters of blood in adolescent rats and histomorphological changes in the jejunal epithelium and liver after chronic exposure to cadmium and lead in the case of supplementation with green tea vs black, red or white tea. Exp Toxicol Pathol 2015; 67: 331-339
20 Dkhil MA, Al-Quraishy S, Diab MM et al. The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity. Food Chem Toxicol 2014; 74: 98-106
21 Claudio SR, Gollucke AP, Yamamura H et al. Purple carrot extract protects against cadmium intoxication in multiple organs of rats: Genotoxicity, oxidative stress and tissue morphology analyses. J Trace Elem BIol Med 2016; 33: 37-47
22 Tong X, Lin S, Fujii M et al. Echinocystic acid induces apoptosis in HL-60 cells through mitochondria-mediated death pathway. Cancer Lett 2014; 212: 21-32
23 Fujimura M, Morita-Fujimura Y, Copin J et al. Reduction of copper, zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia. Brain Res 2001; 889: 208-213
24 Cai J, Jones DP. Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss. J Biol Chem 1998; 273: 11401-11404
25 Alpsoy S, KanterM Aktas C. et al. Protective effects of onion extract on cadmium-induced oxidative stress, histological damage,and apoptosis in rat heart. Biol Trace Elem Res 2014; 159: 297-303
26 Jiang C, Yuan Y, Hu F et al. Cadmium induces PC12 cells apoptosis via an extracellular signal-regulated kinase and c-Jun N-terminal kinase-mediated mitochondrial apoptotic pathway. Biol Trace Elem Res 2014; 158: 249-258
27 Pham T, Marion M, Denizeau F et al. Cadmium-induced apoptosis in rat hepatocytes does not necessarily involve caspase-dependent pathways. Toxicol in Vitro 2006; 20: 1331-1342
28 Wang J, Zhu H, Liu X et al. Oxidative stress and Ca(2 +) signals involved on cadmium-induced apoptosis in rat hepatocyte. Biol Trace Elem Res 2014; 161: 180-189
29 Yuan G, Dai S, Yin Z et al. Sub-chronic lead and cadmium co-induce apoptosis protein expression in liver and kidney of rats. Int J Clin Exp Pathol 2014; 7: 2905-2914
30 Korhunov SS, Krasnikov BF, Pereverzev MO et al. The antioxidant functions of cytochrome C. FEBS Lett 1999; 462: 192-198
31 Nakano M, Kimura H, Hara M et al. A highly sensitive method for determining both Mn- and Cu-Zn superoxide dismutase activities in tissues and blood cells. Anal Biochem 1990; 187: 277-280
32 Ullah I, Park HY, Kim MO. Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons. CNS Neurosci Ther 2014; 20: 327-338
33 Hui C, Bin Y, Xiaoping Y et al. Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo. Nutr Cancer 2010; 62: 1128-1136
34 Oshima CT, Landman G, Paiotti AP et al. Grape juice concentrate (G8000™) modulates apoptosis but not oxidative stress following rat colon carcinogenesis induced by azoxymethane. Toxicol Mech Methods 2015; 25: 91-97
35 Ferreira AO, Gollücke AP, Noguti J et al. Grape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats. Toxicol Mech Methods 201 22: 218-224
36 Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002; 295: 2387-2392
37 Fracalossi AC, Miranda SR, Oshima CT et al. The role of matrix metalloproteinases 2 and 9 during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. J Mol Histol 2010; 41: 19-25
38 Person RJ, Tokar EJ, Xu Y et al. Chronic cadmium exposure in vitro induces cancer cell characteristics in human lung cells. Toxicol Appl Pharmacol 2013; 273: 281-288
39 Lian S, Xia Y, Khoi PN et al. Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-кB, and AP-1 pathways in human endothelial cells. Toxicology 2015; 11 338: 104-116
40 Lacorte LM, Rinaldi JC, Justulin Jr LA et al. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis. Biochem Biophys Res Commun 2015; 457: 538-541
41 Lee J, Lim KT. Inhibitory effect of plant-originated glycoprotein (27 kDa) on expression of matrix metalloproteinase-9 in cadmium chloride-induced BNL CL.2 cells. J Trace Elem Med Biol 2011; 25: 239-246