Cadmium induced hepatic intoxication and amelioration by grape seed extract


  • Adel Adel Alkhedaide Associate prof
  • Gehan Youssef lecturarl
  • Rabab El-Zoghby Assistant prof
  • Mohamed Mahmoud lectural
  • Shimaa Atwa lectural





Cadmium, Grape seed extract, Intoxication, Liver


Cadmium (Cd) is wide-spread toxic metal that pollutes most of the vegetables, which eaten by numerous populations all over the world. The aim of the current work is to evaluate the protective and prophylactic effects of the antioxidant materials in the grape seed extract (GSE) on the hepatic intoxication induced by cadmium chloride toxic material in male Wistar rats. Male adult Wistar rats were divided into four groups. Control group fed on balanced diet and given drinking water. Group two (control positive) given CdCl2 in the dose of 0.44 mg/kg body weight (BW) by stomach tube daily. Group three given grape seed extract GSE in the dose of (100 mg/kg BW) daily by stomach tube. Finally, the fourth group gave mixture of (GSE and CdCl2) by stomach tube in the recommended dose. Blood and liver tissues were collected for further biochemical and histopathological studies. CdCl2 significantly increased the serum levels of malondialdehyde, ALT and AST. Cadmium administration decreased levels of antioxidants (Catalase, GSH-R and GSH-Px). The liver of the control positive groups which given CdCl2 showed degenerative changes in the form of vacuolar and hydropic degeneration. Congestion was evident in the central vein and proliferation of the kupffer cells. These hepatic biochemical and degenerative changes were ameliorated by the co addition of GSE.


[1] Adebajo AC, Iwalewa EO, Obuotor EM, Ibikunle GF, Omisore NO, Adewunmi CO, Obaparusi OO, Klaes M, Adetogun GE, Schmidt TJ & Verspohl EJ (2009). Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: Anti-trichomonal, antidiabetic, anti-inflammatory, hepatoprotective and antioxidant effects. Journal of Ethnopharmacology 122, 10-19.

[2] Aebi H (1984). Catalase in vitro. Methods in enzymology 105, 121-126.

[3] AFDOAQ, Association of Food and Drug Officials of the United States, Quart. Bull. 1951; 15: 122-125.

[4] Al-Alawi MTM & Mandiwana KL (2007). The use of Aleppo pine needles as a bio-monitor of heavy metals in the atmosphere. Journal of Hazardous Materials 148, 43-46.

[5] Albasha MO & Azab S (2014). Effect of cadmium on the liver and amelioration by aqueous extracts of fenugreek seeds, rosemary, and cinnamon in Guinea pigs: histological and biochemical study. Cell Biol 2, 7-17.

[6] Alkedaide AQ (2015): The Anti-inflammatory effect of grape seed extract in rats exposed to Cadmium Chloride toxicity International Journal of Advanced Research Volume 3, Issue 7, 298-305.

[7] Alkhedaide A, Alshehri ZS, Sabry A, Abdel-Ghaffar T, Soliman MM & Attia H (2016). Protective effect of grape seed extract against cadmium-induced testicular dysfunction. Molecular Medicine Reports 13, 3101-3109.

[8] Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS & Pruess HG (2000). Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148, 187-197.

[9] Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX & Stohs SJ (1997). Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95, 179-89.

[10] Bancroft J & Gamble A (2002). Theory and Practice of Histological Techniques, New York and London, Churchil, Living stone.

[11] Bashir N, Manoharan V & Prabu M (2014). Ameliorative effects of grape seed proanthocyanidins on cadmium induced metabolic alterations in rats. International Journal of Biological Research 2.

[12] Beutler E, Duron O & Kelly BM (1963). Improved method for the determination of blood glutathione. J Lab Clin Med 61, 882-8.

[13] Cetin A1, Kaynar L, Koçyiğit I, Hacioğlu SK, Saraymen R, Oztürk A, Orhan O, Sağdiç O. (2008). The effect of grape seed extract on radiation-induced oxidative stress in the rat liver. Turk J Gastroenterol; 19(2):92-8.

[14] Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Opdenakker K, Nair AR, Munters E & Artois TJ (2010). Cadmium stress: an oxidative challenge. Biometals 23, 927-940.

[15] Dudley RE, Svoboda DJ & Klaassen CD (1982). Acute exposure to cadmium causes severe liver injury in rats. Toxicology and applied pharmacology 65, 302-313.

[16] Dudley RE, Svoboda DJ & Klaassen CD (1984). Time course of cadmium-induced ultrastructural changes in rat liver. Toxicology and applied pharmacology 76, 150-160.

[17] Dulundu E, Ozel Y, Topaloglu U, Toklu H, Ercan F, Gedik N & Åžener G (2007). Grape seed extract reduces oxidative stress and fibrosis in experimental biliary obstruction. Journal of Gastroenterology and Hepatology 22, 885-892.

[18] Eisler R (2000). Cadmium, Florida, CRC Press.

[19] El-Sharaky AS, Newairy AA, Badreldeen MM, Eweda SM & Sheweita SA (2007). Protective role of selenium against renal toxicity induced by cadmium in rats. Toxicology 235, 185-193.

[20] El-Sokkary GH, Nafady AA & Shabash EH (2010). Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat. Ecotoxicology and Environmental Safety 73, 456-463.

[21] El-Tarras AE-S, Attia HF, Soliman MM, El Awady MA & Amin AA (2016). Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats. International Journal of Immunopathology and Pharmacology 29, 398-407.

[22] Ferreira D & Li X-C (2000). Oligomeric proanthocyanidins: naturally occurring O-heterocycles. Natural product reports 17, 193-212.

[23] García-Alonso M, Rimbach G, Rivas-Gonzalo JC & De Pascual-Teresa S (2004). Antioxidant and Cellular Activities of Anthocyanins and Their Corresponding Vitisins AStudies in Platelets, Monocytes, and Human Endothelial Cells. Journal of Agricultural and Food Chemistry 52, 3378-3384.

[24] Gathwan K, Al Ameri, Qma, Zaidan H, Al Saadi A & And Ewadh M (2012). Heavy metals induce apoptosis in liver of mice. Inter J Appl Biol Pharmacol Technol 3, 146-150.

[25] Goyer R (1986). Toxic effects of metals. In: J Doull CK, And Mo Amdur (ed.) Cassrett and Doull’s Toxicology. New York: Macmillian, pp. 582–635

[26] Grattagliano I, Bonfrate L, Diogo CV, Wang HH, Wang DQ & Portincasa P (2009). Biochemical mechanisms in drug-induced liver injury: certainties and doubts. World journal of gastroenterology: WJG 15, 4865.

[27] Gu L, Kelm M, Hammerstone JF, Beecher G, Cunningham D, Vannozzi S & Prior RL (2002). Fractionation of Polymeric Procyanidins from Lowbush Blueberry and Quantification of Procyanidins in Selected Foods with an Optimized Normal-Phase HPLC−MS Fluorescent Detection Method. Journal of Agricultural and Food Chemistry 50, 4852-4860.

[28] Halpern MJ, Dahlgren AL, Laakso I, Seppänen-Laakso T, Dahlgren J & Mcanulty PA (1998). Red-wine Polyphenols and Inhibition of Platelet Aggregation: Possible Mechanisms, and Potential Use in Health Promotion and Disease Prevention. Journal of International Medical Research 26, 171-180.

[29] Ho C-T, Ferraro T, Chen Q, Rosen RT & Huang M-T. (1994). Phytochemicals in Teas and Rosemary and Their Cancer-Preventive Properties. ACS Symposium Series. American Chemical Society, 2-19.

[30] Huang X-J, Choi Y-K, Im H-S, Yarimaga O, Yoon E & Kim H-S (2006). Aspartate Aminotransferase (AST/GOT) and Alanine Aminotransferase (ALT/GPT) Detection Techniques. Sensors 6, 756-782.

[31] Hwang DA & Wang L (2001). Effect of taurine on toxicity of cadmium in rats. Toxicology 167, 173-180.

[32] Jurczuk M, M. Brzóska M, Moniuszko-Jakoniuk J, Gałażyn-Sidorczuk M & Kulikowska-Karpińska E (2004). Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food and Chemical Toxicology 42, 429-438.

[33] Kara H, Fikret Karataþ & Canatan H (2005). Effect of Single Dose Cadmium Chloride Administration on Oxidative Stress in Male and Female Rats. Turk J Vet Anim Sci 29 37-42.

[34] Katiyar SK (2008). Grape seed proanthocyanidines and skin cancer prevention: inhibition of oxidative stress and protection of immune system. Mol Nutr Food Res 52 Suppl 1, S71-6.

[35] Kiernan J (2008). Histological and Histochemical Methods: Theory and Practice., USA, Bloxham: Scion publishing.

[36] Koyu A, Gokcimen A, Ozguner F, Bayram DS & Kocak A (2006). Evaluation of the effects of cadmium on rat liver. Molecular and Cellular Biochemistry 284, 81-85.

[37] Kris-Etherton PM & Keen CL (2002). Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Current Opinion in Lipidology 13, 41-49.

[38] Li WG, Zhang XY, Wu YJ & Tian X (2002). Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds.

[39] Mahran A, Osman H, El-Mawla A & Attia A (2011). Protective effect of zinc (Zn) on the histology and histochemistry of liver and kidney of albino rat treated with cadmium. J Cytol Histol 2, 2-9.

[40] Nair V, O'neil CL & Wang PG (2008). Malondialdehyde. Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons, Ltd, pp.

[41] Ohkawa H, Ohishi N & Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95, 351-358.

[42] Oki T, Masuda M, Kobayashi M, Nishiba Y, Furuta S, Suda I & Sato T (2002). Polymeric Procyanidins as Radical-Scavenging Components in Red-Hulled Rice. Journal of Agricultural and Food Chemistry 50, 7524-7529.

[43] Paglia DE & Valentine WN (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70, 158-169.

[44] Pathak N & Khandelwal S (2006). Oxidative stress and apoptotic changes in murine splenocytes exposed to cadmium. Toxicology 220, 26-36.

[45] Pillai A & Gupta S (2005). Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: Effects of vitamin E and Mn2+. Free Radical Research 39, 707-712.

[46] Reeves PG & Rossow KL (1996). Zinc-and/or cadmium-induced intestinal metallothionein and copper metabolism in adult rats. The Journal of Nutritional Biochemistry 7, 128-134.

[47] Renugadevi J & Prabu SM (2010). Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Experimental and Toxicologic Pathology 62, 171-181.

[48] Rikans LE & Yamano T (2000). Mechanisms of cadmium-mediated acute hepatotoxicity. Journal of Biochemical and Molecular Toxicology 14, 110-117.<110::AID-JBT7>3.0.CO;2-J.

[49] Robbins S & Angell M (1976). Basic Pathology, Phildelphia, London,, W.B.Saunders Company.

[50] Sehirli O, Ozel Y, Dulundu E, Topaloglu U, Ercan F & Sener G (2008). Grape seed extract treatment reduces hepatic ischemia-reperfusion injury in rats. Phytother Res 22, 43-8.

[51] Suru SM (2008). Onion and garlic extracts lessen cadmium-induced nephrotoxicity in rats. Biometals 21, 623-633.

[52] Suzuki Y, Morita I, Yamane Y & Murota S-I (1989). Cadmium stimulates prostaglandin E2 production and bone resorption in cultured fetal mouse calvaria. Biochemical and Biophysical Research Communications 158, 508-513.

[53] Swiergosz-Kowalewska R (2001). Cadmium distribution and toxicity in tissues of small rodents. Microsc Res Tech 55, 208-22.

[54] Theocharis S, Margeli A, Fasitsas C, Loizidou M & Deliconstantinos G (1991). Acute exposure to cadmium causes time-dependent liver injury in rats. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology 99, 127-130.

[55] Thévenod F (2003). Nephrotoxicity and the proximal tubule. Nephron Physiology 93, 87-93.

[56] Waisberg M, Joseph P, Hale B & Beyersmann D (2003). Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 192, 95-117.

[57] Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA & Kris-Etherton PM (2001). Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. The American journal of clinical nutrition 74, 596-602.

[58] Wong L, Whitehouse L, Solomonraj G & Paul C (1981). Pathways of disposition of acetaminophen conjugates in the mouse. Toxicology letters 9, 145-151.

[59] Wynne B (1999). Agency for Toxic Substances and Disease Registry (ATSDR). Encyclopedia of Global Health. SAGE Publications, Inc., pp.

[60] Zikic R, Stajn A, Saicic Z, Spasic M, Ziemnicki K & Petrovic V (1996). The activities of superoxide dismutase, catalase and ascorbic acid content in the liver of goldfish (Carassius auratus gibelio Bloch.) exposed to cadmium. Physiological research 45, 479-481.

View Full Article: