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Grape seed extract effects on serum amylase levels and immunohistochemical alterations in Streptozotocin-induced diabetic rats
Corresponding Author(s) : Kıvanç Irak
Cellular and Molecular Biology,
Vol. 64 No. 4: Issue 4
Abstract
In this study, serum amylase activity and structural changes of the pancreatic tissue in rats under the effects of grape seed extract were investigated. Thirty-two female Wistar albino rats were divided into 4 groups. First one was the control group. The second group was the streptozotocin (STZ)-induced diabetes mellitus (DM) group (45 mg/kg), while the third group was the grape seed extract (GSE) group, where the GSE was administrated intragastrically for 20 days (at 0.6 ml/rat). Lastly, the fourth group was the diabetes mellitus+GSE (DM+GSE) group. Blood samples were taken and analyzed for amylase activity. Caspase 3 expressions were inspected with immunohistochemistry. Amylase levels in the diabetic group were found to be the lowest (794.00±44.85 U/L, p<0.001), while the GSE group had the highest value (1623.63±80.04 U/L, p<0.001) Number of apoptotic cells was increased in Langerhans islets of the diabetic group. In the control and GSE groups, the apoptotic cells were found to be almost entirely absent. Increased number of apoptotic cells was found in the DM group, while decreased number of apoptotic cells was found in the DM+GSE group. Furthermore, atrophy in Langerhans islets, hyperemia in capillary veins, hydropic degeneration and necrosis in islet cells were determined in the diabetic group. Only mild hydropic degeneration in islet cells of Langerhans was observed in the DM+GSE group. Histopathologically beneficial changes in the pancreases were detected when grape seed extract was given to diabetic rats. As a conclusion, GSE was determined to have positive effects on the function and structure of the pancreas, improving enzyme activities and the structure of the Langerhans islets.
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- REFERENCES
- Durna Z. Diyabetin Sınıflandırılması ve Tanı Kriterleri, Ed. S. Erdoğan, Diyabet Hemşireliği, Yüce Reklam Yayın Dağıtım A.Åž., 2002, 11-19, ć°stanbul.
- Spanheimer RG, Umpierrez GE, Stumf V. Decreased collagen production in diabetic rats. Diabetes 1988; 37: 371-376.
- Pieper-Bigelow C, Strocchi A, Levitt MD. Where does serum amylase come from and where does it go? Gastroenterol Clin North Am 1990; 19: 793-810.
- Witters LA. The blooming of the French lilac. J. Clin. Invest. 2001; 108, 1105-1107.
- Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: structure activity relationships, Free Radic Biol Med 1997; 22: 749-760.
- í–zel Y. Ratlarda karaciğer iskemi/reperfüzyon hasarında grape seed proanthocyanidinin koruyucu etkilerinin incelenmesi, Uzmanlık Tezi, Sağlık Bakanlığı, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, 5. Genel Cerrahi Kliniği, 2006, ć°stanbul.
- Takahashi T, Koboyashi A Proanthocyanidin-containing composition, United Patent Office 2003; 6:506, 419.
- Shahidi F, Wanasundara PK. Phenolic antioxidants. Crit Rev Food Sci Nutr 1992; 32(1): 67–103. Review.
- Udaya FS, Wanasundara N, Amarowicz R. Natural antioxidants from low-pungency mustard flour. Food Res Int. 1994; 27(5): 489–493.
- Wadsworth TL, Koop DR Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in ram 264,7 macrophages. Biochem Pharmacol 1999; 57: 941-949.
- Shi J, Yu J, Pohorly JE, Kakuda Y Polyphenolics in grape seeds-biochemistry and functionality. J Med Food 2003; 6(4): 291–299.
- Hıkım APS, Wang C, Leung AR, Swerdloff S. Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment. Endocrinology 1995; 136(6): 2770-2775.
- Mcphie DL, Coopersmith R, Peralta A H, Chen Y, Ivins KJ, Manly SP et al. DNA synthesis and neuronal apoptosis caused by familial alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. The Journal of Neuroscience 2003; 23(17): 6914–6927.
- Wright SC, Wei QS, Kinder D H, Larrick JW Biochemical pathways ofapoptosis; nicotinamide adenine dinucleotide-deficient cells are resistant to tumor necrosis factor or ultraviolet light activation of the 24-kd apoptotic protease and DNA fragmentation. J. Exp. Med. 1996; 183: 463-471.
- Karabay G, Zağyapan R, Take G Streptozotosinle oluşturulan diabetin sıçan periferik sinirleri üzerine etkisinin elektron mikroskobik incelenmesi, Uludağ íœniversitesi Tıp Fakültesi Dergisi 2006; 32(3): 77-81.
- Chis IC, Ungureanu MI, Marton A, et al. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus. Diabetes Vasc Dis Res. 2009; 6:200–204
- Taylor CR, Shi S-R, Barr NJ. Techniques of Immunohistochemistry: principles, pitfalls, and standardization. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 3rd ed. Philadelphia: Saunders-Elsevier 2010; p. 1-41
- Jimenez-Ramsey LM, Rogler JC, Housley TL, Butler LG, Eklin RG. Absorption and distribution of 14 C-labeled condensed tannins and related sorghum phenolics in chickens. J Argic Food Chem 1994; 42: 963–967.
- Belviranlı M, Gökbel H, Okudan N, Büyükbaş S. Oxidative stress and anti-oxidant status in diabetic rat liver: effect of plant polyphenols, Arch Physiol Biochem 2012; 118 (5): 237-243.
- Evans J. L., Goldfine I. D., Maddux B. A., Grodsky G. M. (). Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003; 52: 1–810.
- Pazdro R, Burgess JR. The role of vitamin E and oxidative stress in diabetes complications. Mech Ageing Dev 2010; 131: 276–286.
- Mollaoğlu H, Yılmaz H R, Gökalp O, Altuntaş ć° . Methidathion'un Pankreas íœzerine Etkileri: Vitamin E ve C'nin Rolü. Van Tıp Dergisi 2003; 10(4): 98-100.
- Nonaka A, Manabe T, Tobe T. Effect of a new synthetic ascorbic acid derivative as a free radical scavenger on the development of acute pancreatitis in mice. Gut 1991; 32(5): 528-532.
- Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J. Shoelson SE Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappa B. Nat. Med 2005; 11: 183–190.
- Chen WP, Chi TC, Chuang LM, Su MJ. Resveratrol enhances insulin secretion by blocking KATP and KV channels of beta cells, Eur J Pharmacol 2007; 568: 269–277.
- Su HC, Hung LM, Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats, Am J Physiol Endocrinol Metab 2006; 290: 1339–1346.
- Toppel G, Lei B, Fraga A (2004). Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma. Free Radic Biol Med, 2004; 18(11): 895.
- Hvang IK, Kim DW, Park JH, Lim SS, Yoo KK, Kwon DY, et al. Effects of grape seed extract and its ethylacetate/ethanol fraction on blood glucose levels in a model of type 2 diabetes, Phytother Res 2009; 23(8): 1182–1185.
- Majeed Dr, Khitam HM, Rashad JS, Ghadhban F. Role of grape seed extract as anti hyperglycemia and antioxidant in experimental diabetic rats, Journal of Misan Researches 2008; 4: 8.
- Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine, Am J Enol Vitic1992; 43: 49–52.
- Waltner-Law ME, Wang XL, Law BK, Hall RK, Nawano M, Granner DK. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production, J Biol Chem 2002; 277: 34933–34940.
- Giardino I, Fard AK, Hatchell DL, Brownlee M. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation and oxidant induced apoptosis. Diabetes 1998; 47:1114-20.
- Saxena AK, Srivastava P, Kale RK, Baquer NZ. Impaired antioxidant status in diabetic rat liver. Effect of vanadate. Biochem Pharmacol 1993; 45: 539-42.
- Hasan K, Namık D. Gebelikte ve postpartum erken dönemde serbest radikal oluşumu ve antioksidan enzim düzeyleri. SDíœ Tıp Fakültesi Dergisi 1996; 3: 67-70.
- Brüne B, von Knethen A, Sandau KB. Nitric oxide and its role in apoptosis. Eur J Pharmacol 1998; 26(351): 261-72.
- Haligur M, Topsakal S, Ozmen O. Early degenerative effects of diabetes mellitus on pancreas, liver, and kidney in rats: An immunohistochemical study. Exp Diabetes Res 2012; 2012: 120645
- Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes 1999; 48: 1-9
- Irak K. The effects of grape seed extract on the some enzymes and metabolites in diabetic rats. YYU Institute of Health Sciences, Ph.D Thesis in Department of Biochemistry, 2014, Van.
References
REFERENCES
Durna Z. Diyabetin Sınıflandırılması ve Tanı Kriterleri, Ed. S. Erdoğan, Diyabet Hemşireliği, Yüce Reklam Yayın Dağıtım A.Åž., 2002, 11-19, ć°stanbul.
Spanheimer RG, Umpierrez GE, Stumf V. Decreased collagen production in diabetic rats. Diabetes 1988; 37: 371-376.
Pieper-Bigelow C, Strocchi A, Levitt MD. Where does serum amylase come from and where does it go? Gastroenterol Clin North Am 1990; 19: 793-810.
Witters LA. The blooming of the French lilac. J. Clin. Invest. 2001; 108, 1105-1107.
Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: structure activity relationships, Free Radic Biol Med 1997; 22: 749-760.
í–zel Y. Ratlarda karaciğer iskemi/reperfüzyon hasarında grape seed proanthocyanidinin koruyucu etkilerinin incelenmesi, Uzmanlık Tezi, Sağlık Bakanlığı, Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, 5. Genel Cerrahi Kliniği, 2006, ć°stanbul.
Takahashi T, Koboyashi A Proanthocyanidin-containing composition, United Patent Office 2003; 6:506, 419.
Shahidi F, Wanasundara PK. Phenolic antioxidants. Crit Rev Food Sci Nutr 1992; 32(1): 67–103. Review.
Udaya FS, Wanasundara N, Amarowicz R. Natural antioxidants from low-pungency mustard flour. Food Res Int. 1994; 27(5): 489–493.
Wadsworth TL, Koop DR Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in ram 264,7 macrophages. Biochem Pharmacol 1999; 57: 941-949.
Shi J, Yu J, Pohorly JE, Kakuda Y Polyphenolics in grape seeds-biochemistry and functionality. J Med Food 2003; 6(4): 291–299.
Hıkım APS, Wang C, Leung AR, Swerdloff S. Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment. Endocrinology 1995; 136(6): 2770-2775.
Mcphie DL, Coopersmith R, Peralta A H, Chen Y, Ivins KJ, Manly SP et al. DNA synthesis and neuronal apoptosis caused by familial alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. The Journal of Neuroscience 2003; 23(17): 6914–6927.
Wright SC, Wei QS, Kinder D H, Larrick JW Biochemical pathways ofapoptosis; nicotinamide adenine dinucleotide-deficient cells are resistant to tumor necrosis factor or ultraviolet light activation of the 24-kd apoptotic protease and DNA fragmentation. J. Exp. Med. 1996; 183: 463-471.
Karabay G, Zağyapan R, Take G Streptozotosinle oluşturulan diabetin sıçan periferik sinirleri üzerine etkisinin elektron mikroskobik incelenmesi, Uludağ íœniversitesi Tıp Fakültesi Dergisi 2006; 32(3): 77-81.
Chis IC, Ungureanu MI, Marton A, et al. Antioxidant effects of a grape seed extract in a rat model of diabetes mellitus. Diabetes Vasc Dis Res. 2009; 6:200–204
Taylor CR, Shi S-R, Barr NJ. Techniques of Immunohistochemistry: principles, pitfalls, and standardization. In: Dabbs DJ, editor. Diagnostic immunohistochemistry: theranostic and genomic applications. 3rd ed. Philadelphia: Saunders-Elsevier 2010; p. 1-41
Jimenez-Ramsey LM, Rogler JC, Housley TL, Butler LG, Eklin RG. Absorption and distribution of 14 C-labeled condensed tannins and related sorghum phenolics in chickens. J Argic Food Chem 1994; 42: 963–967.
Belviranlı M, Gökbel H, Okudan N, Büyükbaş S. Oxidative stress and anti-oxidant status in diabetic rat liver: effect of plant polyphenols, Arch Physiol Biochem 2012; 118 (5): 237-243.
Evans J. L., Goldfine I. D., Maddux B. A., Grodsky G. M. (). Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003; 52: 1–810.
Pazdro R, Burgess JR. The role of vitamin E and oxidative stress in diabetes complications. Mech Ageing Dev 2010; 131: 276–286.
Mollaoğlu H, Yılmaz H R, Gökalp O, Altuntaş ć° . Methidathion'un Pankreas íœzerine Etkileri: Vitamin E ve C'nin Rolü. Van Tıp Dergisi 2003; 10(4): 98-100.
Nonaka A, Manabe T, Tobe T. Effect of a new synthetic ascorbic acid derivative as a free radical scavenger on the development of acute pancreatitis in mice. Gut 1991; 32(5): 528-532.
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J. Shoelson SE Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappa B. Nat. Med 2005; 11: 183–190.
Chen WP, Chi TC, Chuang LM, Su MJ. Resveratrol enhances insulin secretion by blocking KATP and KV channels of beta cells, Eur J Pharmacol 2007; 568: 269–277.
Su HC, Hung LM, Chen JK. Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats, Am J Physiol Endocrinol Metab 2006; 290: 1339–1346.
Toppel G, Lei B, Fraga A (2004). Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma. Free Radic Biol Med, 2004; 18(11): 895.
Hvang IK, Kim DW, Park JH, Lim SS, Yoo KK, Kwon DY, et al. Effects of grape seed extract and its ethylacetate/ethanol fraction on blood glucose levels in a model of type 2 diabetes, Phytother Res 2009; 23(8): 1182–1185.
Majeed Dr, Khitam HM, Rashad JS, Ghadhban F. Role of grape seed extract as anti hyperglycemia and antioxidant in experimental diabetic rats, Journal of Misan Researches 2008; 4: 8.
Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine, Am J Enol Vitic1992; 43: 49–52.
Waltner-Law ME, Wang XL, Law BK, Hall RK, Nawano M, Granner DK. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production, J Biol Chem 2002; 277: 34933–34940.
Giardino I, Fard AK, Hatchell DL, Brownlee M. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation and oxidant induced apoptosis. Diabetes 1998; 47:1114-20.
Saxena AK, Srivastava P, Kale RK, Baquer NZ. Impaired antioxidant status in diabetic rat liver. Effect of vanadate. Biochem Pharmacol 1993; 45: 539-42.
Hasan K, Namık D. Gebelikte ve postpartum erken dönemde serbest radikal oluşumu ve antioksidan enzim düzeyleri. SDíœ Tıp Fakültesi Dergisi 1996; 3: 67-70.
Brüne B, von Knethen A, Sandau KB. Nitric oxide and its role in apoptosis. Eur J Pharmacol 1998; 26(351): 261-72.
Haligur M, Topsakal S, Ozmen O. Early degenerative effects of diabetes mellitus on pancreas, liver, and kidney in rats: An immunohistochemical study. Exp Diabetes Res 2012; 2012: 120645
Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes 1999; 48: 1-9
Irak K. The effects of grape seed extract on the some enzymes and metabolites in diabetic rats. YYU Institute of Health Sciences, Ph.D Thesis in Department of Biochemistry, 2014, Van.