MATERNAL AND FETAL HEPATIC INJURY IN GESTATIONAL DIABETIC RATS: PROTECTIVE ROLE OF CINNAMALDEHYDE AND ELLAGIC ACID
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i7.25126Keywords:
Diabetes, Oxidative stress, Lipid profile, Liver architecture, Hepatocytes proliferation, Natural productsAbstract
Objective: This study aims to determine the protective effect of cinnamaldehyde (Ci) and ellagic acid (EA) on maternal and fetal hepatic injury caused by fatty-sucrosed-diet/streptozotocin (FSD/STZ)-rat model of gestational diabetes (GD).
Methods: Female Wistar rats were allocated into four groups. Group I fed with a normal diet, while Groups II, III, and IV feds with FSD for 8 weeks (five pre-gestational and three gestational). One week before mating onward, Group III and IV administered daily oral dose of 20 mg/kg Ci or 50 mg/kg EA, respectively. At the 7th day of gestation, FSD-fed groups injected intraperitoneally with STZ (25 mg/kg b.wt.) to induce GD mellitus. At the end of gestation, maternal and fetal blood, pancreas and liver samples were taken for the subsequent analysis.
Results: Ci and EA potentially protect from the elevated glucose, triglycerides, total cholesterols, liver transaminases, and the depleted serum insulin, high-density lipoprotein-cholesterol, total proteins and albumin of GD-rats. As well, tested agents alleviated the altered fetal glucose and insulin levels. Alongside, Ci and EA reduced the maternal and fetal liver lipid peroxidation and increased their total thiols and total peroxidases. Furthermore, Ci and EA kept the normal intact of maternal and fetal pancreatic islets and preserve their livers away from the pathological changes observed in GD group that included fatty depositions, inflammation, hepatocytic necrosis and fibrosis, congested veins, diminutive storable glycogen and proteins, and the numerous proliferating cell nuclear antigen nuclei.
Conclusion: Ci and EA have potent hepatoprotective effects through their insulin-sensitizing action and activating the antioxidant defenses.
Downloads
References
International Diabetes Federation. Diabetes Atlas. 7th ed. Brussels, Belgium: IDF; 2015.
Muhas C, Naseef PP. A review article-gestational diabetes mellitus. Int J Curr Pharm Res 2017;9:1-5.
Hod M, Jovanovic LG, Di-Renzo GC, De-Leiva A, Langer O. Textbook of Diabetes and Pregnancy. 3rd ed. London: Informa Health Care; 2008.
Ajmera VH, Gunderson EP, VanWagner LB, Lewis CE, Carr JJ, Terrault NA, et al. Gestational diabetes mellitus is strongly associated with non-alcoholic fatty liver disease. Am J Gastroenterol 2016;111:658- 64.
Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace. J Hepatol 2012;56:1384-91.
Magon N, Seshiah V. Gestational diabetes mellitus: Non-insulin management. Indian J Endocrinol Metab 2011;15:284-93.
El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004;126:460-8.
Subash-Babu P, Alshatwi AA, Ignacimuthu S. Beneficial antioxidative and antiperoxidative effect of cinnamaldehyde protect streptozotocin-induced pancreatic β-cells damage in wistar rats. Biomol Ther 2014;22:47-54.
Subash Babu P, Prabuseenivasan S, Ignacimuthu S. Cinnamaldehyde–a potential antidiabetic agent. Phytomedicine 2007;14:15-22.
Malini P, Kanchana G, Rajadurai M. Antidiabetic efficacy of ellagic acid in streptozotocin-induced diabetes mellitus in albino wistar rats. Asian J Pharm Clin Res 2011;4:124-28.
Sepúlveda L, Ascacio A, RodrÃguez-Herrera R, Aguilera-Carbó A, Aguilar CN. Ellagic acid: Biological properties and biotechnological development for production processes. Afr J Biotechnol 2011;10:4518-23.
Abu El-Soud W, Hegab MM, AbdElgawad H, Zinta G, Asard H. Ability of ellagic acid to alleviate osmotic stress on chickpea seedlings. Plant Physiol Biochem 2013;71:173-83.
Abdel-Reheim ES, Abd-Elmoneim A, Hosni AA. Fatty-Sucrosed diet/ minimal dose of streptozotocin-treated rat: A novel model of gestational diabetes mellitus, metabolic and inflammatory insight. J Diabetes Metab 2014;5:430.
Yagi K. Lipid peroxides and human diseases. Chem Phys Lipids 1987;45:337-51.
Koster JF, Bieermond P, Swaak AJ. Intracellular and extracellular sulfhydryl levels in rheumatoid arthritis. Ann Rheu Dis 1986;45:44-6.
Kar M, Mishra D. Catalase, peroxidase and polyphenoloxidase activities during rice leaf senescence. Plant Physiol 1976;57:315-9.
Bancroft JD, Stevens A. Theory and Practice of Histological Techniques. 2nd ed. London: Chruchill Livingstone Elsevier; 1982.
Gamble M. The hematoxylins and eosin. In: Bancroft JD, Stevens A, editors. Theory and Practice of Histological Techniques. 6th ed. London, UK: Chruchill Livingstone; 2008. p. 121-34.
Myers RB, Fredenburgh JL, Grizzle WE. Carbohydrates. In: Bancroft JD, Stevens A, editors. Theory and Practice of Histological Techniques. 6th ed. London, UK: Chruchill Liveingstone; 2008. p. 161- 86.
Mazia D, Brewer P. Cytochemical staining and measurement of protein with mercuric bromophenol blue. Biol Bull 1953;104:57-67.
Bhan A. Immunoperoxidase in Diagnostic Immunopathology. 2nd ed. New York: Raven Press Ltd.; 1995.
Zhang F, Ye C, Li G, Ding W, Zhou W, Zhu H, et al. The rat model of Type 2 diabetic mellitus and its glycometabolism characters. Exp Anim 2003;52:401-7.
Lenzen S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia 2008;51:216-26.
Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 2004;25:612-28.
Arulselvan P, Subramanian SP. Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultrastructural changes of pancreatic β-cells in experimental diabetes in rats. Chem Biol Interact 2007;165:155-64.
Devipriya N, Srinivasan M, Sudheer AR, Menon VP. Effect of ellagic acid, a natural polyphenol, on alcohol-induced prooxidant and antioxidant imbalance: A drug dose dependent study. Singapore Med J 2007;48:311-8.
Balcerczyk A, Bartosz G. Thiols are main determinants of total antioxidant capacity of cellular homogenates. Free Radic Res 2003;37:537-41.
Kale MA, Bindu SM, Khadkikar P. Role of antioxidants and nutrition in oxidative stress: A review. Int J App Pharm 2015;7:1-4.
Gokce G, Haznedaroglu MZ. Evaluation of antidiabetic, antioxidant and vasoprotective effects of Posidonia oceanica extract. J Ethnopharmacol 2008;115:122-30.
Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: Insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab Res Rev 2005;21:3-14.
Bhasy B, Varghese L, Krishnan A, Viswanath L. Perceived risk and abilities for health practices related to prevention of Type II diabetes mellitus among postnatal mothers with gestational diabetes mellitus. Asian J Pharm Clin Res 2018;11:354-6.
Singh AK, Chawla V, Saraf SK, Keshari AK. Different chemical, biological and molecular approaches for anti-hyperlipidemic therapy with special emphasis on anti-hyperlipidemic agents of natural origin. J Crit Rev 2014;1:1-9.
Elizabeth H, Harris MD. Elevated liver function tests in Type 2 diabetes. Clin Diabetes 2005;23:115-9.
Navarro CM, Montilla PM, Martin A, Jimenez J, Utrilla PM. Free radicals scavenger and antihepatotoxic activity of rosmarinus. Plant Med 1993;59:312-4.
William W, Hay J. Nutrient delivery and metabolism in the fetus. In: Hod M, Jovanovic L, Di Renzo GC, de Leiva A, Langer O, editors. Textbook of Diabetes and Pregnancy. 2nd ed. London, UK: Informa UK Ltd.; 2008. p. 57-70.
Møller N, Nair KS. Diabetes and protein metabolism. Diabetes 2008;57:3-4.
Crawford JM, Iacobuzio-Donahue C. Liver and biliary tract. In: Kumar V, Abbas AK, Fausto N, Aster JC, Robbins ED, Cotran A. Pathologic Basis of Disease. 8th ed. Philadelphia, Pennsylvania, USA: Saunders; 2009.
Richardson A, Fulton C, Catlow D, Carpenter M, Sharma S. Cytokine profiles in pregnant women with gestational diabetes mellitus. Am J Obstet Gynecol 2006;195:163.
Balistreri WF, Rej R. Liver function. In: Burtis CA, Ashwood ER, Aldrich JE, editors. Tietz Fundamental of Clinical Chemistry. 4th ed. Philadelphia: WB Saunders Company; 1996.
Manna P, Das J, Ghosh J, Sil PC. Contribution of Type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PPAR, IκBα/ NF-κB, MAPKs, and mitochondria-dependent pathway: Prophylactic role of arjunolic acid. Free Radic Biol Med 2010;48:1465-84.
Holliman JH. Principles of cell/tissue injury. In: Pathology, Oklahoma Notes. New York: Springer; 1995.
Vats V, Yadav SP, Grover JK. Ethanolic extract of Ocimum sanctum leaves partially attenuates streptozotocin-induced alterations in glycogen content and carbohydrate metabolism in rats. J Ethnopharmacol 2004;90:155-60.
Shiina H, Igawa M, Nagami H, Yagi H, Urakami S, Yoneda T, et al. Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder. Cancer 1996;78:1762-74.
Day PE, Cleal JK, Lofthouse EM, Hanson MA, Lewis RM. What factors determine placental glucose transfer kinetics? Placenta 2013;34:953-8.
Holemans K, Aerts L, Van Assche FA. Lifetime consequences of abnormal fetal pancreatic development. J Physiol 2003;547:11-20.
Hokke SN, Armitage JA, Puelles VG, Short KM, Jones L, Smyth IM, et al. Altered ureteric branching morphogenesis and nephron endowment in offspring of diabetic and insulin-treated pregnancy. PLoS One 2013;8:e58243.
Ahmed OM, Aref AM, Semmler M, Ali LA. Maternal diabetes mellitus disturbs histological architecture and integrity of liver and kidney in rat offspring. Merit Res J Med Med Sci 2015;3:335-46.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
