Pancreas-protective effects of chlorella in STZ-induced diabetic animal model: insights into the mechanism

Amr Amin, Mohamed Lotfy, Doaa Mahmoud-Ghoneim, Ernest Adeghate, Mohamed A. Al-Akhras, Maryam Al-Saadi, Salam Al-Rahmoun, Rasheed Hameed

.

DOI: 10.4236/jdm.2011.13006                

Abstract

The aim of this study is to examine the effect of intragastric administration of chlorella (1 g/kg body weight) for a period of 30 days to treat normal and diabetic male Wistar rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg - 1 body weight). A significant (p < 0.05) reduction of blood glucose level in diabetic chlorella-treated rats was observed compared to diabetic untreated. Chlorella increased the number of glutathione-positive cell in diabetic rats compared to untreated diabetics. Chlorella administration increased the percentage of insulin secreting pancreatic beta cells both in normal and diabetic treated rats. Percentage of glucagon producing alpha cells of the pancreas were reduced both in normal and diabetic chlorella-treated rats. Chlorella-induced regenerative ability on pancreas was mediated by up-regulation of Ki67 and down-regulation of P53 and by its potent anti-oxidant ability. The present results suggest that chlorella may play an important role in improving the overall condition of diabetic patients and delay its complication by restoring the function of pancreatic insulin-secreting cells.

Keywords

Chlorella; Diabetes; Glucose; Insulin; Beta Cells.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Zhou, J., Zhou, S., Tang, J., Zhang, K., Guang, L., Huang, Y., Xu, Y., Ying, Y., Zhang, L. and Li, D. (2009) Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. European Journal of Pharmacology, 606, 262-268. doi:10.1016/j.ejphar.2008.12.056
[2]	Punithavathi, V.R., Prince, P.S.M., Kumar, R. and Selvakumari, J. (2011) Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin-induced diabetic Wistar rats. European Journal of Pharmacology, 650, 465-471. doi:10.1016/j.ejphar.2010.08.059
[3]	Jin, L., Xue, H.-Y., Jin, L.-J., Li, S.-Y. and Xu, Y.-P. (2008) Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes. European Journal of Pharmacology, 582, 162-167. doi:10.1016/j.ejphar.2007.12.011
[4]	Frode, T.S. and Medeiros, Y.S. (2008) Animal models to test drugs with potential antidiabetic activity. Journal of Ethnopharmacology, 115, 173-183. doi:10.1016/j.jep.2007.10.038
[5]	Baynes, J.W. and Thorpe, S.R. (1996) The role of oxidative stress in diabetic complications. Current Opinion of Endocrinology, 3, 277-284. doi:10.1097/00060793-199608000-00001
[6]	Ihara, Y., Toyokuni, S., Uchida, K., Odaka, H., Tanaka, T., Ikeda, H., Hiai, H., Seino, Y. and Yamada, Y. (1999) Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats a model of type 2 diabetes. Diabetes, 48, 927-932. doi:10.2337/diabetes.48.4.927
[7]	Saxena, A.K., Srivastava, P., Kale, R.K. and Baquer, N.Z. (1993) Impaired antioxidant status in diabetic rat liver. Effect of vanadate. Biochemical Pharmacology, 45, 539-542. doi:10.1016/0006-2952(93)90124-F
[8]	Maritim, A.C., Sanders, R.A. and Watkins, J.B. (2003) Effect of alpha lipoic acid on biomarkers of oxidative stress in streptozotoc in-induced diabetic rats. The Journal of Nutritional Biochemistry, 14, 288-294. doi:10.1016/S0955-2863(03)00036-6
[9]	Ames, B.N. (1989) Endogenous oxidative DNA damage, aging, and cancer. Free Radical Research Communication, 7, 121-128. doi:10.3109/10715768909087933
[10]	Ku, Y.P., Jin, M., Kim, K.H., Ahn, Y.J., Yoon, S.P., You, H.J. and Chang, I.Y. (2009) Immunolocalization of 8-OHdG and OGG1 in pancreatic islets of streptozotocin-induced diabetic rats. Acta Histochemica, 111, 138-144. doi:10.1016/j.acthis.2008.05.008
[11]	Mythili, M.D., Vyas, R., Akila, G. and Gunasekaran, S. (2004). Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microscopy Research and Technique, 63, 274-281. doi:10.1002/jemt.20039
[12]	Jagtap, U.B. and Bapat, V.A. (2010) Artocarpus: A review of its traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology, 129, 142-166. doi:10.1016/j.jep.2010.03.031
[13]	Lee, H.S., Choi, C.Y., Cho, C. and Song, Y. (2003) Attenuating effect of Chlorella supplement on oxidative stress and NF-kB activation in peritoneal macrophage and liver of C57BL/6 mice fed on an atherogenic diet. Bioscience biotechnology and biochemistry, 67, 2083-2090. doi:10.1271/bbb.67.2083
[14]	Guzman, S., Gato, A. and Calleja, J.M. (2001) Anti-imflammatory activities of the marine microalgae. Chlorella Stigmatophora and Phaeodactylum tricornutum. Phytotherapy Research, 15, 224-230. doi:10.1002/ptr.715
[15]	Amin, A. (2008) Chemopreventive effect of chlorella on the antioxidant system in DMBA-induced oxidative stress in liver. International Journal of Pharmacology, 4, 169-176. doi:10.3923/ijp.2008.169.176
[16]	Amin, A. (2009) Protective effect of green algae against 7,12-dimethylbenzanthrancene (DMBA)-induced breast cancer in rats. International Journal of Cancer Research, 5, 12-24. doi:10.3923/ijcr.2009.12.24
[17]	Cherng, J.-Y. and Shih, M.-F. (2005) Potential hypoglycemic effects of Chlorella in streptozotocin-induced diabetic mice. Life Sciences, 77, 980-990. doi:10.1016/j.lfs.2004.12.036
[18]	Cherng, J.-Y. and Shih, M.-F. (2006) Improving glycogenesis in Streptozocin (STZ) diabetic mice after administration of green algae Chlorella. Life Sciences, 78, 1181-1186. doi:10.1016/j.lfs.2005.06.050
[19]	Adeghate, E. (1999) Effect of subcutaneous pancreatic tissue transplants on streptozotocin-induced diabetes in rats. I. Morphological studies on normal, diabetic and transplanted pancreatic tissues. Tissue and Cell, 31, 66- 72. doi:10.1054/tice.1999.0008
[20]	Caluwaerts, S., Lambin, S., van Bree, R., Peeters, H., Vergote, I. and Verhaeghe, J. (2007) Diet-induced obesity in gravid rats engenders early hyperadiposity in the offspring. Metabolism, 56, 1431-1438. doi:10.1016/j.metabol.2007.06.007
[21]	Sharma, B., Balomajumder, C. and Roy, P. (2008) Hypoglycemic and hypolipidemic effects of flavonoid rich extract from Eugenia jambolana seeds on streptozotocin induced diabetic rats. Food and Chemical Toxicology, 46, 2376-2383. doi:10.1016/j.fct.2008.03.020
[22]	Salazar-Montes, A., Ruiz-Corro, L., López-Reyes, A., Castrejón-Gómez, E. and Armendáriz-Borunda, J. (2008) Potent antioxidant role of pirfenidone in experimental cirrhosis. European Journal of Pharmacology, 595, 69-77. doi:10.1016/j.ejphar.2008.06.110
[23]	Upadhyay, O.P., Singh, R.M. and Dutta, K. (1996) Studies on antidiabetic medicinal plants used in Indian folk-lore. Aryavaidyan, 9, 159-167.
[24]	Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010) Oxidative stress, inflammation, and cancer: How are they linker? Free Radical Biology and Medicine, 49, 1603-1616. doi:10.1016/j.freeradbiomed.2010.09.006
[25]	Picton, S.F., Flatt, P.R. and Mcclenghan, N.H. (2001) Differential acute and long term actions of succinic acid monomethyl ester exposure on insulin secreting BRAIN-BD 11 cells. International Journal of Experimental Diabetes Research, 2, 19-27. doi:10.1155/EDR.2001.19
[26]	Grover, J.K., Vats, V. and Rathi, S.S. (2000) Anti-hyperglycemic effect of Eugenia jambolana and Tinospora cordifolia in experimental diabetes and their effects on key metabolic enzymes involved in carbohydrate metabolism. Journal of Ethnopharmacology, 73, 461-470. doi:10.1016/S0378-8741(00)00319-6
[27]	Leng, S.H., Lu, F.E. and Xu, L.J. (2004) Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacologica Sinica, 25, 496-502.
[28]	K?hler, C.U., Kreuter, A., Rozynkowski, M.C., Rahmel, T., Uhl, W., Tannapfel, A., Schmidt, W.E. and Meier, J.J. (2010) Validation of different replication markers for the detection of beta-cell proliferation in human pancreatic tissue. Regulatory Peptides, 162, 115-121. doi:10.1016/j.regpep.2009.12.021
[29]	Shohet, J.M., Hicks, M.J., Plon, S.E., Burlingame, S.M., Stuart, S., Chen, S.Y., Brenner, M.K. and Nuchtern, J.G. (2002) Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Research, 62, 1123-1128.
[30]	Jaskulski, D., deRiel, J.K., Mercer, W.E., Calabretta, B. and Baserga, R. (1988) Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. Science, 240, 1544-1546. doi:10.1126/science.2897717
[31]	Bruno, S., Crissman, H.A., Bauer, K.D. and Darzyn- kiewicz, Z. (1991) Changes in cell nuclei during S phase: Progressive chromatin condensation and altered expression of the proliferation-associated nuclear proteins Ki-67, cyclin [PCNA], p105 and p34. Experimental Cell Research, 196, 99-106. doi:10.1016/0014-4827(91)90460-C
[32]	Tsurusawa, M., Ito, M., Zha, Z., Kawai, S., Takasaki, Y. and Fujimoto, T. (1992) Cell-cycle associated expressions of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia. Leukemia, 6, 669-674.
[33]	Kahn, S.E. (2003) The relative contributions of insulin resistance and β-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia, 46, 3-19.
[34]	Rashid, M.A., Lee, S., Tak, E., Lee, J., Choi, T.J., Lee, J.-W., Kim, J.B., Youn, J.H., Kang, I., Ha, J. and Kim, S.S. (2010) Carbonyl reductase 1 protects pancreatic β-cells against oxidative stress-induced apoptosis in glucotoxicity and glucolipotoxicity. Free Radical Biology and Medicine, 49, 1522-1533. doi:10.1016/j.freeradbiomed.2010.08.015