Antidiabetic effects of the heat-killed Actinomycetales species in the liver and kidney of diabetic rats

Document Type : Research Article


1 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Center for Infectious Diseases and International Health, Windeyer Institute for Medical Sciences, University College London, UK.


Type 1 diabetes mellitus (T1DM) occurs due to the decrease in insulin secretion following the destruction of pancreatic beta cells. This disease is increasing worldwide, especially among children under the age of 5 years, which is usually associated with irreversible complications such as hepatopathy and nephropathy. The present study aimed to investigate the antidiabetic effect of the heat-killed Actinomycetales species, including Gordonia bronchialis (Gb), and Tsukamurella inchonensis (Ti) in streptozotocin-diabetic rats by oral administration. This experiment was performed in six groups, including healthy control, diabetic control, low-dose Gb (G1), high-dose Gb (G2), low-dose-Ti (T1), and high-dose Ti (T2). Subsequently; the levels of ALT, AST, total protein, albumin, BUN, creatinine, CRP, IL-1β, and IL-2 were measured in the serum samples in the 14th and 21st days. Besides, histopathological lesions were studied in the liver and kidney. Our findings showed that Gb and Ti could alter the examined serum parameters, particularly in the T2 groups. Also, histological examination revealed a remarkable attenuation in the pathological lesions such as focal necrosis, vascular congestion, and hemorrhage in the liver and kidney of the treated rats by Gb and Ti. Here, it is concluded that oral administration of the heat-killed Actinomycetales species, particularly with a high dose of Ti, could beneficially improve the progression of T1DM and its various complications, which can be used to treat T1DM in the future.  


Main Subjects

1. Dogan Y, Akarsu S, Ustundag B, Yilmaz E, Gurgoze MK. Serum IL-1β, IL-2, and IL-6 in insulin-dependent diabetic children. Mediators of inflammation. 2006;2006. Doi:10.1155/MI/2006/59206
2. Russell MA, Morgan N. The impact of anti-inflammatory cytokines on the pancreatic β-cell. Islets. 2014;6(3):e950547. Doi:10.4161/19382014.2014.950547
3. Blake R, Trounce IA. Mitochondrial dysfunction and complications associated with diabetes. Biochimica et Biophysica Acta (BBA)-General Subjects. 2014;1840(4):1404-12. Doi:10.1016/j.bbagen.2013.11.007
4. Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World journal of diabetes. 2015;6(1):92. Doi:10.4239/wjd.v6.i1.92
5. Samadi N, Allahyari I, Zamanzadeh V, Dadkhah B, Mohammadi M. Educational Points for Prevention of Type 1 Diabetes and its Complications: A Systematic Review. J Clin Cell Immunol S. 2012;2:2.
6. Derosa G, Cicero AE, Bertone G, Piccinni MN, Ciccarelli L, Roggeri DE. Comparison of fluvastatin+ fenofibrate combination therapyand fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial. Clinical therapeutics. 2004;26(10):1599-607.
7. Hansrani M, Stanford J, McIntyre G, Bottasso O, Stansby G. Immunotherapy for the prevention of myointimal hyperplasia after experimental balloon injury of the rat carotid artery. Angiology. 2010;61(5):437-42. Doi:10.1177/0003319710366128
8. Tarrés MC, Gayol MdC, Picena JC, Alet N, Bottasso O, McIntyre G, et al. Beneficial effects of immunotherapy with extracts derived from Actinomycetales on rats with spontaneous obesity and diabetes. Immunotherapy. 2012;4(5):487-97. Doi:10.2217/imt.12.37
9. Khordadmehr M, Ghaderi S, Mesgari-Abbasi M, Jigari-Asl F, Nofouzi K, Tayefi-Nasrabadi H, et al. The Beneficial Effects of Actinomycetales Immune Modulators in the Pancreas of Diabetic Rats. Advanced Pharmaceutical Bulletin. 2021;11(2):371. Doi:10.34172/apb.2021.035
10. Khordadmehr M, Ghaderi S, Abbasi MM, Nofouzi K, McIntyre G. The improvement effects of Gordonia bronchialis on male fertility of rats with diabetes mellitus induced by streptozotocin. Pharmaceutical Sciences. 2019;25(3):227-34.
11. Mesgari-Abbasi M, Ghaderi S, Khordadmehr M, Nofouzi K, Tayefi-Nasrabadi H, McIntyre G. Enteroprotective effect of Tsukamurella inchonensis on streptozotocin induced type 1 diabetic rats. Turkish Journal of Biochemistry. 2019;44(5):683-91.
12. Hassanalilou T, Payahoo L, Shahabi P, Abbasi MM, Jafar-abadi MA, Bishak YK, et al. The protective effects of Morus nigra L. leaves on the kidney function tests and histological structures in streptozotocin-induced diabetic rats. Biomed Res. 2017;28(14):6113-8.
13. Zafar M, Naqvi SN-u-H, Ahmed M, Kaimkhani ZA. Altered Liver Morphology and Enzymes in Streptozotocin Induced Diabetic Rats. International journal of morphology. 2009;27(3).
14. Arkkila PE, Koskinen PJ, Kantola IM, Rönnemaa T, Seppänen E, Viikari JS. Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes. Diabetes Research and Clinical Practice. 2001;52(2):113-8. Doi:10.1016/s0168-8227(00)00241-2
15. Edet E, Atangwho I, Akpanabiatu M, Edet T, Uboh F, David-Oku E. Effect of Gongronema latifolium leaf extract on some liver enzymes and protein levels in diabetic and non diabetic rats. J Pharm Biomed Sci. 2011;1(5):104-7. 
16. Özer G, Teker Ζ, Cetiner S, Yılmaz M, Topaloglu AK, Önenli-Mungan N, et al. Serum IL-1, IL-2, TNFα and INFγ levels of patients with type 1 diabetes mellitus and their siblings. Journal of Pediatric Endocrinology and Metabolism. 2003;16(2):203-10.
17. Tomoda T, Kurashige T, Taniguchi T. Imbalance of the interleukin 2 system in children with IDDM. Diabetologia. 1994;37:476-82. Doi:10.1007/s001250050135
18. Wagner R, Bonifacio E, Bingley P, Genovese S, Reinwein D, Bottazzo G. Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes. The clinical investigator. 1994;72:494-8. Doi:10.1007/BF00207476
19. Karlsson Faresjö M, Ernerudh J, Ludvigsson J. Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes. Scandinavian journal of immunology. 2004;59(5):517-26. Doi:10.1111/j.0300-9475.2004.01420.x
20. Abbas MA, Abraham D, Kushner JP, McClain DA. Anti‐obesity and pro‐diabetic effects of hemochromatosis. Obesity. 2014;22(10):2120-2. Doi:10.1002/oby.20839
21. Davì G, Chiarelli F, Santilli F, Pomilio M, Vigneri S, Falco A, et al. Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration. Circulation. 2003;107(25):3199-203. Doi:10.1161/01.CIR.0000074205.17807.D0
22. Erbağci AB, Tarakçioğlu M, Coşkun Y, Sivasli E, Namiduru ES. Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children. Clinical biochemistry. 2001;34(8):645-50. Doi:10.1016/s0009-9120(01)00275-2
23. Khattab MH, Shahwan MJ, Hassan NAGM, Jairoun AA. Abnormal High-sensitivity C-reactive Protein is Associated with an Increased Risk of Cardiovascular Disease and Renal Dysfunction among Patients Diagnosed with Type 2 Diabetes Mellitus in Palestine. Review of Diabetic Studies. 2022;18(1):27-33.
24. Tietz NW. Clinical guide to laboratory tests.  Clinical guide to laboratory tests1995. p. 1096-.
25. Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman J, Smith JA, et al. Short protocols in molecular biology. New York. 1992;275:28764-73.
26. Klopfleisch R. Multiparametric and semiquantitative scoring systems for the evaluation of mouse model histopathology-a systematic review. BMC veterinary research. 2013;9:1-15. Doi:10.1186/1746-6148-9-123