Oxidative Stress Status in Testis of Type-2 Diabetic Rats Treated with Delta-9-Tetrahydrocannabinol

Year 2021, Volume: 80 Issue: 2, 91 - 96, 17.12.2021

Ebrar Tutar Beti Pesen Zeynep Mine Coşkun Sema Bolkent

https://doi.org/10.26650/EurJBiol.2021.1001540

Abstract

Objective: Type-2 diabetes (T2D) is a multifactorial disease that occurs as a result of impaired insulin secretion and increased glucose. Researchers emphasize that oxidative stress prevention and improvement strategies are important in the general treatment of T2D. It is reported that delta-9-tetrahydrocannabinol (THC), a component of the cannabis plant, has positive effects against oxidative stress and inflammation. Therefore, this study explored the inhibitory effects of THC on oxidative damage of testis in type-2 diabetic rats.

Materials and Methods: Adult Spraque-Dawley rats were separated into 4 groups. In the control group, physiological saline was given intraperitoneally. In the T2D model group (T2DM), streptozotocin (STZ) + nicotinamide (NAD) was administered intraperitoneally. Three mg/kg/day THC was given to the THC and T2DM+THC groups for 7 days, intraperitoneally. Glutathione (GSH), malondialdehyde (MDA), and protein carbonyl levels (PCO), and superoxide dismutase (SOD) activity were measured spectrophotometrically in testicular tissue. Total oxidant and antioxidant status were determined by ELISA.

Results: Testicular GSH level and SOD activity were significantly decreased in T2D, while MDA and PCO levels increased. In contrast to this effect, the THC treatment increased GSH levels and SOD activity in diabetics, but decreased MDA and PCO levels.

Conclusion: According to the study results, THC may have an oxidative stress inhibitory effect on diabetic rat testis.

Keywords

Diabetes, tetrahydrocannabinol, testis, oxidative stress

References

• 1. Derkach KV, Bakhtyukov AA, Bayunova LV, Zorina II, Shpakov AO. Normalization of testicular steroidogenesis and spermatogenesis in male rats with type 2 diabetes mellitus under the conditions of metformin therapy. Dokl Biol Sci 2020;493(1):110-3. google scholar
• 2. Laakso M. Biomarkers for type 2 diabetes. Mol Metab 2019;27(l):139-46. google scholar
• 3. Tian Y, Song W, Xu D, Chen X, Li X, Zhao Y. Autophagy induced by ROS aggravates testis oxidative damage in diabetes via breaking the feedforward loop linking p62 and Nrf2. Oxid Med Cell Longev 2020; 7156579. google scholar
• 4. Ranjan A, Choubey M, Yada T, Krishna A. Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice. J Endocrinol Invest 2020;43(4):515-28. google scholar
• 5. Amin MR, Ali DW. Pharmacology of medical cannabis. Adv Exp Med Biol 2019;1162:151-65. google scholar
• 6. Vella RK, Jackson DJ, Fenning AS. AMetrahydrocannabinol pre-vents cardiovascular dysfunction in STZ-diabetic Wistar-Kyoto rats. Biomed Res Int 2017; 7974149. google scholar
• 7. Coskun ZM, Bolkent S. Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats. Acta Histochem 2014;116(1):112-6. google scholar
• 8. Li X, Kaminski NE, Fischer LJ. Examination of the immunosup-pressive effect of delta9-tetrahydrocannabinol in streptozo-tocin-induced autoimmune diabetes. Int Immunopharmacol 2001;1(4):699-712. google scholar
• 9. Cantele C, Bertolino M, Bakro F, Giordano M, Jçdryczka M, Cardenia V. Antioxidant effects of hemp (Cannabis sativa L.) inflorescence ex-tract in stripped linseed oil. Antioxidants (Basel) 2020;9(11):1131. google scholar
• 10. Raja A, Ahmadi S, de Costa F, Li N, Kerman K. Attenuation of oxida-tive stress by cannabinoids and cannabis extracts in differentiated neuronal cells. Pharmaceuticals (Basel) 2020;13(11):328. google scholar
• 11. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998;47(2):224-9. google scholar
• 12. Beutler E. Glutathione: red cell metabolism. A manual of biochem-ical methods. Grune and Stratton, New York, 1975:112-4. google scholar
• 13. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzy-mol 1978; 52:302-10. google scholar
• 14. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophoto-metric method for carbonyl assay. Methods Enzymol 1994;233:357-63. google scholar
• 15. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of super-oxide dismutase. Clin Chem 1988;34:497-500. google scholar
• 16. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of pro-tein-dye binding. Anal Biochem 1976;72:248- 54. google scholar
• 17. Macho-Gonzalez A, Garcimartı'n A, Lopez-Oliva ME, Ruiz-Roso, B, Martı'n de la Torre, I, Bastida, S, et al. Can carob-fruit-extract-en-riched meat improve the lipoprotein profile, VLDL-oxidation, and LDL receptor levels induced by an atherogenic diet in STZ-NAD-di-abetic rats? Nutrients 2019;11(2):332. google scholar
• 18. Rezagholizadeh L, Pourfarjam Y, Nowrouzi A, Nakhjavani M, Mey-samie A, Ziamajidi, N, et al. Effect of Cichorium intybus L. on the expression of hepatic NF-kB and IKK0 and serum TNF-A in STZ- and STZ+Niacinamide-induced diabetes in rat. Diabetol Metab Syndr 2016; 8:11. google scholar
• 19. Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: How are they interlinked? J Cell Biochem 2017;118(11):3577-85. google scholar
• 20. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol 2019;70(6):809-24. google scholar
• 21. Oyenihi AB, Opperman M, Alabi TD, Mpahleni B, Masola B. Centella asiatica alleviates diabetes-induced changes in fatty acid profile and oxidative damage in rat testis. Andrologia 2020;52(10):e13751. google scholar
• 22. Roy VK, Chenkual L, Gurusubramanian G. Protection of testis through antioxidant action of mallotus roxburghianus in alloxan-in-duced diabetic rat model. J Ethnopharmacol 2015;176:268-80. google scholar
• 23. Thyagaraju BM, Muralidhara. Ferulic acid supplements abrogate oxidative impairments in liver and testis in the streptozotocin-dia-betic rat. Zoolog Sci 2008;25(8):854-60. google scholar
• 24. Al-Megrin WA, El-Khadragy MF, Hussein MH, Mahgoub S, Ab-del-Mohsen DM, Taha H, et al. Green Coffea arabica extract ame-liorates testicular injury in high-fat diet/streptozotocin-induced diabetes in rats. J Diabetes Res 2020;6762709. google scholar
• 25. Abdullah F, Khan Nor-Ashikin MN, Agarwal R, Kamsani YS, Abd Malek M, Bakar NS, et al. Glutathione (GSH) improves sperm qual-ity and testicular morphology in streptozotocin-induced diabetic mice. Asian J Androl 20121;23(3):281-7. google scholar
• 26. Choubey M, Ranjan A, Bora PS, Krishna A. Protective role of adi-ponectin against testicular impairment in high-fat diet/streptozo-tocin-induced type 2 diabetic mice. Biochimie 2020;168:41-52. google scholar
• 27. Ismail M, Hasan H, El-Orfali Y, Ismail H, Khawaja G. Anti-inflamma-tory, antioxidative, and hepatoprotective effects of trans A9-tetra-hydrocannabinol/sesame oil on adjuvant-induced arthritis in rats. Evid Based Complement Alternat Med 2018;9365464. google scholar
• 28. Vacek J, Vostalova J, Papouskova B, Skarupova D, Kos M, Kabelac M, et al. Antioxidant function of phytocannabinoids: molecular basis of their stability and cytoprotective properties under UV-irradia-tion. Free Radic Biol Med 2021;164:258-70. google scholar
• 29. Oliveira PF, Tomas GD, Dias TR, Martins AD, Rato L, et al. White tea consumption restores sperm quality in prediabetic rats pre-venting testicular oxidative damage. Reprod Biomed Online 2015;31(4):544-56. google scholar
• 30. Mandal TK, Das NS. Effect of delta-9-tetrahydrocannabinol on al-tered antioxidative enzyme defense mechanisms and lipid peroxi-dation in mice testes. Eur J Pharmacol 2009;607(1-3):178-87. google scholar
• 31. Borges RS, Batista JJr, Viana RB, Baetas AC, Orestes E, Andrade MA, et al. Understanding the molecular aspects of tetrahydrocannabi-nol and cannabidiol as antioxidants. Molecules 2013;18(10):12663-74. google scholar