Evaluation of P53 and Nrf2 protein levels in kidney tissue after 8 weeks of endurance training in diabetic rats with morphine withdrawal syndrome

authors:

avatar Azadbakht Azadbakht , avatar Abbas Saremi ORCID , * , avatar Mojtaba khansooz ORCID


how to cite: Azadbakht A, Saremi A, khansooz M . Evaluation of P53 and Nrf2 protein levels in kidney tissue after 8 weeks of endurance training in diabetic rats with morphine withdrawal syndrome. koomesh. 2023;25(6):e152863. 

Abstract

Introduction: P53 protein is one of the factors regulating apoptosis and Nrf2 is the main regulator of antioxidant proteins. This study aimed to evaluate P53 and Nrf2 protein levels in kidney tissue after 8 weeks of endurance training in diabetic rats with morphine withdrawal syndrome. Materials and Methods: In this experimental study, 32 Wistar rats were used, which were randomly divided into 4 groups of 8. After inducing diabetes and creating dependence on morphine by oral method, the training groups performed an endurance training protocol for 8 weeks. The groups included: diabetes (D), morphine diabetes (D.M), diabetes+ endurance training (D.ET), and morphine diabetes+ endurance training (D.M.ET). On the last day of the study, all rats were killed and their kidneys were removed. The protein levels of the indicators of this study were measured by ELISA kits. Results: The results of this study showed that the P53 protein level in the D.ET training group (P=0.000) compared to the D group and the D.M.ET training group (P=0.002) compared to the D.M. group, has a significant decrease. It was also observed that the Nrf2 protein level increased significantly in the D.ET (P=0.020) and D.M.ET (P=0.009) training groups compared to the D group. Conclusion: Endurance training by increasing Nrf2 probably strengthens the antioxidant system and reduces oxidative stress. By reducing p53, it reduces the apoptosis of kidney tissue in diabetic and diabetic rats with morphine withdrawal syndrome.

References

  • 1.

    Karimi MN, Abbasalipourkabir R, Arab Sadeghabadi Z, Ziamajidi N. The level of gene expression of Bax and Bcl-2 and the activity of caspase 3 in the liver tissues of normal, type 1 and type 2 diabetic rats before and after treatment with aqueous extract of garlic. J Shahid Sadoughi Univ Med Sci 2017; 7: 547-555. (Persian).

  • 2.

    Seyedi ZS. Oxidative stress and human diseases: a review. Iran J Biol 2022; 10: 134-141.

  • 3.

    Negi CK, Jena G. Nrf2, a novel molecular target to reduce type 1 diabetes associated secondary complications: The basic considerations. Eur J Pharmacol 2019; 843: 12-26.

  • 4.

    Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 2003; 1: 233-260.

  • 5.

    Jimnez-Osorio AS, Picazo A, Gonzlez-Reyes S, Barrera-Oviedo D, Rodrguez-Arellano ME, Pedraza-Chaverri J. Nrf2 and redox status in prediabetic and diabetic patients. Int J Mol Sci 2014; 11: 20290-20305.

  • 6.

    Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis - the p53 network. J Cell Sci 2003; 20: 4077-4085.

  • 7.

    Asadikaram G, Asiabanha M, Sirati Sabet M. Ovary cells apoptosis in opium-addicted diabetic and non-diabetic rats. Int J High Risk Behav Addict 2013; 1: 3-7.

  • 8.

    Singh VK, Bajpai K, Biswas S, Haq W, Khan MY, Ma- thur KB. Molecular biology of opioid receptors: recent advances. Neuroimmunomodulation 1997; 5-6: 285-297.

  • 9.

    Lux F, Brase DA, Dewey WL. Differential effects of subcutaneous and intrathecal morphine administration on blood glucose in mice: comparison with intrace- rebroventricular administration. J Pharmacol Exp Ther 1988; 1: 187-194.

  • 10.

    Mirzaei A, Zendehdel K, Rashidian H, Aghaii M, Ghahestani SM, Roudgari H. The impact of OPIUM and its derivatives on cell apoptosis and angiogenesis. Translat Res Urol 2020; 4: 110-117.

  • 11.

    Singhal PC, Sharma P, Kapasi AA, Reddy K, Franki N, Gibbons N. Morphine enhances macrophage apoptosis. J Immunol 1998; 4: 1886-1893.##https://doi.org/10.4049/jimmunol.160.4.1886.

  • 12.

    Reymond S, Vuji T, Schvartz D, Sanchez JC. Morphine-induced modulation of Nrf2-antioxidant response element signaling pathway in primary human brain microvascular endothelial cells. Sci Rep 2022; 1: 4588.

  • 13.

    Negharestani HR, Hosseinpour S, Azizi M, Azarbaijani M A, Farzanegi P. The effect of combination of regular continuous exercise and resveratrol supplementation on some regulatory and executive factors of hepatocytic apoptosis in male diabetic rats. Feyz 2019; 6: 605-614.

  • 14.

    Abbasi E, Salehi I, Zarin Kalam E, Ranjbar K. Mirzaei F, Komaki AR, et al. Protective effect of exercise on liver oxidative stress, inflammation and histopathological changes after morphine withdrawal in rats. J Mazandaran Univ Med Sci 2022; 207: 26-37. (Persian).

  • 15.

    Punitha IS, Rajendran K, Shirwaikar A. Alcoholic stem extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. Evid Based Complement Alternat Med 2005; 3: 375-381.

  • 16.

    Jalalvand A, Heidarianpour A, Almasi J. Acute effects of swimming exercise on withdrawal syndrome sign in morphine-dependent rats. Sabzevar Univ Med Sci 2013; 3: 373-379. (Persian).

  • 17.

    Salmanzadeh F, Fathollahi Y, Semnanian S, Shafizadeh M, Kazemnejad A. Dependence on morphine leads to a prominent sharing among the different mechanisms of long-term potentiation in the CA1 region of rat hippocampus. Brain Res 2003; 1-2: 93-100.

  • 18.

    Yousefi MR, Taheri-chadorneshin H. The effect of moderate endurance training on gastrocnemius retinol-binding protein 4 and insulin resistance in streptozotocin-induced diabetic rats. Interv Med Appl Sci 2018; 1: 59-63.

  • 19.

    Wagener FA, Dekker D, Berden JH, Scharstuhl A, van der Vlag J. The role of reactive oxygen species in apoptosis of the diabetic kidney. Apoptosis 2009; 12: 1451-1458.

  • 20.

    Quan S, Kaminski PM, Yang LM, Morita T, Inaba M, Ikehara S, et al . Heme oxygenase-1 prevents superoxide anion-associated endothelial cell sloughing in diabetic rats. Biochem Biophys Res Commun 2004; 2: 509-516.

  • 21.

    Sharafi H, Rahimi R. The effect of resistance exercise on p53, caspase-9, and caspase-3 in trained and untrained men. J Strength Cond Res 2012; 4: 1142-1148.

  • 22.

    Seyedgomi F, Bashiri J, Gholami F. Effect of high intensity endurance training on p53 and cytochrome-c gene expression in male rat soleus muscle. Armaghane-danesh 2017; 5: 608-622. (Persian).

  • 23.

    Sha J, Sui B, Su X, Meng Q. Zhang CH. Alteration of oxidative stress and inflammatory cytokines induces apoptosis in diabetic nephropathy. Mol Med Rep 2017; 16: 7715-7723.

  • 24.

    Qi Z, He J, Zhang Y, Shao Y, Ding S. Exercise training atenuates oxidatve stress and decreases p53 protein content in skeletal muscle of type 2 diabetc Goto-Kakizaki rats. Free Radic Biol Med 2011; 7: 794-800.

  • 25.

    Jokar M, Sherafati Moghadam M. Effect of 4 weeks of high-intensity interval training on P53 and Caspase-3 proteins content in the heart muscle tissue of rats with type 1 diabetes. J Shahid Sadoughi Uni Med Sci 2022; 1: 4255-4267. (Persian)##https://doi.org/10.18502/ssu.v29i11.8502.

  • 26.

    Sun J, Fu J, Li L, Chen C, Wang H, Hou Y, et al. Nrf2 in alcoholic liver disease. Toxicol Appl Pharmacol 2018; 357: 62-69.

  • 27.

    Cuadrado A, Pajares M, Benito C, Jimnez-Villegas J, Escoll M, Fernndez-Gins R, et al. Can activation of NRF2 be a strategy against COVID-19? Trends Pharmacol Sci 2020; 9: 598-610.

  • 28.

    McCord JM, Hybertson BM, Cota-Gomez A, Geraci KP, Gao B. Nrf2 activator PB125 as a potential therapeutic agent against COVID-19. Antioxidants 2020; 6: 518.

  • 29.

    Nadi Z, Abbasi Y, Jalali Mashayekhi F, Bayat M, Bayat P, Baazm M. Correction to: effect of resistance and endurance trainings on Nrf2/Keap1 signaling pathway in testicular tissue of type 2 diabetic rats. J Mazandaran Univ Med Sci 2023; 216: 194-195. (Persian).

  • 30.

    Farajtabar Z, Fathi R, Nasiri Kh, Ahmadi F. The effect of aerobic exercise and ethanol consumption on Nrf2 gene expression in heart tissue and some antioxidant indices in Male rat. Sport Physiol 2021; 49: 65-88.

  • 31.

    Crilly MJ, Tryon LD, Erlich AT, Hood DA. The role of Nrf2 in skeletal muscle contractile and mitochondrial function. J Appl Phys 2016; 3: 730-740.

  • 32.

    Abbasi S, Avandi S M, Haghshenas R. The effect of eight weeks Concurrent training on plasma levels of NRF2 in young men. J Appl Health Stud Sport Phys 2018; 2: 78-83.

  • 33.

    Salehi I, Zarrinkalam E, Mirzaei F, Abasi Oshaghi E, Ranjbar K, Soleimani asl S. Effects of resistance, endurance, and concurrent exercise on oxidative stress markers and the histological changes of intestine after morphine withdrawal in rats. Avicenna J Med Biochem 2018; 2: 44-49.##https://doi.org/10.15171/ajmb.2018.10.

  • 34.

    McLellan AT. Have we evaluated addiction treatment correctly? Implications from a chronic care perspective. Addiction 2002; 3: 249-252.