Sex-dependent effects of resveratrol and regular exercise on markers related to cellular stress in the hearts and kidneys of rats

Yıl 2022, , 20 - 30, 28.04.2022

Nur Banu Bal , Sevtap Han , Suzan Usanmaz Orhan Uludağ , Emine Demirel Yılmaz

https://doi.org/10.26650/IstanbulJPharm.2022.979195

Öz

Background and Aims: Regular exercise and several food supplements are recommended for a healthy lifestyle. In this study,the sex-dependent effects of resveratrol and regular exercise training on cellular stress response were investigated in the hearts and kidneys of rats.Methods: Male and female Wistar rats (3-month-old) were used. Resveratrol (7.5 mg/kg, in the drinking water) and exercise training (for 40 minutes, three days per week) were applied for 6 weeks. The markers related to cellular stress were measured in left ventricle and kidney tissues.Results: Cardiac total antioxidant capacity (TAC) levels were greater in males than females, but no difference was observed in kidney tissue. Exercise training increased both TAC and nitrite levels in the heart in females but not in males. Even cardiac nitrite levels were decreased in males by exercise. Cardiac phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK) expression and renal glucose-regulated protein-78 (GRP78) expression were higher in the control male group compared to the female group. Cardiac tumor necrosis factor-ɑ (TNF-ɑ) expression was higher in females than males but not in kidneys. However, matrix metalloproteinase-2 (MMP-2) expression was higher in males than females in both kidney and cardiac tissues. The phospho-inhibitor κB-ɑ (p-IκB-ɑ) did not change between gender in cardiac tissues but had a decreased level in male kidneys compared to the female control group. Expression of phospho-extracellular signal-regulated kinase (p-ERK) in females and phospho-protein kinase B (p-Akt) in males were lower in kidney tissue. Resveratrol and exercise treatments markedly decreased Akt protein expression in male kidney tissue.Conclusion: Our findings indicate that the markers involved in cellular stress response were affected differently by the resveratrol and exercise treatments considering sex and tissue dependencies.

Anahtar Kelimeler

Cellular stress, Sex, Resveratrol, Exercise, Heart, Kidney

Destekleyen Kurum

Ankara University Research Foundation

Proje Numarası

12B3330001

Teşekkür

The authors are thankful to Prof. Dr. H. Gurdal and B. Dalkilic for supporting this research with the Western Blot experiments.

Kaynakça

• Bairey Merz, C.N., Dember, L.M., Ingelfinger, J.R., Vinson, A., … Star, R.A. (2019). Sex and the kidneys: Current understanding and research opportunities. Nature Reviews Nephrology, 15(12), 776 – 783. http://dx.doi.org/10.1038/s41581-019-0208-6.
• Bal, N.B., Han, S., Kiremitci, S., Uludag, M.O., & Demirel-Yilmaz, E. (2020). Reversal of deleterious effect of hypertension on the liver by inhibition of endoplasmic reticulum stress. Molecular Biology Reports, 47(3), 2243–2252. http://dx.doi.org/10.1007/s11033-020-05329-2.
• Balcı, S.S. & Pepe, H. (2012). Effects of gender, endurance training and acute exhaustive exercise on oxidative stress in the heart and skeletal muscle of the rat. Chinese Journal of Physiology, 55(4), 236–244. http://dx.doi.org/10.4077/CJP.2012.BAA021.
• Baylis, C. (2012). Nitric oxide synthase derangements and hypertension in kidney disease. Current Opinion in Nephrol- ogy and Hypertension, 21(1), 1–6. http://dx.doi.org/ 10.1097/ MNH.0b013e32834d54ca.
• Campesi, I., Franconi, F., Seghieri, G. & Meloni, M. (2017). Sex-gen- der-related therapeutic approaches for cardiovascular complica- tions associated with diabetes. Pharmacological Research, 119, 195–207http://dx.doi.org/10.1016/j.phrs.2017.01.023.
• Chemaly, E.R., Troncone, L. & Lebeche, D. (2018). SERCA control of cell death and survival. Cell Calcium, 69, 46–61. http://dx.doi. org/10.1016/j.ceca.2017.07.001.
• Chen, Y., Zhang, Y., Shan, M., Zhou, Y., Huang, Y. & Shi, L. (2019). Aerobic exercise-induced inhibition of PKCα/CaV1.2 pathway en- hances the vasodilation of mesenteric arteries in hypertension. Archives of Biochemistry and Biophysics,678, 108191. http://dx.doi. org/10.1016/j.abb.2019.108191.
• Cheng, C.K., Luo, J.Y., Lau, C.W., Chen, Z.Y., Tian, X.Y. & Huang, Y. (2020). Pharmacological basis and new insights of resveratrol ac- tion in the cardiovascular system. British Journal of Pharmacology, 177(6), 1258–1277. http://dx.doi.org/10.1111/bph.14801.
• Chengji, W. & Xianjin, F. (2019). Exercise protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway in rats. Journal of Cellular Physiology, 234(2), 1682– 1688. http://dx.doi.org/10.1002/jcp.27038.
• Dworatzek, E., Mahmoodzadeh, S., Schubert, C., Westphal, C., … Regitz-Zagrosek V. (2014). Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oes- trogen receptor beta. Cardiovascular Research, 102(3), 418–428. http://dx.doi.org/10.1093/cvr/cvu065.
• Erdely, A., Greenfeld, Z., Wagner, L. & Baylis, C. (2003). Sexual di- morphism in the aging kidney: Effects on injury and nitric ox- ide system. Kidney International, 63(3), 1021–1026. http://dx.doi. org/10.1046/j.1523-1755.2003.00830.x
• EUGenMed cardiovascular clinical study group, Regitz-Zagrosek, V., Oertelt-Prigione, S., Prescott, E., … Stangl, V. (2016). Gender in cardiovascular diseases: impact on clinical manifestations, man- agement, and outcomes. European Heart Journal, 37(1), 24–34. http://dx.doi.org/10.1093/eurheartj/ehv598.
• Farah, D., Nunes, J., Sartori, M., Dias, DD., … Angelis, K. (2016). exer- cise training prevents cardiovascular derangements induced by fructose overload in developing rats. PLoS One, 8;11(12):e0167291. http://dx.doi.org/10.1371/journal.pone.0167291.
• Fiordelisi, A., Iaccarino, G., Morisco, C., Coscioni, E. & Sorriento, D. (2019). NFkappaB is a key player in the crosstalk between inflam- mation and cardiovascular diseases. International Journal of Molec- ular Sciences, 20(7):1599. http://dx.doi.org/10.3390/ijms20071599.
• Gliemann, L., Nyberg, M. & Hellsten, Y. (2016). Effects of exercise training and Resveratrol on vascular health in aging. Free Radical Biology and Medicine, 98, 165–176. http://dx.doi.org/10.1016/j.fre- eradbiomed.2016.03.037.
• Han, S., Bal, N.B., Sadi, G., Usanmaz, S.E., Uludag, M.O. & Demirel- Yilmaz, E. (2018). The effects of resveratrol and exercise on age and gender-dependent alterations of vascular functions and bio- markers. Experimental Gerontology, 110, 191–201. http://dx.doi. org/10.1016/j.exger.2018.06.009.
• Hong, J., Kim, K., Kim, J.H. & Park, Y. (2017). The Role of Endoplas-mic Reticulum Stress in Cardiovascular Disease and Exercise.image29
• International Journal of Vascular Medicine 2017, 2049217. http:// dx.doi.org/10.1155/2017/2049217.
• Juhasz, B., Mukherjee, S., & Das DK. (2010). Hormetic response of resveratrol against cardioprotection. Experimental & Clinical Cardi- ology, 15(4):e134-e138.
• Katalinic, V., Modun, D., Music, I. & Boban, M. (2005). Gender dif- ferences in antioxidant capacity of rat tissues determined by 2,2’-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comparative Biochem- istry and Physiology - Part C: Toxicology & Pharmacology, 140(1), 47–52. http://dx.doi.org/10.1016/j.cca.2005.01.005.
• Kosaki, K., Sugaya, T., Ohata, K., Tanabe, J.,… Ikemori, A. (2019). Renoprotective effects of voluntary running exercise training on aldosterone-induced renal injury in human L-FABP chromo- somal transgenic mice. Hypertension Research, 42(10), 1518–1527. http://dx.doi.org/10.1038/s41440-019-0273-z.
• Li, H., Xia, N., & Förstermann, U. (2012). Cardiovascular effects and molecular targets of resveratrol. Nitric Oxide, 26(2), 102–110. https://doi.org/10.1016/j.niox.2011.12.006.
• Lin Y, Zhu J, Zhang X, Wang J, … Liu, J. (2016). inhibition of cardio- myocytes hypertrophy by resveratrol is associated with ameliora- tion of endoplasmic reticulum stress. Cellular Physiology and Bio- chemistry, 39(2), 780–789. http://dx.doi.org/10.1159/000447788.
• Liu, M., Ning, X., Li, R., Yang, Z., … Qian, Q. (2017). Signalling pathways involved in hypoxia-induced renal fibrosis. Journal of Cellular and Molecular Medicine, 21(7), 1248–1259. http://dx.doi. org/10.1111/jcmm.13060.
• Nasiri, M., Ahmadizad, S., Hedayati, M., Zarekar, T., Seydyousefi, M., & Faghfoori Z. (2021). Trans-resveratrol supplement lowers lipid peroxidation responses of exercise in male Wistar rats. Interna- tional Journal for Vitamin and Nutrition Research, 91(5-6):507-512. http://dx.doi.org/ 10.1024/0300-9831/a000654.
• Olesen, J., Ringholm, S., Nielsen, M.M., Brandt, C.T., … Pilegaard,H. (2013). Role of PGC-1α in exercise training- and resveratrol- induced prevention of age-associated inflammation. Experimen- tal Gerontology, 48(11), 1274–1284. http://dx.doi.org/10.1016/j. exger.2013.07.015.
• Pektaş, M.B., Sadi, G. & Akar, F. (2015). Long-Term Dietary Fruc- tose Causes Gender-Different Metabolic and Vascular Dys- function in Rats: Modulatory Effects of Resveratrol. Cellular Physiology and Biochemistry, 37(4), 1407–1420. http://dx.doi. org/10.1159/000430405.
• Rolim, N.P., Medeiros, A., Rosa, K.T., Mattos, K.C., … Brum, P.C. (2007). Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure. Physiological Genomics, 29(3), 246–252. http://dx.doi.org/10.1152/physiolge- nomics.00188.2006.
• Saghebjoo, M., Sadeghi-Tabas, S., Saffari, I., Ghane, A2. & Dimau- ro, I. (2019). Sex Differences in antiaging response to short- and long-term high-intensity interval exercise in rat cardiac muscle: Telomerase activity, total antioxidant/oxidant status. Chinese Journal of Physiology, 62(6), 261–266. http://dx.doi.org/10.4103/ CJP.CJP_52_19.
• Singh, A.P., Singh, R., Verma, S.S., Rai, V., … Gupta, S.C. (2019). Health benefits of resveratrol: Evidence from clinical studies. Medicinal Research Reviews, 39(5), 1851–1891. http://dx.doi. org/10.1002/med.21565.
• Soylemez, S., Gurdal, H., Sepici, A. & Akar, F. (2008). The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: role of nitric oxide and su- peroxide. Vascular Pharmacology, 49(2-3), 97–105. http://dx.doi. org/10.1016/j.vph.2008.06.006
• Soylemez, S., Sepici, A. & Akar, F. (2009). Resveratrol supplementa- tion gender independently improves endothelial reactivity and suppresses superoxide production in healthy rats. Cardiovascu- lar Drugs and Therapy, 23(6), 449–458. http://dx.doi.org/10.1007/ s10557-009-6198-z.
• Towbin, H., Staehelin, T. & Gordon, J. (1979). Electrophoretic trans- fer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences of the United States of America, 76(9), 4350– 4354. http://dx.doi.org/10.1073/pnas.76.9.4350.
• Tung, B.T., Rodriguez-Bies, E., Thanh, H.N., Le-Thi-Thu, H., … López-Lluch, G. (2015). Organ and tissue-dependent effect of res- veratrol and exercise on antioxidant defenses of old mice. Aging Clinical and Experimental Research, 27(6), 775–783. http://dx.doi. org/10.1007/s40520-015-0366-8.
• Usanmaz, S.E. & Demirel-Yilmaz, E. (2008). A microplate based spectrophotometric method for the determination of the total antioxidant capacity of human plasma: Modified cupric reduc- ing ability assay. Fundamental & Clinical Pharmacology, 22(Suppl. 2), 67.
• Zhang, J., Wang, X., Vikash, V., Ye, Q., … Dong, W. (2016). ROS and ROS-Mediated cellular signaling. Oxidative Medi- cine and Cellular Longevity, 2016, 4350965. http://dx.doi. org/10.1155/2016/4350965.
• Zhang, L., Zhang, Y., Wu, Y., Yu, J., … Shi, L. (2019). Role of the Balance of Akt and MAPK pathways in the exercise-regulated phenotype switching in spontaneously hypertensive rats. Inter- national Journal of Molecular Sciences, 20(22), 5690–5709. http:// dx.doi.org/10.3390/ijms20225690.