Resveratrol: A new approach to ameliorate hyperhomocysteinaemia-induced renal dysfunction

Zhao,Xuan; Hui,Qing-Chen; Xu,Rui; Gao,Ning; Cao,Ping

doi:10.3892/etm.2022.11437

Resveratrol: A new approach to ameliorate hyperhomocysteinaemia-induced renal dysfunction

Authors:
- Xuan Zhao
- Qing-Chen Hui
- Rui Xu
- Ning Gao
- Ping Cao
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Affiliations: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Cardiology, Jimo District Qingdao Hospital of Traditional Chinese Medicine, Qingdao, Shandong 266200, P.R. China, Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China, Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China, Department of Geriatric Medicine, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China
Published online on: June 10, 2022 https://doi.org/10.3892/etm.2022.11437
Article Number: 510

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Abstract

Hypertension is a common cause of kidney injury and renal damage occurs earlier and is more serious in patients with hypertension and hyperhomocysteinaemia (HHCY). Folic acid (FA) is widely used to ameliorate the organ damage caused by HHCY. However, the effective dose of FA remains controversial and certain studies have suggested that FA increases the risk of cancer. Therefore, it is necessary to identify a safe, effective drug. Resveratrol (RSV) is a natural polyphenol antioxidant. Therefore, the present study explored the effects of RSV on renal damage in spontaneously hypertensive rats (SHRs) with HHCY and its potential underlying mechanism. SHRs were divided randomly into control, HHCY, HHCY + FA and HHCY + RSV groups. Blood pressure, plasma homocysteine, indexes of oxidative stress [serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels] and indexes of renal function [glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR)] were assessed. The mRNA and protein expression levels of nephrin and NAPDH oxidase (NOX)2 and NOX4 were detected via reverse transcription‑quantitative PCR and western blotting. The results demonstrated that there was no significant difference in BP (blood pressure) among the groups, while the levels of homocysteine (HCY) in the HHCY intervention groups were significantly increased compared with the control. Both FA and RSV decreased the level of HCY, but the decrease was more obvious in the HHCY + FA group. Compared with the control the serum SOD levels and GFR were significantly decreased in the HHCY group, whereas the serum MDA levels and UACR were significantly increased. Moreover, the NOX2 and NOX4 expression levels were significantly increased, whereas those of nephrin were significantly decreased in the HHCY group. The changes caused by HHCY were significantly counteracted in both the HHCY + FA and HHCY + RSV groups and the antioxidant effect was markedly stronger in the HHCY + RSV group. In conclusion, RSV, like FA, potentially improved the renal function damage aggravated by HHCY in SHRs. Furthermore, RSV improved renal function mainly via the inhibition of oxidative stress. RSV may be a potential safe and effective treatment for HHCY‑induced hypertensive renal damage.

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1	Finkelstein JD and Martin JJ: Homocysteine. Int J Biochem Cell Biol. 32:385–389. 2000.PubMed/NCBI View Article : Google Scholar
2	Zaric BL, Obradovic M, Bajic V, Haidara MA, Jovanovic M and Isenovic ER: Homocysteine and Hyperhomocysteinaemia. Curr Med Chem. 26:2948–2961. 2019.PubMed/NCBI View Article : Google Scholar
3	Zhou YF and Guan YF: Hyperhomocysteinemia and kidney diseases. Sheng Li Xue Bao. 70:607–611. 2018.PubMed/NCBI(In Chinese).
4	Zhao W, Gao F, Lv L and Chen X: The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States. J Hypertens. 40:254–263. 2022.PubMed/NCBI View Article : Google Scholar
5	Ye Z, Wang C, Zhang Q, Li Y, Zhang J, Ma X, Peng H and Lou T: Prevalence of homocysteine-related hypertension in patients with chronic kidney disease. J Clin Hypertens (Greenwich). 19:151–160. 2017.PubMed/NCBI View Article : Google Scholar
6	Xie D, Yuan Y, Guo J, Yang S, Xu X, Wang Q, Li Y, Qin X, Tang G, Huo Y, et al: Hyperhomocysteinemia predicts renal function decline: A prospective study in hypertensive adults. Sci Rep. 5(16268)2015.PubMed/NCBI View Article : Google Scholar
7	Long Y and Nie J: Homocysteine in renal injury. Kidney Dis (Basel). 2:80–87. 2016.PubMed/NCBI View Article : Google Scholar
8	Guo G, Sun W, Liu G, Zheng H and Zhao J: Comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia. Clin Exp Hypertens. 40:262–266. 2018.PubMed/NCBI View Article : Google Scholar
9	Gao N, Zhang Y, Li L, Lei L, Cao P, Zhao X, Lin L and Xu R: Hyperhomocysteinemia-induced oxidative stress aggravates renal damage in hypertensive rats. Am J Hypertens. 33:1127–1135. 2020.PubMed/NCBI View Article : Google Scholar
10	Gao N, Zhang Y, Lei L, Li L, Cao P, Zhao X, Lin L and Xu R: Low doses of folic acid can reduce hyperhomocysteinemia-induced glomerular injury in spontaneously hypertensive rats. Hypertens Res. 43:1182–1191. 2020.PubMed/NCBI View Article : Google Scholar
11	Shulpekova Y, Nechaev V, Kardasheva S, Sedova A, Kurbatova A, Bueverova E, Kopylov A, Malsagova K, Dlamini JC and Ivashkin V: The concept of folic acid in health and disease. Molecules. 26(3731)2021.PubMed/NCBI View Article : Google Scholar
12	Den*Hartogh DJ and Tsiani E: Health benefits of resveratrol in kidney disease: Evidence from in vitro and in vivo studies. Nutrients. 11(1624)2019.PubMed/NCBI View Article : Google Scholar
13	Cheng CK, Luo JY, Lau CW, Chen ZY, Tian XY and Huang Y: Pharmacological basis and new insights of resveratrol action in the cardiovascular system. Br J Pharmacol. 177:1258–1277. 2020.PubMed/NCBI View Article : Google Scholar
14	Breuss JM, Atanasov AG and Uhrin P: Resveratrol and its effects on the vascular system. Int J Mol Sci. 20(1523)2019.PubMed/NCBI View Article : Google Scholar
15	Pyo IS, Yun S, Yoon YE, Choi JW and Lee SJ: Mechanisms of aging and the preventive effects of resveratrol on age-related diseases. Molecules. 25(4649)2020.PubMed/NCBI View Article : Google Scholar
16	Atazadegan MA, Bagherniya M, Askari G, Tasbandi A and Sahebkar A: The effects of medicinal plants and bioactive natural compounds on homocysteine. Molecules. 26(3081)2021.PubMed/NCBI View Article : Google Scholar
17	Koz ST, Etem EO, Baydas G, Yuce H, Ozercan HI, Kuloğlu T, Koz S, Etem A and Demir N: Effects of resveratrol on blood homocysteine level, on homocysteine induced oxidative stress, apoptosis and cognitive dysfunctions in rats. Brain Res. 1484:29–38. 2012.PubMed/NCBI View Article : Google Scholar
18	Li D, Cui Z, Xu S, Xu T, Wu S, Bouakaz A, Wan M and Zhang S: Low-intensity focused ultrasound stimulation treatment decreases blood pressure in spontaneously hypertensive rats. IEEE Trans Biomed Eng. 67:3048–3056. 2020.PubMed/NCBI View Article : Google Scholar
19	Reastuty R and Haryuna TSH: Correlation of SOD and MDA expression in the organ of corti and changes in the function of outer hair cells measured by DPOAE examination in noise-exposed rat cochlea. Rep Biochem Mol Biol. 10:41–49. 2021.PubMed/NCBI View Article : Google Scholar
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
21	Liu C, Lin L and Xu R: Elevated homocysteine and differential risks of the renal function decline in hypertensive patients. Clin Exp Hypertens. 42:565–570. 2020.PubMed/NCBI View Article : Google Scholar
22	Pieroth R, Paver S, Day S and Lammersfeld C: Folate and its impact on cancer risk. Curr Nutr Rep. 7:70–84. 2018.PubMed/NCBI View Article : Google Scholar
23	Salami M, Salami R, Mafi A, Aarabi MH, Vakili O and Asemi Z: Therapeutic potential of resveratrol in diabetic nephropathy according to molecular signaling. Curr Mol Pharmacol: Dec 17, 2021 (Epub ahead of print).
24	Li KX, Ji MJ and Sun HJ: An updated pharmacological insight of resveratrol in the treatment of diabetic nephropathy. Gene. 780(145532)2021.PubMed/NCBI View Article : Google Scholar
25	Chudzińska M, Rogowicz D, Wołowiec Ł, Banach J, Sielski S, Bujak R, Sinkiewicz A and Grześk G: Resveratrol and cardiovascular system-the unfulfilled hopes. Ir J Med Sci. 190:981–986. 2021.PubMed/NCBI View Article : Google Scholar
26	Parsamanesh N, Asghari A, Sardari S, Tasbandi A, Jamialahmadi T, Xu S and Sahebkar A: Resveratrol and endothelial function: A literature review. Pharmacol Res. 170(105725)2021.PubMed/NCBI View Article : Google Scholar
27	Dolinsky VW, Chakrabarti S, Pereira TJ, Oka T, Levasseur J, Beker D, Zordoky BN, Morton JS, Nagendran J, Lopaschuk GD, et al: Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice. Biochim Biophys Acta. 1832:1723–1733. 2013.PubMed/NCBI View Article : Google Scholar
28	Park S, Lee S, Kim Y, Cho S, Kim K, Kim YC, Han SS, Lee H, Lee JP, Joo KW, et al: Causal effects of homocysteine, folate, and cobalamin on kidney function: A mendelian randomization study. Nutrients. 13(906)2021.PubMed/NCBI View Article : Google Scholar
29	Wartiovaara J, Ofverstedt LG, Khoshnoodi J, Zhang J, Mäkelä E, Sandin S, Ruotsalainen V, Cheng RH, Jalanko H, Skoglund U and Tryggvason K: Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. J Clin Invest. 114:1475–1483. 2004.PubMed/NCBI View Article : Google Scholar
30	Tryggvason K and Wartiovaara J: Molecular basis of glomerular permselectivity. Curr Opin Nephrol Hypertens. 10:543–549. 2001.PubMed/NCBI View Article : Google Scholar
31	Xia M, Conley SM, Li G, Li PL and Boini KM: Inhibition of hyperhomocysteinemia-induced inflammasome activation and glomerular sclerosis by NLRP3 gene deletion. Cell Physiol Biochem. 34:829–841. 2014.PubMed/NCBI View Article : Google Scholar
32	Li H, Xia N, Hasselwander S and Daiber A: Resveratrol and vascular function. Int J Mol Sci. 20(2155)2019.PubMed/NCBI View Article : Google Scholar
33	Luo M, Cao C, Niebauer J, Yan J, Ma X, Chang Q, Zhang T, Huang X and Liu G: Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats. J Cell Mol Med. 25:8522–8536. 2021.PubMed/NCBI View Article : Google Scholar
34	Buccitelli C and Selbach M: mRNAs, proteins and the emerging principles of gene expression control. Nat Rev Genet. 21:630–644. 2020.PubMed/NCBI View Article : Google Scholar