Resveratrol Butyrate Esters Reduce Hypertension in a Juvenile Rat Model of Chronic Kidney Disease Exacerbated by Microplastics

Overview

Journal Nutrients

Date 2024 Dec 17

PMID 39683469

Authors

Yi-Ning Huang

Chien-Ning Hsu

Chih-Yao Hou

Shin-Yu Chen

You-Lin Tain

Affiliations

Soon will be listed here.

Abstract

Background: Resveratrol is recognized as a promising nutraceutical with antihypertensive and prebiotic properties; however, its bioavailability in vivo is limited. To enhance its bioactivity, we developed resveratrol butyrate esters (RBEs). This study investigates whether RBEs can mitigate hypertension induced by chronic kidney disease (CKD) and exacerbated by microplastics (MPs) exposure in juvenile rats.

Methods: Three-week-old male Sprague Dawley rats were fed either regular chow or 0.5% adenine chow for three weeks. The adenine-fed CKD rats (N = 8 per group) received either 5 μM MPs (10 mg/L) or MPs combined with RBE (25 mg/L) in their drinking water from weeks 3 to 9.

Results: Our results indicate that MP exposure worsened CKD-induced hypertension, while RBE treatment resulted in a reduction in systolic BP by 15 mmHg (155 ± 2 mmHg vs. 140 ± 1 mmHg, < 0.05). The combined exposure to adenine and MPs was associated with nitric oxide (NO) deficiency, which RBE treatment alleviated. Additionally, our findings revealed that RBE modulated both the classical and nonclassical renin-angiotensin system (RAS), contributing to its protective effects. We also observed changes in gut microbiota composition, increased butyric acid levels, and elevated renal GPR41 expression associated with RBE treatment.

Conclusions: In conclusion, in this juvenile rat model of combined CKD and MP exposure, RBE demonstrates antihypertensive effects by modulating NO levels, the RAS, gut microbiota, and their metabolites.

Citing Articles

Beneficial Effects of Butyrate on Kidney Disease.

Diep T, Liu H, Yan L Nutrients. 2025; 17(5).

PMID: 40077642 PMC: 11901450. DOI: 10.3390/nu17050772.

References

Hsu C, Hou C, Chang C, Tain Y . Resveratrol Butyrate Ester Protects Adenine-Treated Rats against Hypertension and Kidney Disease by Regulating the Gut-Kidney Axis. Antioxidants (Basel). 2022; 11(1). PMC: 8772985. DOI: 10.3390/antiox11010083. View

Thorakkattu P, Khanashyam A, Shah K, Sajith Babu K, Mundanat A, Deliephan A . Postbiotics: Current Trends in Food and Pharmaceutical Industry. Foods. 2022; 11(19). PMC: 9564201. DOI: 10.3390/foods11193094. View

Petrovski G, Gurusamy N, Das D . Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci. 2011; 1215:22-33. DOI: 10.1111/j.1749-6632.2010.05843.x. View

Natalin H, Garcia A, Ramalho L, Restini C . Resveratrol improves vasoprotective effects of captopril on aortic remodeling and fibrosis triggered by renovascular hypertension. Cardiovasc Pathol. 2016; 25(2):116-9. DOI: 10.1016/j.carpath.2015.11.003. View

Bird J, Raederstorff D, Weber P, Steinert R . Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota. Adv Nutr. 2017; 8(6):839-849. PMC: 5682996. DOI: 10.3945/an.117.016568. View

Oliveira R, Pelepenko L, Masaro D, Lustosa G, de Oliveira M, Roza N . Effects of microplastics on the kidneys: a narrative review. Kidney Int. 2024; 106(3):400-407. DOI: 10.1016/j.kint.2024.05.023. View

Shih M, Tain Y, Chen Y, Hsu W, Yeh Y, Chang S . Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats. Molecules. 2021; 26(13). PMC: 8271435. DOI: 10.3390/molecules26134010. View

Walle T, Hsieh F, DeLegge M, Oatis Jr J, Walle U . High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004; 32(12):1377-82. DOI: 10.1124/dmd.104.000885. View

Bode-Boger S, Scalera F, Ignarro L . The L-arginine paradox: Importance of the L-arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007; 114(3):295-306. DOI: 10.1016/j.pharmthera.2007.03.002. View

10.

Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F . From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016; 165(6):1332-1345. DOI: 10.1016/j.cell.2016.05.041. View

11.

Zhang Z, Chen W, Chan H, Peng J, Zhu P, Li J . Polystyrene microplastics induce size-dependent multi-organ damage in mice: Insights into gut microbiota and fecal metabolites. J Hazard Mater. 2023; 461:132503. DOI: 10.1016/j.jhazmat.2023.132503. View

12.

Tain Y, Hsu C . Developmental Programming of the Metabolic Syndrome: Can We Reprogram with Resveratrol?. Int J Mol Sci. 2018; 19(9). PMC: 6164855. DOI: 10.3390/ijms19092584. View

13.

Kshirsagar A, Zeitler E, Weaver A, Franceschini N, Engel L . Environmental Exposures and Kidney Disease. Kidney360. 2023; 3(12):2174-2182. PMC: 9802544. DOI: 10.34067/KID.0007962021. View

14.

Baylis C . Nitric oxide synthase derangements and hypertension in kidney disease. Curr Opin Nephrol Hypertens. 2011; 21(1):1-6. PMC: 3277934. DOI: 10.1097/MNH.0b013e32834d54ca. View

15.

Reckelhoff J . Gender differences in the regulation of blood pressure. Hypertension. 2001; 37(5):1199-208. DOI: 10.1161/01.hyp.37.5.1199. View

16.

Bohn T . Dietary factors affecting polyphenol bioavailability. Nutr Rev. 2014; 72(7):429-52. DOI: 10.1111/nure.12114. View

17.

Zou H, Chen Y, Qu H, Sun J, Wang T, Ma Y . Microplastics Exacerbate Cadmium-Induced Kidney Injury by Enhancing Oxidative Stress, Autophagy, Apoptosis, and Fibrosis. Int J Mol Sci. 2022; 23(22). PMC: 9694236. DOI: 10.3390/ijms232214411. View

18.

Oh W, Shahidi F . Antioxidant activity of resveratrol ester derivatives in food and biological model systems. Food Chem. 2018; 261:267-273. DOI: 10.1016/j.foodchem.2018.03.085. View

19.

Sahebkar A, Serban C, Ursoniu S, Wong N, Muntner P, Graham I . Lack of efficacy of resveratrol on C-reactive protein and selected cardiovascular risk factors--Results from a systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2015; 189:47-55. DOI: 10.1016/j.ijcard.2015.04.008. View

20.

Robinson C, Chanchlani R . High Blood Pressure in Children and Adolescents: Current Perspectives and Strategies to Improve Future Kidney and Cardiovascular Health. Kidney Int Rep. 2022; 7(5):954-970. PMC: 9091586. DOI: 10.1016/j.ekir.2022.02.018. View