Nephro-protective effect of Daphnetin in hyperoxaluria-induced rat renal injury via alterations of the gut microbiota
Ruijun Zhou
Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorWenbin Wen
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorXiaoli Gong
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorYanxia Zhao
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorCorresponding Author
Wei Zhang
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Correspondence
Wei Zhang, Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046011, China.
Email: [email protected]
Search for more papers by this authorRuijun Zhou
Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorWenbin Wen
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorXiaoli Gong
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorYanxia Zhao
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Search for more papers by this authorCorresponding Author
Wei Zhang
Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
Correspondence
Wei Zhang, Department of Nephropathy, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi 046011, China.
Email: [email protected]
Search for more papers by this authorAbstract
It is well proved that hyperoxaluria induces the renal injury and finally causes the end stage kidney disease. Daphnetin (coumarin derivative) already confirmed renal protective effect in renal model, but hyperoxaluria protective effect still unexplore. The objective of this research was to scrutinize the renal protective effect of daphnetin against ethylene glycol (GC)-induced hyperoxaluria via altering the gut microbiota. GC (1% v/v) was used for the induction of hyperoxaluria in the rats and the rats were received the oral administration of daphnetin (5, 10 and 15 mg/kg). The body and renal weight were assessed. Urine, renal, inflammatory cytokines, antioxidant, inflammatory parameters, and gut microbiota were appraised. Daphnetin effectually improved the body weight and reduced the renal weight. Its also remarkably boosted the magnesium, calcium, citrate level and suppressed the level of uric acid and oxalate formation. Daphnetin significantly (p < .001) ameliorate the level of urinary kidney injury molecule 1 (KIM-1), blood urea nitrogen (BUN), urea, serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and uric acid along with inflammatory cytokines and inflammatory mediators. Daphnetin considerably repressed the malonaldehyde (MDA) level, protein carbonyl and improved the level of glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). Daphnetin treatment considerably altered the microbial composition of different bacteria at phylum, genus and family level. Daphnetin significantly suppressed the Firmicutes relative abundance and boosted the Bacteroidetes relative abundance. Our result clearly indicated that daphnetin remarkably ameliorates the GC induced hyperoxaluria in rats via altering the oxidative stress, inflammatory reaction and gut microbiota.
Practical application
Nephrotoxicity is a serious health disease worldwide. We induce the renal toxicity in the experimental rats using the ethylene glycol and scrutinized the renal protective effect of daphnetin. Daphnetin considerably suppress the renal, urine parameters. For estimation the underlying mechanism, we estimated the gut microbiota in all group rats. Daphnetin remarkably altered the level of gut microbiota and suggesting the renal protective effect.
CONFLICT OF INTEREST
The authors declared that they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- Adel, H., Sattar, A., Rahim, A., Aftab, A., & Adil, S. O. (2019). Diagnostic accuracy of doppler twinkling artifact for identifying urinary tract calculi. Cureus, 11, e5647. https://doi.org/10.7759/cureus.5647
- Aggarwal, D., Kaushal, R., Kaur, T., Bijarnia, R. K., Puri, S., & Singla, S. K. (2014). The most potent antilithiatic agent ameliorating renal dysfunction and oxidative stress from Bergenia ligulata rhizome. Journal of Ethnopharmacology, 158, 85–93. https://doi.org/10.1016/j.jep.2014.10.013
- Aggarwal, K. P., Narula, S., Kakkar, M., & Tandon, C. (2013). Nephrolithiasis: Molecular mechanism of renal stone formation and the critical role played by modulators. BioMed Research International, 2013, 292953. https://doi.org/10.1155/2013/292953
- Ahmed, O. M., Ebaid, H., El-Nahass, E. S., Ragab, M., & Alhazza, I. M. (2020). Nephroprotective effect of pleurotus ostreatus and agaricus bisporus extracts and carvedilol on ethylene glycol-induced urolithiasis: Roles of Nf-κb, P53, Bcl-2, Bax and Bak. Biomolecules, 10, 1–37. https://doi.org/10.3390/biom10091317
- Arik, H. O., Yalcin, A. D., Gumuslu, S., Genç, G. E., Turan, A., & Sanlioglu, A. D. (2013). Association of circulating sTRAIL and high-sensitivity CRP with type 2 diabetic nephropathy and foot ulcers. Medical Science Monitor, 19, 712–715. https://doi.org/10.12659/MSM.889514
- Azimi, A., Eidi, A., Mortazavi, P., & Rohani, A. H. (2021). Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats. Life Sciences, 279, 119641. https://doi.org/10.1016/j.lfs.2021.119641
- Cao, L. C., Jonassen, J., Honeyman, T. W., & Scheid, C. (2001). Oxalate-induced redistribution of phosphatidylserine in renal epithelial cells: Implications for kidney stone disease. American Journal of Nephrology, 21, 69–77. https://doi.org/10.1159/000046224
- Cawthorn, W. P., & Sethi, J. K. (1998). TNF-a and adipocyte biology. Diabetes Research and Clinical Practice, 17, 117–131.
- Chaiyarit, S., & Thongboonkerd, V. (2020). Mitochondrial dysfunction and kidney stone disease. Frontiers in Physiology, 11, 566506. https://doi.org/10.3389/fphys.2020.566506
- Chen, Y. L., Qiao, Y. C., Xu, Y., Ling, W., Pan, Y. H., Huang, Y. C., Geng, L. J., Zhao, H. L., & Zhang, X. X. (2017). Serum TNF-α concentrations in type 2 diabetes mellitus patients and diabetic nephropathy patients: A systematic review and meta-analysis. Immunology Letters, 186, 52–58. https://doi.org/10.1016/j.imlet.2017.04.003
- Cianci, P., & Restini, E. (2021). Management of cholelithiasis with choledocholithiasis: Endoscopic and surgical approaches. World Journal of Gastroenterology, 27, 4536–4554. https://doi.org/10.3748/wjg.v27.i28.4536
- Convento, M. B., Pessoa, E. A., Cruz, E., Da Glória, M. A., Schor, N., & Borges, F. T. (2017). Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: Contribution to oxalate kidney injury. Scientific Reports, 7, 45740. https://doi.org/10.1038/srep45740
- De Sordi, L., Khanna, V., & Debarbieux, L. (2017). The gut microbiota facilitates drifts in the genetic diversity and infectivity of bacterial viruses. Cell Host & Microbe, 22, 801–808.e3. https://doi.org/10.1016/j.chom.2017.10.010
- Grases, F., Genestar, C., Conte, A., March, P., & Costa-Bauza, A. (1989). Inhibitory effect of pyrophosphate, citrate, magnesium and chondroitin sulphate in calcium oxalate urolithiasis. British Journal of Urology, 64, 235–237. https://doi.org/10.1111/j.1464-410X.1989.tb06004.x
- Green, M. L., Hatch, M., & Freel, R. W. (2005). Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats. American Journal of Physiology-Renal Physiology, 289, F536–F543. https://doi.org/10.1152/ajprenal.00025.2005
- Hackett, R. L., Shevock, P. N., & Khan, S. R. (1990). Cell injury associated calcium oxalate crystalluria. The Journal of Urology, 144, 1535–1538. https://doi.org/10.1016/S0022-5347(17)39793-8
- Jiang, S., Tang, Y., Bao, Y., Su, X., Li, K., Guo, Y., Liu, Z., & Song, W. (2019). Protective effect of Coptis chinensis polysaccharide against renal injury by suppressing oxidative stress and inflammation in diabetic rats. Natural Product Communications, 14(9), 1–7. https://doi.org/10.1177/1934578X19860998
- Jiang, S., Xie, S., Lv, D., Wang, P., He, H., Zhang, T., Zhou, Y., Lin, Q., Zhou, H., Jiang, J., Nie, J., Hou, F., & Chen, Y. (2017). Alteration of the gut microbiota in Chinese population with chronic kidney disease. Scientific Reports, 7, 1–10. https://doi.org/10.1038/s41598-017-02989-2
- Khan, A., Bashir, S., Khan, S. R., & Gilani, A. H. (2011). Antiurolithic activity of Origanum vulgare is mediated through multiple pathways. BMC Complementary and Alternative Medicine, 11, 96. https://doi.org/10.1186/1472-6882-11-96
- Khan, S. R. (2005). Hyperoxaluria-induced oxidative stress and antioxidants for renal protection. Urological Research, 33, 349–357. https://doi.org/10.1007/s00240-005-0492-4
- Khan, S. R. (2014). Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. Translational Andrology and Urology, 3, 256. https://doi.org/10.3978/j.issn.2223-4683.2014.06.04
- Khand, F. D., Gordge, M. P., Robertson, W. G., Noronha-Dutra, A. A., & Hothersall, J. S. (2002). Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells. Free Radical Biology & Medicine, 32, 1339–1350. https://doi.org/10.1016/S0891-5849(02)00846-8
- Kohri, K. (1994). Pathogenesis of urolithiasis. Nihon Hinyokika Gakkai zasshi. The Japanese Journal of Urology, 85, 552–562. https://doi.org/10.5980/jpnjurol1989.85.552
- Leemans, J. C., Butter, L. M., Pulskens, W. P. C., Teske, G. J. D., Claessen, N., van der Poll, T., & Florquin, S. (2009). The role of toll-like receptor 2 in inflammation and fibrosis during progressive renal injury. PLoS One, 4, e5704. https://doi.org/10.1371/journal.pone.0005704
- Leveridge, M., D'Arcy, F. T., O'Kane, D., Ischia, J. J., Webb, D. R., Bolton, D. M., & Lawrentschuk, N. (2016). Renal colic: Current protocols for emergency presentations. European Journal of Emergency Medicine, 23, 2–7. https://doi.org/10.1097/MEJ.0000000000000324
- Liu, C., Zhao, S., Zhu, C., Gao, Q., Bai, J., Si, J., & Chen, Y. (2020). Ergosterol ameliorates renal inflammatory responses in mice model of diabetic nephropathy. Biomedicine & Pharmacotherapy, 128, 110252. https://doi.org/10.1016/j.biopha.2020.110252
- Liu, X., Gao, X., Liu, Y., Liang, D., Fu, T., Song, Y., Zhao, C., Dong, B., & Han, W. (2019). Daphnetin inhibits RANKL-induced osteoclastogenesis in vitro. Journal of Cellular Biochemistry, 120, 2304–2312. https://doi.org/10.1002/jcb.27555
- Liu, Y., Chen, Y., Liao, B., Luo, D., Wang, K., Li, H., & Zeng, G. (2018). Epidemiology of urolithiasis in Asia. Asian Journal of Urology, 5(4), 205–214. https://doi.org/10.1016/j.ajur.2018.08.007
- Miller, C., Kennington, L., Cooney, R., Kohjimoto, Y., Cao, L. C., Honeyman, T., Pullman, J., Jonassen, J., & Scheid, C. (2000). Oxalate toxicity in renal epithelial cells: Characteristics of apoptosis and necrosis. Toxicology and Applied Pharmacology, 162, 132–141. https://doi.org/10.1006/taap.1999.8835
- Mistry, K. N., Dabhi, B. K., & Joshi, B. B. (2020). Evaluation of oxidative stress biomarkers and inflammation in pathogenesis of diabetes and diabetic nephropathy. Indian Journal of Biochemistry & Biophysics, 57, 45–50.
- Nagase, N., Ikeda, Y., Tsuji, A., Kitagishi, Y., & Matsuda, S. (2022). Efficacy of probiotics on the modulation of gut microbiota in the treatment of diabetic nephropathy. World Journal of Diabetes, 13, 150–160. https://doi.org/10.4239/wjd.v13.i3.150
- Naghii, M. R., Jafari, M., Mofid, M., Eskandari, E., Hedayati, M., & Khalagie, K. (2015). The efficacy of antioxidant therapy against oxidative stress and androgen rise in ethylene glycol induced nephrolithiasis in Wistar rats. Human & Experimental Toxicology, 34, 744–754. https://doi.org/10.1177/0960327114558889
- Ozturk, H., Cetinkaya, A., Firat, T. S., Tekce, B. K., Duzcu, S. E., & Ozturk, H. (2019). Protective effect of pentoxifylline on oxidative renal cell injury associated with renal crystal formation in a hyperoxaluric rat model. Urolithiasis, 47, 415–424. https://doi.org/10.1007/s00240-018-1072-8
- Saeidi, J., Bozorgi, H., Zendehdel, A., & Mehrzad, J. (2012). Therapeutic effects of aqueous extracts of Petroselinum Sativum on ethylene glycol-induced kidney calculi in rats. Urology Journal, 9, 361–366.
- Scales, C. D. (2013). Epidemiology of stone disease. In Clinical management of urolithiasis (pp. 1–8). Springer. https://doi.org/10.1007/978-3-642-28732-9_1
10.1007/978-3-642-28732-9_1 Google Scholar
- Shen, M., Liu, C., Wan, X., Farah, N., & Fang, L. (2018). Development of a daphnetin transdermal patch using chemical enhancer strategy: Insights of the enhancement effect of Transcutol P and the assessment of pharmacodynamics. Drug Development and Industrial Pharmacy, 44, 1642–1649. https://doi.org/10.1080/03639045.2018.1483391
- Singh, L., Kaur, A., Singh, A. P., & Bhatti, R. (2021). Daphnetin, a natural coumarin averts reserpine-induced fibromyalgia in mice: Modulation of MAO-A. Experimental Brain Research, 239, 1451–1463. https://doi.org/10.1007/s00221-021-06064-1
- Sorokin, I., Mamoulakis, C., Miyazawa, K., Rodgers, A., Talati, J., & Lotan, Y. (2017). Epidemiology of stone disease across the world. World Journal of Urology, 35, 1301–1320. https://doi.org/10.1007/s00345-017-2008-6
- Thamilselvan, S., Khan, S. R., & Menon, M. (2003). Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: Effect of antioxidants. Urological Research, 31, 3–9. https://doi.org/10.1007/s00240-002-0286-x
- Thamilselvan, S., & Menon, M. (2005). Vitamin E therapy prevents hyperoxaluria-induced calcium oxalate crystal deposition in the kidney by improving renal tissue antioxidant status. BJU International, 96, 117–126. https://doi.org/10.1111/j.1464-410X.2005.05579.x
- Tsuji, H., Wang, W., Sunil, J., Shimizu, N., Yoshimura, K., Uemura, H., Peck, A. B., & Khan, S. R. (2016). Involvement of renin–angiotensin–aldosterone system in calcium oxalate crystal induced activation of NADPH oxidase and renal cell injury. World Journal of Urology, 34, 89–95. https://doi.org/10.1007/s00345-015-1563-y
- Wang, G., Pang, J., Hu, X., Nie, T., Lu, X., Li, X., Wang, X., Lu, Y., Yang, X., Jiang, J., Li, C., Xiong, Y. Q., & You, X. (2019). Daphnetin: A novel anti-helicobacter pylori agent. International Journal of Molecular Sciences, 20(4), 850. https://doi.org/10.3390/ijms20040850
- Wang, W., Fan, J., Huang, G., Li, J., Zhu, X., Tian, Y., & Su, L. (2017). Prevalence of kidney stones in mainland China: A systematic review. Scientific Reports, 7, 41630. https://doi.org/10.1038/srep41630
- Wu, Y., Xun, Y., Zhang, J., Hu, H., Qin, B., Wang, T., Wang, S., Li, C., & Lu, Y. (2021). Resveratrol attenuates oxalate-induced renal oxidative injury and calcium oxalate crystal deposition by regulating TFEB-induced autophagy pathway. Frontiers in Cell and Development Biology, 9, 638759. https://doi.org/10.3389/fcell.2021.638759
- Xu, K., Guo, L., Bu, H., & Wang, H. (2019). Daphnetin inhibits high glucose-induced extracellular matrix accumulation, oxidative stress and inflammation in human glomerular mesangial cells. Journal of Pharmacological Sciences, 139, 91–97. https://doi.org/10.1016/j.jphs.2018.11.013
- Yang, S., Song, Y., Wang, Q., Liu, Y., Wu, Z., Duan, X., Zhang, Y., Bi, X., Geng, Y., Chen, S., & Zhu, C. (2021). Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway. Scientific Reports, 11, 11491. https://doi.org/10.1038/s41598-021-91008-6
- Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018). The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nature Reviews. Nephrology, 14, 442–456. https://doi.org/10.1038/s41581-018-0018-2
- Yu, W. W., Lu, Z., Zhang, H., Kang, Y. H., Mao, Y., Wang, H. H., Ge, W. H., & Shi, L. Y. (2014). Anti-inflammatory and protective properties of Daphnetin in endotoxin-induced lung injury. Journal of Agricultural and Food Chemistry, 62, 12315–12325. https://doi.org/10.1021/jf503667v
- Zhang, X., Yao, J., Wu, Z., Zou, K., Yang, Z., Huang, X., Luan, Z., Li, J., & Wei, Q. (2020). Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models. Life Sciences, 240, 116857. https://doi.org/10.1016/j.lfs.2019.116857
- Zhang, Y. Y., Tan, R. Z., Zhang, X. Q., Yu, Y., & Yu, C. (2019). Calycosin ameliorates diabetes-induced renal inflammation via the nf-kb pathway in vitro and in vivo. Medical Science Monitor, 25, 1671–1678. https://doi.org/10.12659/MSM.915242
- Zhu, W., Liu, Y., Duan, X., Xiao, C., Lan, Y., Luo, L., Wu, C., Yang, Z., Mai, X., Lu, S., Zhong, W., Li, S., He, Z., Zhang, X., Liu, Y., & Zeng, G. (2020). Alteration of the gut microbiota by vinegar is associated with amelioration of hyperoxaluria-induced kidney injury. Food & Function, 11, 2639–2653. https://doi.org/10.1039/c9fo02172h