Effect of Geumgwe-Sinkihwan on Renal Dysfunction in Ischemia/Reperfusion-Induced Acute Renal Failure Mice

Overview

Journal Nutrients

Date 2021 Nov 27

PMID 34836115

Authors

Byung Hyuk Han

Hyeon Kyoung Lee

Se Hoon Jang

Ai Lin Tai

Youn Jae Jang

Jung Joo Yoon

Hye Yoom Kim

Ho Sub Lee

Yun Jung Lee

Dae Gill Kang

Affiliations

Soon will be listed here.

Abstract

Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure (ARF). Geumgwe-sinkihwan (GSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon" in 1884. GSH has been used for treatment for patients with diabetes and glomerulonephritis caused by deficiency of kidney yang and insufficiency of kidney gi. Here we investigate the effects of GSH in mice model of ischemic acute kidney injury. The mice groups are as follows; sham group: C57BL6 male mice, I/R group: C57BL6 male mice with I/R surgery, GSH low group: I/R + 100 mg/kg/day GSH, and GSH high group: I/R + 300 mg/kg/day GSH. Ischemia was induced by clamping both renal arteries and reperfusion. Mice were orally given GSH (100 and 300 mg/kg/day) during 3 days after surgery. Treatment with GSH significantly ameliorated creatinine clearance, creatinine, and blood urea nitrogen levels. Treatment with GSH reduced neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), specific renal injury markers. GSH also reduced the periodic acid-Schiff and picro sirius red staining intensity in kidney of I/R group. Western blot and real-time RT-qPCR analysis demonstrated that GSH decreased protein and mRNA expression levels of the inflammatory cytokines in I/R-induced ARF mice. Moreover, GSH inhibited protein and mRNA expression of inflammasome-related protein including NLRP3 (NOD-like receptor pyrin domain-containing protein 3, cryoprin), ASC (Apoptosis-associated speck-like protein containing a CARD), and caspase-1. These findings provided evidence that GSH ameliorates renal injury including metabolic dysfunction and inflammation via the inhibition of NLRP3-dependent inflammasome in I/R-induced ARF mice.

References

Mori K, Lee H, Rapoport D, Drexler I, Foster K, Yang J . Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest. 2005; 115(3):610-21. PMC: 548316. DOI: 10.1172/JCI23056. View

Fernandez-Llama P, Andrews P, Nielsen S, Ecelbarger C, Knepper M . Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome. Kidney Int. 1998; 53(5):1244-53. DOI: 10.1046/j.1523-1755.1998.00878.x. View

Bellomo R, Kellum J, Bagshaw S . Normotensive ischemic acute renal failure. N Engl J Med. 2007; 357(21):2205. View

Xiang H, Zhu F, Xu Z, Xiong J . Role of Inflammasomes in Kidney Diseases via Both Canonical and Non-canonical Pathways. Front Cell Dev Biol. 2020; 8:106. PMC: 7056742. DOI: 10.3389/fcell.2020.00106. View

Moses A, Miller M, Streeten D . Pathophysiologic and pharmacologic alterations in the release and action of ADH. Metabolism. 1976; 25(6):697-721. DOI: 10.1016/0026-0495(76)90067-6. View

Kim S, Jeon Y, Lee J, Kang D, Kook H, Ahn K . Diminished adenylate cyclase activity and aquaporin 2 expression in acute renal failure rats. Kidney Int. 2000; 57(4):1643-50. DOI: 10.1046/j.1523-1755.2000.00008.x. View

Kwon T, Frokiaer J, Fernandez-Llama P, Knepper M, Nielsen S . Reduced abundance of aquaporins in rats with bilateral ischemia-induced acute renal failure: prevention by alpha-MSH. Am J Physiol. 1999; 277(3):F413-27. DOI: 10.1152/ajprenal.1999.277.3.F413. View

Sutterwala F, Ogura Y, Flavell R . The inflammasome in pathogen recognition and inflammation. J Leukoc Biol. 2007; 82(2):259-64. DOI: 10.1189/jlb.1206755. View

Kidher E, Harling L, Ashrafian H, Naase H, Chukwuemeka A, Anderson J . Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors of acute kidney injury following aortic valve replacement. J Cardiothorac Surg. 2014; 9:89. PMC: 4057558. DOI: 10.1186/1749-8090-9-89. View

10.

Fioretto P, Mauer M . Histopathology of diabetic nephropathy. Semin Nephrol. 2007; 27(2):195-207. PMC: 2746982. DOI: 10.1016/j.semnephrol.2007.01.012. View

11.

Filho L, Grande A, Colonetti T, Della E, da Rosa M . Accuracy of neutrophil gelatinase-associated lipocalin for acute kidney injury diagnosis in children: systematic review and meta-analysis. Pediatr Nephrol. 2017; 32(10):1979-1988. DOI: 10.1007/s00467-017-3704-6. View

12.

Tang T, Lv L, Pan M, Wen Y, Wang B, Li Z . Hydroxychloroquine attenuates renal ischemia/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation. Cell Death Dis. 2018; 9(3):351. PMC: 5834539. DOI: 10.1038/s41419-018-0378-3. View

13.

Han W, Bonventre J . Biologic markers for the early detection of acute kidney injury. Curr Opin Crit Care. 2004; 10(6):476-82. DOI: 10.1097/01.ccx.0000145095.90327.f2. View

14.

Schroder K, Tschopp J . The inflammasomes. Cell. 2010; 140(6):821-32. DOI: 10.1016/j.cell.2010.01.040. View

15.

Fu W, Li B, Wang S, Chen M, Deng R, Ye C . Changes of the tubular markers in type 2 diabetes mellitus with glomerular hyperfiltration. Diabetes Res Clin Pract. 2011; 95(1):105-9. DOI: 10.1016/j.diabres.2011.09.031. View

16.

Basile D, Bonventre J, Mehta R, Nangaku M, Unwin R, Rosner M . Progression after AKI: Understanding Maladaptive Repair Processes to Predict and Identify Therapeutic Treatments. J Am Soc Nephrol. 2015; 27(3):687-97. PMC: 4769207. DOI: 10.1681/ASN.2015030309. View

17.

Salvadori M, Rosso G, Bertoni E . Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. World J Transplant. 2015; 5(2):52-67. PMC: 4478600. DOI: 10.5500/wjt.v5.i2.52. View

18.

Edelstein C . Biomarkers of acute kidney injury. Adv Chronic Kidney Dis. 2008; 15(3):222-34. PMC: 3287955. DOI: 10.1053/j.ackd.2008.04.003. View

19.

Liu S, Chen Y, Wang S, Yu Q . Protective effect of dabrafenib on renal ischemia-reperfusion injury in vivo and in vitro. Biochem Biophys Res Commun. 2019; 522(2):395-401. DOI: 10.1016/j.bbrc.2019.11.105. View

20.

Devarajan P, Mishra J, Supavekin S, Patterson L, Potter S . Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery, and novel therapeutics. Mol Genet Metab. 2003; 80(4):365-76. DOI: 10.1016/j.ymgme.2003.09.012. View