Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Intensive Care
Published in: Annals of Intensive Care 1/2017

Open Access 01-12-2017 | Research

Astragaloside-IV prevents acute kidney injury and inflammation by normalizing muscular mitochondrial function associated with a nitric oxide protective mechanism in crush syndrome rats

Authors: Isamu Murata, Yuji Abe, Yuka Yaginuma, Kayako Yodo, Yuka Kamakari, Yurika Miyazaki, Daichi Baba, Yuko Shinoda, Toru Iwasaki, Kunihiko Takahashi, Jun Kobayashi, Yutaka Inoue, Ikuo Kanamoto

Published in: Annals of Intensive Care | Issue 1/2017

Login to get access

Abstract

Background

Crush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from decompression after compression (i.e., ischemia/reperfusion injury). A large number of CS patients develop cardiac failure, kidney dysfunction, and systemic inflammation, even when fluid therapy is administered. We evaluated whether the administration of astragaloside-IV (AS)-containing fluid improved survival by preventing kidney and muscular mitochondrial dysfunction in a rat model of CS.

Results

The CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into four groups: (1) sham; (2) CS with no treatment; (3) CS with normal saline treatment; and (4) CS with normal saline + 10 mg/kg AS. AS-containing fluid improved kidney function by improving shock and metabolic acidosis in CS rats. In addition, there was a reduction in oxidative damage. The attenuation of hyperkalemia was significantly related to improving muscle injury via preventing mitochondrial dysfunction. Moreover, this mitochondria protection mechanism was related to the nitric oxide (NO) generated by activation of endothelial nitric oxide synthase, which provided an anti-oxidative and anti-inflammatory effect.

Conclusions

Treatment with AS-containing fluid led to a dramatic improvement in survival following CS because of direct and indirect anti-oxidative effects in the kidney, and improvements in mitochondrial dysfunction and inflammation owing to AS acting as an NO donor in injured muscle.
Appendix
Available only for authorised users
Literature
1.
Smith J, Greaves I. Crush injury and crush syndrome: a review. J Trauma. 2003;54:S226–30.PubMed
2.
Sever MS, Vanholder R, Ashkenazi I, Becker G, Better O, Covic A, et al. Recommendation for the management of crush victims in mass disasters. Nephrol Dial Transpl. 2012;27:i1–67.CrossRef
3.
4.
Chen XJ, Meng D, Feng L, Bian YY, Li P, Yang D, et al. Protective effect of astragalosides on myocardial injury by isoproterenol in SD rats. Am J Chin Med. 2006;34:1015–25.CrossRefPubMed
5.
Li ZP, Cao Q. Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats. Acta Pharmacol Sin. 2002;23:898–904.PubMed
6.
Qu YZ, Li M, Zhao YL, Zhao ZW, Wei XY, Liu JP, et al. Astragaloside IV attenuates cerebral ischemia–reperfusion-induced increase in permeability of the blood-brain barrier in rats. Eur J Pharmacol. 2009;606:137–41.CrossRefPubMed
7.
Zhang WD, Chen H, Zhang C, Liu RH, Li HL, Chen HZ. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro. Planta Med. 2006;72:4–8.CrossRefPubMed
8.
Tan S, Wang G, Guo Y, Gui D, Wang N. Preventive effects of a natural anti-inflammatory agent, astragaloside IV, on ischemic acute kidney injury in rats. Evid Based Complement Altern Med. 2013;. doi:10.​1155/​2013/​284025.
9.
Qi W, Niu J, Qin Q, Qiao Z, Gu Y. Astragaloside IV attenuates glycated albumin-induced epithelial-to-mesenchymal transition by inhibiting oxidative stress in renal proximal tubular cells. Cell Stress Chaperones. 2014;19:105–14.CrossRefPubMed
10.
Murata I, Ooi K, Shoji S, Motohashi Y, Kan M, Ohtake K, et al. Acute lethal crush-injured rats can be successfully rescued by a single injection of high-dose dexamethasone through a pathway involving PI3K-Akt-eNOS signaling. J Trauma Acute Care Surg. 2013;75:241–9.CrossRefPubMed
11.
Murata I, Miyake Y, Takahashi N, Suzuki R, Fujiwara T, Sato Y, et al. Low-dose sodium nitrite fluid resuscitation prevents lethality from crush syndrome by improving nitric oxide consumption and preventing myoglobin cytotoxicity in kidney in a rat model. Shock. 2017;48:112–8.CrossRefPubMed
12.
Murata I, Ooi K, Sasaki H, Kimura S, Ohtake K, Ueda H, et al. Characterization of systemic and histologic injury after crush syndrome and intervals of reperfusion in a small animal model. J Trauma. 2011;70:1453–63.CrossRefPubMed
13.
Huang XP, Tan H, Chen BY, Deng CQ. Astragalus extract alleviates nerve injury after cerebral ischemia by improving energy metabolism and inhibiting apoptosis. Biol Pharm Bull. 2012;35:449–54.CrossRefPubMed
14.
Sharma OP, Bhat TK. DPPH antioxidant assay revisited. Food Chem. 2009;113:1202–5.CrossRef
15.
Li M, Qu YZ, Zhao ZW, Wu SX, Liu YY, Wei XY, et al. Astragaloside IV protects against focal cerebral ischemia/reperfusion injury correlating to suppression of neutrophils adhesion-related molecules. Neurochem Int. 2012;60:458–65.CrossRefPubMed
16.
Murata I, Nozaki R, Ooi K, Ohtake K, Kimura S, Ueda H, et al. Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model. J Trauma Acute Care Surg. 2012;72:1548–54.CrossRefPubMed
17.
Obialo CI, Okonofua EC, Nzerue MC, Tayade AS, Riley LJ. Role of hypoalbuminemia and hypocholesterolemia as copredictors of mortality in acute renal failure. Kidney Int. 1999;56:1058–63.CrossRefPubMed
18.
Bullock ML, Umen AJ, Finkelstein M, Keane WF. The assessment of risk factors in 462 patients with acute renal failure. Am J Kidney Dis. 1985;5:97–103.CrossRefPubMed
19.
Sever MS, Erek E, Vanholder R, Koc M, Yavuz M, Aysuna N, et al. Lessons learned from the catastrophic Marmara earthquake: factors influencing the final outcome of renal victims. Clin Nephrol. 2004;61:413–21.CrossRefPubMed
20.
Chertow GM, Christiansen CL, Cleary PD, Munro C, Lazarus JM. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med. 1995;155:1505–11.CrossRefPubMed
21.
Better OS, Rubinstein I. Management of shock and acute renal failure in casualties suffering from the crush syndrome. Ren Fail. 1997;19:647–53.CrossRefPubMed
22.
23.
Better OS. Traumatic rhabdomyolysis (“crush syndrome”)—updated 1989. Isr J Med Sci. 1989;25:69–72.PubMed
24.
Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol. 2000;8:72–6.CrossRefPubMed
25.
Moore KP, Holt SG, Patel RP, Svistunenko DA, Zackert W, Goodier D, et al. A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure. J Biol Chem. 1998;273:31731–7.CrossRefPubMed
26.
Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med. 2006;354:1052–63.CrossRefPubMed
27.
Hashimoto R, Adachi H, Nishida H, Tsuruta M, Nomura G. Serum N-acetyl-beta-d-glucosaminidase activity in predicting the development of hypertension. Hypertension. 1995;25:1311–4.CrossRefPubMed
28.
Ashkenazi I, Isakovich B, Kluger Y, Alfici R, Kessel B, Better OS. Prehospital management of earthquake casualties buried under rubble. Prehosp Disaster Med. 2005;20:122–33.CrossRefPubMed
29.
Wink DA, Miranda KM, Espey MG, Pluta RM, Hewett SJ, Colton C, et al. Mechanisms of the antioxidant effects of nitric oxide. Antioxid Redox Signal. 2001;3:203–13.CrossRefPubMed
30.
31.
Khan BV, Harrison DG, Olbrych MT, Alexander RW, Medford RM. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA. 1996;93:9114–9.CrossRefPubMedPubMedCentral
32.
Guner S, Oncu MR. Evaluation of crush syndrome patients with extremity injuries in the 2011 Van Earthquake in Turkey. J Clin Nurs. 2014;23:243–9.CrossRefPubMed
33.
Murata I, Goto M, Komiya M, Motohashi R, Hirata M, Inoue Y, et al. Early therapeutic intervention for crush syndrome: characterization of intramuscular administration of dexamethasone by pharmacokinetic and biochemical parameters in rats. Biol Pharm Bull. 2016;39:1424–31.CrossRefPubMed
Metadata
Title
Astragaloside-IV prevents acute kidney injury and inflammation by normalizing muscular mitochondrial function associated with a nitric oxide protective mechanism in crush syndrome rats
Authors
Isamu Murata
Yuji Abe
Yuka Yaginuma
Kayako Yodo
Yuka Kamakari
Yurika Miyazaki
Daichi Baba
Yuko Shinoda
Toru Iwasaki
Kunihiko Takahashi
Jun Kobayashi
Yutaka Inoue
Ikuo Kanamoto
Publication date
01-12-2017
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2017
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-017-0313-2

Other articles of this Issue 1/2017

Annals of Intensive Care 1/2017 Go to the issue

Research

Protective effect of early low-dose hydrocortisone on ventilator-associated pneumonia in the cancer patients: a propensity score analysis

Research

Dynamic driving pressure associated mortality in acute respiratory distress syndrome with extracorporeal membrane oxygenation

Review

Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients?

Research

Seawater drowning-associated pneumonia: a 10-year descriptive cohort in intensive care unit

Research

Does metformin exposure before ICU stay have any impact on patients’ outcome? A retrospective cohort study of diabetic patients

Research

Anemia at pediatric intensive care unit discharge: prevalence and risk markers