Potential Mechanisms Responsible for the Antinephrolithic Effects of an Aqueous Extract of Fructus Aurantii

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Abstract

The potential effects of Fa extract on the prevention and treatment of CaOx nephrolithiasis were analyzed in an ethylene glycol- (EG-) induced CaOx crystallization model in rats and an in vitro assay. Multiple biochemical variables were measured in the urine and kidney. Kidney sections were subjected to histopathological and immunohistochemical analyses. Urolithiasis-related osteopontin (OPN) was evaluated by Western blotting. The in vitro assay revealed the significant inhibition of crystal formation (3.50 ± 1.43) and dilution of formed crystals (12.20 ± 3.35) in the group treated with 1 mg/mL Fa extract compared with the control group (52.30 ± 4.71 and 53.00 ± 4.54, resp.) ( p < 0.05). The in vivo experiments showed that prophylactic treatment with Fa aqueous extract significantly prevented EG-induced renal crystallization and pathological alterations compared with nephrolithic rats ( p < 0.05). Significantly lower levels of oxidative stress, oxalate, and OPN expression as well as increased citrate and urine output levels were observed in both the low- and high-dose prophylactic groups ( p < 0.05). However, in the low- and high-dose therapeutic groups, none of these indexes were significantly improved ( p > 0.05) except for urinary oxalate in the high-dose therapeutic groups ( p < 0.05). Fa extract prevented CaOx crystallization and promoted crystal dissolution in vitro. Additionally, it was efficacious in preventing the formation of CaOx nephrolithiasis in rats.

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Flavonoids as antioxidants.

Pier-Giorgio Pietta (2000)

Flavonoids are phenolic substances isolated from a wide range of vascular plants, with over 8000 individual compounds known. They act in plants as antioxidants, antimicrobials, photoreceptors, visual attractors, feeding repellants, and for light screening. Many studies have suggested that flavonoids exhibit biological activities, including antiallergenic, antiviral, antiinflammatory, and vasodilating actions. However, most interest has been devoted to the antioxidant activity of flavonoids, which is due to their ability to reduce free radical formation and to scavenge free radicals. The capacity of flavonoids to act as antioxidants in vitro has been the subject of several studies in the past years, and important structure-activity relationships of the antioxidant activity have been established. The antioxidant efficacy of flavonoids in vivo is less documented, presumably because of the limited knowledge on their uptake in humans. Most ingested flavonoids are extensively degraded to various phenolic acids, some of which still possess a radical-scavenging ability. Both the absorbed flavonoids and their metabolites may display an in vivo antioxidant activity, which is evidenced experimentally by the increase of the plasma antioxidant status, the sparing effect on vitamin E of erythrocyte membranes and low-density lipoproteins, and the preservation of erythrocyte membrane polyunsaturated fatty acids. This review presents the current knowledge on structural aspects and in vitro antioxidant capacity of most common flavonoids as well as in vivo antioxidant activity and effects on endogenous antioxidants.

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Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations.

Saeed R Khan (2013)

Idiopathic calcium oxalate kidney stones form while attached to Randall plaques, the subepithelial deposits on renal papillary surfaces. Plaque formation and growth mechanisms are poorly understood. Plaque formation elsewhere in the body is triggered by reactive oxygen species and oxidative stress. This review explores possible reactive oxygen species involvement in plaque formation and calcium oxalate nephrolithiasis. A search of various databases for the last 8 years identified literature on reactive oxygen species involvement in calcium oxalate nephrolithiasis. The literature was reviewed and results are discussed. Under normal conditions reactive oxygen species production is controlled, increasing as needed and regulating crystallization modulator production. Reactive oxygen species overproduction or decreased antioxidants lead to oxidative stress, inflammation and injury, and are involved in stone comorbidity. All major chronic inflammation markers are detectable in stone patient urine. Patients also have increased urinary excretion of the IαI and the thrombin protein families. Results of a recent study of 17,695 participants in NHANES III (National Health and Nutrition Examination Survey) showed significantly lower antioxidants, carotene and β-cryptoxanthin in those with a kidney stone history. Animal model and tissue culture studies revealed that high oxalate, calcium oxalate and calcium phosphate crystals provoked renal cell reactive oxygen species mediated inflammatory responses. Calcium oxalate crystals induce renin up-regulation and angiotensin II generation. Nonphagocytic NADPH oxidase leads to reactive oxygen species production mediated by protein kinase C. The P-38 MAPK/JNK transduction pathway is turned on. Transcriptional and growth factors, and generated secondary mediators become involved. Chemoattractant and osteopontin production is increased and macrophages infiltrate the renal interstitium around the crystal. Phagocytic NADPH oxidase is probably activated, producing additional reactive oxygen species. Localized inflammation, extracellular matrix and fibrosis develop. Crystallization modulators have a significant role in inflammation and tissue repair. Based on available data, Randall plaque formation is similar to extracellular matrix mineralization at many body sites. Renal interstitial collagen becomes mineralized, assisting plaque growth through the interstitium until the mineralizing front reaches papillary surface epithelium. Plaque exposure to pelvic urine may also be a result of reactive oxygen species triggered epithelial sloughing. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study.

L Borghi, T Meschi, F Amato … (1996)

We define the role of urine volume as a stone risk factor in idiopathic calcium stone disease and test the actual preventive effectiveness of a high water intake. We studied 101 controls and 199 patients from the first idiopathic calcium stone episode. After a baseline study period the stone formers were divided by randomization into 2 groups (1 and 2) and they were followed prospectively for 5 years. Followup in group 1 only involved a high intake of water without any dietetic change, while followup in group 2 did not involve any treatment. Each year clinical, laboratory and radiological evaluation was obtained to determine urinary stone risk profile (including relative supersaturations of calcium oxalate, brushite and uric acid by Equil 2), recurrence rate and mean time to relapse. The original urine volume was lower in male and female stone formers compared to controls (men with calcium oxalate stones 1,057 +/- 238 ml./24 hours versus normal men 1,401 +/- 562 ml./24 hours, p < 0.0001 and women calcium oxalate stones 990 +/- 230 ml./24 hours versus normal women 1,239 +/- 440 ml./24 hours, p < 0.001). During followup recurrences were noted within 5 years in 12 of 99 group 1 patients and in 27 of 100 group 2 patients (p = 0.008). The average interval for recurrences was 38.7 +/- 13.2 months in group 1 and 25.1 +/- 16.4 months in group 2 (p = 0.016). The relative supersaturations for calcium oxalate, brushite and uric acid were much greater in baseline urine of the stone patients in both groups compared to controls. During followup, baseline values decreased sharply only in group 1. Finally the baseline urine in patients with recurrences was characterized by a higher calcium excretion compared to urine of the patients without recurrences in both groups. We conclude that urine volume is a real stone risk factor in nephrolithiasis and that a large intake of water is the initial therapy for prevention of stone recurrences. In cases of hypercalciuria it is suitable to prescribe adjuvant specific diets or drug therapy.

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Author and article information

Journal

Journal ID (nlm-ta): Evid Based Complement Alternat Med

Journal ID (iso-abbrev): Evid Based Complement Alternat Med

Journal ID (publisher-id): ECAM

Title: Evidence-based Complementary and Alternative Medicine : eCAM

Publisher: Hindawi Publishing Corporation

ISSN (Print): 1741-427X

ISSN (Electronic): 1741-4288

Publication date (Print): 2015

Publication date (Electronic): 15 June 2015

Publication date PMC-release: 15 June 2015

Volume: 2015

Electronic Location Identifier: 491409

Affiliations

¹Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China

²Department of Neurosurgery, The Neurosurgery Clinical Medical Center, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China

Author notes

*Zhongjin Yue: yuezhongjinlz@ 123456126.com

Academic Editor: Armando Zarrelli

Article

DOI: 10.1155/2015/491409

PMC ID: 4485555

PubMed ID: 26170875

SO-VID: d2a7d976-9c59-4812-bce6-bc30c5ea5154

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 7 January 2015

Date revision received : 5 May 2015

Date accepted : 5 May 2015

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Potential Mechanisms Responsible for the Antinephrolithic Effects of an Aqueous Extract of Fructus Aurantii

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Most cited references 45

Flavonoids as antioxidants.

Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations.

Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study.

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