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      Siwu Granules and Erythropoietin Synergistically Ameliorated Anemia in Adenine-Induced Chronic Renal Failure Rats

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          Abstract

          Objective

          Renal anemia in patients with end-stage chronic kidney disease is closely related to the deterioration of cardiac function, renal function, and quality of life. This study involved adenine-induced renal anemic rat models and evaluated the treatment effect of Siwu granules and/or erythropoietin (EPO).

          Methods

          Fifty SD rats were randomly divided into 5 groups: control, model, Siwu, EPO, and Siwu plus EPO groups. The expression levels of NO, MDA, SOD, CAT, IL-6, TNF- α, EPO, EPOR, α-SMA, and TGF- β1 were detected in rats after 8 weeks of treatment with Siwu granules and/or EPO.

          Results

          After modeling, 47 rats entered the stage of treatment. Siwu plus EPO treatment significantly increased the rat hemoglobin content ( p < 0.05) and reduced blood urea nitrogen ( p < 0.05) and serum creatinine ( p < 0.001). Compared with the control group, the expression of EPO and EPOR in the kidney of rats with renal failure was significantly decreased ( p < 0.05). Moreover, the Siwu plus EPO group improved the level of oxidative stress in rats with chronic renal failure and reduced the expression of inflammatory factors. The expression of α-SMA and TGF- β1 in rats with renal failure was higher, but there was no expression in the control group.

          Conclusion

          Combined treatment of Siwu granules with EPO increased the expression of EPO and EPOR in the renal tissues and inhibited oxidative stress and inflammatory factors, improving the renal function and anemia.

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          Most cited references38

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          Mechanisms of anemia in CKD.

          Jodie L. Babitt, Herbert Y. Lin (2012)
          Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia.
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            Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice.

            Ken-ichi Yamamura, Takeshi Kimura, Jin Nakamura … (2011)
            In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced production of fibroblast-derived erythropoietin, a hormone that stimulates erythropoiesis. Despite their importance in chronic kidney disease, the origin and regulatory mechanism of fibroblasts remain unclear. Here, we have demonstrated that the majority of erythropoietin-producing fibroblasts in the healthy kidney originate from myelin protein zero-Cre (P0-Cre) lineage-labeled extrarenal cells, which enter the embryonic kidney at E13.5. In the diseased kidney, P0-Cre lineage-labeled fibroblasts, but not fibroblasts derived from injured tubular epithelial cells through epithelial-mesenchymal transition, transdifferentiated into myofibroblasts and predominantly contributed to fibrosis, with concomitant loss of erythropoietin production. We further demonstrated that attenuated erythropoietin production in transdifferentiated myofibroblasts was restored by the administration of neuroprotective agents, such as dexamethasone and neurotrophins. Moreover, the in vivo administration of tamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well as fibrosis in a mouse model of kidney fibrosis. These findings reveal the pathophysiological roles of P0-Cre lineage-labeled fibroblasts in the kidney and clarify the link between renal fibrosis and renal anemia.
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              Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

              Yuanyuan Zhang, Li-Li Wang, Soumyadeep Dey … (2014)
              Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease.
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                Author and article information

                Contributors
                Jiandong Gao:
                ORCID: https://orcid.org/0000-0002-1645-837X
                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
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date Collection: 2019
                Publication date (Electronic): 14 December 2019
                Publication date PMC-release: 14 December 2019
                Volume: 2019
                Electronic Location Identifier: 5832105
                Affiliations
                1Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (14DZ2273200), Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, No. 528 Road ZhangHeng, Shanghai 201203, China
                2Department of Internal Medicine, Shanghai TCM-Integrated Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine, No. 184 Road BaoDing, Shanghai 200082, China
                3Department of Nephrology, Traditional Chinese Medicine Hospital of Langfang City, No. 108 Road North Yinhe, Langfang 065000, China
                4Department of Nephrology, Xiamen Hospital of Traditional Chinese Medicine, No. 1739 Road Xianyue, Xiamen 361009, China
                Author notes

                Academic Editor: Francisco Solano

                Author information
                https://orcid.org/0000-0002-1645-837X
                Article
                DOI: 10.1155/2019/5832105
                PMC ID: 6931032
                SO-VID: 618a5732-7bf2-492e-8743-2af0f1dec244
                Copyright © Copyright © 2019 Yansheng Wu et al.
                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 : 16 July 2019
                Date revision received : 19 October 2019
                Date accepted : 2 November 2019
                Funding
                Funded by: Shanghai University of Traditional Chinese Medicine
                Award ID: 2015YCX18
                Funded by: National Natural Science Foundation of China
                Award ID: 81373613
                Funded by: Shanghai Municipal Key Laboratory of Clinical Medicine
                Award ID: 14DZ2273200
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Complementary & Alternative medicine
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine

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