Citrate Attenuates Adenine-Induced Chronic Renal Failure in Rats by Modulating the Th17/Treg Cell Balance

Ou, Yan; Li, Shuiqin; Zhu, Xiaojing; Gui, Bao‐Song; Yao, Guangqing; Ma, Liqun; Zhu, Dan; Fu, Rongguo; Ge, Heng; Wang, Li; Jia, Lining; Tian, Liang; Duan, Zhaoyang

doi:10.1007/s10753-015-0225-y

Cited by 12 publications

(11 citation statements)

References 33 publications

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“…Interestingly, citrate has also been associated with immunomodulatory effects. In AKI patients with continuous venovenous hemofiltration therapy, citrate administration reduces myeloperoxidase and interleukin 8 (IL-8) plasma levels [ 58 ]; in a model of CKD induced by adenine in rats, the administration of citrate reduces the production of pro-inflammatory cytokines interleukin 6 (IL-6) and interleukin 17 (IL-17), whereas it increases the anti-inflammatory cytokines interleukin 10 (IL-10) and TGF-β [ 59 ].…”

Section: Citratementioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.

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Section: Citratementioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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“…For example, citrate inhibits urinary stones by reduced calcium stone formation in human . Our former study demonstrates that citrates influence the endoplasmic reticulum stress and immune system in the rat model of CRF . However, there has been no study about the effect of citrate on VC in CRF.…”

Section: Discussionmentioning

confidence: 91%

Citrate attenuates vascular calcification in chronic renal failure rats

Liu

et al. 2017

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Vascular calcification (VC) is a major contributor of cardiovascular dysfunction in chronic renal failure (CRF). Citrate binds calcium and inhibits the growth of calcium crystals. This present study intends to evaluate the effect of citrate on VC in adenine-induced CRF rats. The rats were randomly divided into five groups: the control group, the citrate control group, model group, model rats with low-dose treatment of citrate (216 mg/kg) and model rats with high-dose treatment of citrate (746 mg/kg). The rats were euthanized at 5 weeks with their blood and aorta in detection. The results showed that serum level of blood urea nitrogen, serum creatinine, phosphorus, calcium, and related renal failure function marker were elevated in the model group. Furthermore, the aortic calcium accumulation and alkaline phosphatase activity were significantly increased in the model group compared with control groups. Additionally, hematoxylin-eosin staining results demonstrated that the vascular calcification in aorta is significantly increased in the model group. Finally, the expression of VC-related proteins including bone morphogenetic protein and osteocalcin were increased in the model group, whereas alpha-smooth muscle actin was decreased in the model group compared with the control group. However, treatment with citrate caused a reversal effect of all the above events in a dose-dependent manner. In conclusion, citrate may attenuate vascular calcification in adenine-induced CRF rats.

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“…α-ketoglutaric acid (AKG) is a key metabolite in the TCA cycle ( 21 ) that can restore the antioxidant status of the organ, reduce the mitochondrial structural changes, decrease adenosine triphosphate (ATP) levels in the proximal kidney tubule under hypoxia, partially restore ATP levels by supplementing the TCA circulation, and reduce kidney dysfunction ( 22 , 23 ). The role of citrate in kidney disease includes immunomodulatory effects, the regulation of acetyl-CoA synthesis, and even its use as an anticoagulant during kidney replacement therapy in acute kidney injury (AKI) and chronic kidney disease (CKD) ( 24 , 25 ). Malate is an intermediate in the citric acid cycle, and increased malate activity has been reported in cisplatin-induced kidney dysfunction that may be a repair mechanism for malate ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis

Jiao

et al. 2022

Front. Endocrinol.

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Kidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum biochemistry and kidney histopathology of male Kunming mice aged 3 months and 24 months and found that the aged mice had inflammatory lesions, aggravated fibrosis, and functional impairment. A high-resolution untargeted metabolomics analysis revealed that the endogenous metabolites in the kidneys and urine of the mice were significantly changed by 25 and 20 metabolites, respectively. A pathway analysis of these differential metabolites revealed six key signaling pathways, namely, D-glutamine and D-glutamate metabolism, purine metabolism, the citrate cycle [tricarboxylic acid (TCA) cycle], histidine metabolism, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism. These pathways are involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism, and these can lead to immune regulation, inflammatory responses, oxidative stress damage, cellular dysfunction, and bioenergy disorders, and they are closely associated with aging and kidney insufficiency. We also screened nine types of sensitive metabolites in the urine as potential biomarkers of kidney dysfunction during the aging process to confirm their therapeutic targets in senior-induced kidney dysfunction and to improve the level of risk assessment for senile kidney injury.

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Citrate Attenuates Adenine-Induced Chronic Renal Failure in Rats by Modulating the Th17/Treg Cell Balance

Cited by 12 publications

References 33 publications

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Citrate attenuates vascular calcification in chronic renal failure rats

Changes in aging-induced kidney dysfunction in mice based on a metabolomics analysis

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