scholarly journals Lactiplantibacillus plantarum Reduced Renal Calcium Oxalate Stones by Regulating Arginine Metabolism in Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Liu ◽  
Xi Jin ◽  
Lei Tian ◽  
Zhongyu Jian ◽  
Yucheng Ma ◽  
...  

Renal calcium oxalate (CaOx) stones are a common kidney disease. There are few methods for reducing the formation of these stones. However, the potential of probiotics for reducing renal stones has received increasing interest. We previously isolated a strain of Lactiplantibacillus plantarum N-1 from traditional cheese in China. This study aimed to investigate the effects of N-1 on renal CaOx crystal deposition. Thirty rats were randomly allocated to three groups: control group (ddH2O by gavage), model group [ddH2O by gavage and 1% ethylene glycol (EG) in drinking water], and Lactiplantibacillus group (N-1 by gavage and 1% EG in drinking water). After 4 weeks, compared with the model group, the group treated with N-1 exhibited significantly reduced renal crystals (P < 0.05). In the ileum and caecum, the relative abundances of Lactobacillus and Eubacterium ventriosum were higher in the control group, and those of Ruminococcaceae UCG 007 and Rikenellaceae RC9 were higher in the N-1-supplemented group. In contrast, the relative abundances of Staphylococcus, Corynebacterium 1, Jeotgalicoccus, Psychrobacter, and Aerococcus were higher in the model group. We also predicted that the arginase level would be higher in the ileal microbiota of the model group than in the N-1-supplemented group with PICRUSt2. The arginase activity was higher, while the level of arginine was lower in the ileal contents of the model group than in the N-1-supplemented group. The arginine level in the blood was also higher in the N-1-supplemented group than in the model group. In vitro studies showed that exposure to arginine could reduce CaOx crystal adhesion to renal epithelial HK-2 cells. Our findings highlighted the important role of N-1 in reducing renal CaOx crystals by regulating arginine metabolism in the gut microbiota. Probiotics containing L. plantarum N-1 may be potential therapies for preventing renal CaOx stones.

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Wei Zhu ◽  
Zhijian Zhao ◽  
Fu-Ju Chou ◽  
Li Zuo ◽  
Tongzu Liu ◽  
...  

Females develop kidney stones less frequently than males do. However, it is unclear if this gender difference is related to altered estrogen/estrogen receptor (ER) signaling. Here, we found that ER beta (ERβ) signals could suppress hepatic oxalate biosynthesis via transcriptional upregulation of the glyoxylate aminotransferase (AGT1) expression. Results from multiple in vitro renal cell lines also found that ERβ could function via suppressing the oxalate-induced injury through increasing the reactive oxygen species (ROS) production that led to a decrease of the renal calcium oxalate (CaOx) crystal deposition. Mechanism study results showed that ERβ suppressed oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) through direct binding to the estrogen response elements (EREs) on the NOX2 5′ promoter. We further applied two in vivo mouse models with glyoxylate-induced renal CaOx crystal deposition and one rat model with 5% hydroxyl-L-proline-induced renal CaOx crystal deposition. Our data demonstrated that mice lacking ERβ (ERβKO) as well as mice or rats treated with ERβ antagonist PHTPP had increased renal CaOx crystal deposition with increased urinary oxalate excretion and renal ROS production. Importantly, targeting ERβ-regulated NOX2 with the NADPH oxidase inhibitor, apocynin, can suppress the renal CaOx crystal deposition in the in vivo mouse model. Together, results from multiple in vitro cell lines and in vivo mouse/rat models all demonstrate that ERβ may protect against renal CaOx crystal deposition via inhibiting the hepatic oxalate biosynthesis and oxidative stress-induced renal injury.


2009 ◽  
Vol 296 (1) ◽  
pp. F34-F45 ◽  
Author(s):  
Ho-Shiang Huang ◽  
Ming-Chieh Ma ◽  
Jun Chen

Vitamin E was previously reported to reduce calcium oxalate (CaOx) crystal formation. This study explored whether vitamin E deficiency affects intrarenal oxidative stress and accelerates crystal deposition in hyperoxaluria. The control (C) group of rats received a standard diet and drinking water, while the experimental groups received 0.75% ethylene glycol (EG) in drinking water for 42 days. Of the latter, one group received a standard diet (EG group), one received a low-vitamin E (LE) diet (EG+LE group), and the last received an LE diet with vitamin E supplement (4 mg) (EG+LE+E group). The C+LE and C+LE+E groups were the specific controls for the last two experimental groups, respectively. In a separate experiment, EG and EG+LE rats were studied on days 3–42 to examine the temporal relationship between oxidative change and crystal formation. Urinary biochemistry and activity/levels of antioxidative and oxidative enzymes in glomeruli and tubulointerstitial specimens (TIS) were examined. In EG rats, CaOx crystal accumulation was associated with low antioxidative enzyme activity in TIS and with increased oxidative enzyme expression in glomeruli. In the EG+LE group, marked changes in antioxidative and oxidative enzyme levels were seen and correlated with massive CaOx deposition and tubular damage. The increased oxidative stress seen with EG+LE treatment was largely reversed by vitamin E supplementation. A temporal study showed that decrease in antioxidative defense and increased free radical formation in the EG+LE group occurred before crystal deposition. This study shows that low vitamin E disrupts the redox balance and causes cell death, thereby favoring crystal formation.


Author(s):  
Ya-Xin Zhang ◽  
Shan-Shan Qu ◽  
Li-Hua Zhang ◽  
Yu-Yan Gu ◽  
Yi-Hao Chen ◽  
...  

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.


2020 ◽  
Vol 4 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Falah M. Aziz ◽  
Dlshad H. Hassan

Urolithiasis is a well-known problem that stones could form in various parts of the urinary system and it is the most common disease of the urinary tract. The current study was planned to investigate the effect of radish juice on ethylene glycol (EG)-induced urolithiasis. Twenty-one rats randomly divided into three groups. The first group was the control group was received normal standard diet and drinking water and the second group represented the model group received 0.75% EG in drinking water ad libitum. The third group received radish juice (2 ml/kg of body weight) by gavage plus EG (0.75%) in drinking water ad libitum. The experiment was conducted for 28 days. The light microscope examination revealed a disturbed histological architecture of the kidney tissues, including dilated renal tubules, aggregation of infiltrated leukocytes inflammatory cells, and crystal deposition in the model group. The EG plus radish juice treated rats showed higher crystal density with improved renal tubule structure and alleviated inflammation. Both treated groups showed various biochemical alterations compared to control group, but the most interest biochemical result was the significant decrease of malondialdehyde, a lipid peroxidation marker, and in the radish plus EG group compared to the EG group. Scanning electron microscopy showed clear structural detail about calcium oxalate crystals in which radish-treated group showed higher crystal deposition and calcified tissue compared to EG group. The present study concluded that radish juice promotes stone deposition but exerted an antioxidant effect.


2020 ◽  
Vol 134 (19) ◽  
pp. 2565-2580
Author(s):  
Yi-Shiou Tseng ◽  
Wen-Bin Wu ◽  
Yun Chen ◽  
Feili Lo Yang ◽  
Ming-Chieh Ma

Abstract Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism is unclear. Here, we examined how SB affected renal oxalate and citrate handlings for in vivo hyperoxaluric rats and in vitro tubular cells. SB was induced by small intestine resection in male Wistar rats. Sham-operated controls had no resection. After 7 days of recovery, the rats were divided into control, SB (both fed with distilled water), ethylene glycol (EG), and SB+EG (both fed with 0.75% EG for hyperoxaluric induction) groups for 28 days. We collected the plasma, 24 h of urine, kidney, and intestine tissues for analysis. Hypocitraturia was found and persisted up to 28 days for the SB group. Hypocalcemia and high plasma parathyroid hormone (PTH) levels were found in the 28-day SB rats. SB aggravated EG-mediated oxalate nephropathy by fostering hyperoxaluria and hypocitraturia, and increasing the degree of supersaturation and calcium oxalate (CaOx) crystal deposition. These effects were associated with renal up-regulations of the oxalate transporter solute carrier family 26 (Slc26)a6 and citrate transporter sodium-dependent dicarboxylate cotransporter-1 (NaDC-1) but not Slc26a2. The effects of PTH on the SB kidneys were then examined in NRK-52E tubular cells. Recombinant PTH attenuated oxalate-mediated cell injury and up-regulated NaDC-1 via protein kinase A (PKA) activation. PTH, however, showed no additive effects on oxalate-induced Slc26a6 and NaDC-1 up-regulation. Together, these results demonstrated that renal NaDC-1 upregulation-induced hypocitraturia weakened the defense against Slc26a6-mediated hyperoxaluria in SB kidneys for excess CaOx crystal formation. Increased tubular NaDC-1 expression caused by SB relied on PTH.


2018 ◽  
Vol 51 (1) ◽  
pp. 441-451 ◽  
Author(s):  
Gang Liu ◽  
Wenxin Yan ◽  
Sujuan  Ding ◽  
Hongmei Jiang ◽  
Yong Ma ◽  
...  

Background/Aims: There are known links between inflammatory bowel disease (IBD) and changes in the microbiota of the gut and inflammation and oxidative stress. In this study, a colitis model induced by dextran sodium sulfate (DSS) in mice is used to evaluate whether the presence of bioactive peptides IRW (Ile-Arg-Trp) and IQW (Ile-Gln-Trp) peptides is advantageous. Methods: The mice were arbitrarily assigned to the following four groups: (i) control (untreated), (ii) dextran sodium sulfate (DSS) treated, (iii) IRW-DSS treated, and (iv) IQW-DSS treated. For 7 days, the control group subjects had unrestricted access to untreated drinking water, whereas the drinking water supplied to the subjects in the DSS, IRW-DSS, and IQW-DSS groups during this period consisted of 5% DSS solution. The colonic lesions were scored after hematoxylin and eosin staining. Serum antioxidant capacity was analyzed by 2,2’-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical cation decolorization test and the microbiota in the colonic contents were sequenced by HiSeq2500 PE250. Results: The presence of DSS reduced daily weight gain, enhanced histopathology scores, and inhibited antioxidant enzyme expression. Superoxide dismutase, catalase, and glutathione peroxidase activities in the DSS-induced colitis model were significantly enhanced (P < 0.05) in the presence of dietary IRW and IQW. Furthermore, the Simpson index was significantly increased (P < 0.05) in the presence of dietary IRW and IQW compared to the control group. IRW and IQW increased the abundance of Coprococcus_1, Ruminococcaceae_UCG-014, and Desulfovibrio compared to the control group and DSS group. Furthermore, IQW decreased the abundance of Bacteroides in relation to the control group, but increased Parabacteroides. In addition, IRW increased the level of Anaerotruncus, Oscillibacter, and Ruminiclostridium_9 compared to the control group. Conclusion: This study concludes that the presence of IRW or IQW can mitigate DSS-induced oxidative stress by improving the activities of antioxidant enzymes, increasing intestinal microbial diversity and enhancing the abundance of gut microbiota, which may help maintain the homeostasis of host health and microenvironment in a DSS-induced mouse model, thus providing a potential further treatment for IBD patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Chen ◽  
Yachen Si ◽  
Jin Cheng ◽  
Jiarong Ding ◽  
Hongxia Zhao ◽  
...  

Grona styracifolia (Osbeck) Merr. (GS), a popular folk medicine, is clinically applied to treat nephrolithiasis. In this study, a urinary metabolic analysis was performed in a mouse model of renal calcium oxalate (CaOx) crystal deposition to identify the differentially altered metabolites in mice with oxalate-induced renal injury and explore the therapeutic mechanisms of GS against nephrolithiasis. Twenty-four mice were randomly divided into the control, oxalate and GS-treated groups. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to analyze the metabolic profiles of the urine samples. In addition, network pharmacology analysis was performed with different databases. As a result, the protective effects of GS were verified by measuring biochemical parameters and detecting crystal deposition. Fifteen metabolites were identified as the differentially altered metabolites in mice with crystal-induced renal injury. Most were involved in amino acid and fatty acid metabolism. Thirteen of these metabolites showed a reversal trend following GS treatment. A component-target-metabolite network was further constructed and nine overlapping target proteins of GS and the differentially altered metabolites were discovered. Among these proteins, the expression of estrogen receptor 2 (ESR2) in renal tissues was significantly down-regulated while androgen receptor (AR) expression was obviously increased in the oxalate group compared with the control group. These changes were reversed by the GS treatment. In conclusion, GS exerts its therapeutic effect by regulating multiple metabolic pathways and the expression of ESR and AR in mice with oxalate-induced renal injury.


2020 ◽  
Author(s):  
Haoqing Shao ◽  
Chenyang Zhang ◽  
Nenqun Xiao ◽  
Zhoujin Tan

Abstract Background: Antibiotic-associated diarrhea (AAD), defined as diarrhea that occurs in association with the administration of antibiotics and without another clear etiology, is one of the most commonly adverse drug events of antibiotics therapy. We established a diarrhea model induced by gentamycin and cefradine to investigate the microbiota characteristics in the intestinal lumen of mice with AAD and provide insights into noteworthy bacteria related to gentamicin and cefradine-associated diarrhea.Results: The number of OTUs in the model group and the normal group was 983 and 2107, respectively, and 872 identical OTUs were shared between two groups. Species richness and species diversity of intestinal microbe were altered by antibiotics administration. The dominant phyla of AAD mice were Firmicutes (52.63%) and Proteobacteria (46.37%). The abundance of 8 genera, Ruminococcus, Blautia, Enterococcus, Eubacterium, Clostridium, Coprococcus, Aerococcus, and Pseudomonas, increased significantly, and the abundance of 3 genera, Prevotella, Bacteroides, and Adlercreutzia, decreased significantly in the model group compared to those in the control group (p < 0.05). LEfSe analysis showed that Enterococcus, Eubacterium, Ruminococcus, and Blautia were the key differential genera in the model group.Conclusions: The bacterial diversity of the intestinal lumen was diminished after gentamicin and cefradine administration. The alterations in the abundance and composition of gut microbiota further led to the dysfunction of gut microbiota. More specifically, gentamicin and cefradine significantly increased the abundance of the opportunistic pathogens, of which Enterococcus and Clostridium were the most prominent and most worthy of attention.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Peng Lv ◽  
Haoran Liu ◽  
Tao Ye ◽  
Xiaoqi Yang ◽  
Chen Duan ◽  
...  

The roles of the lncRNA X inactive specific transcript (XIST) in many diseases, including cancers and inflammatory sickness, have been previously elucidated. However, renal calculus remained poorly understood. In this study, we revealed the potential effects of XIST on kidney stones that were exerted via inflammatory response and oxidative stress mechanisms. We established a glyoxylate-induced calcium oxalate (CaOx) stone mouse model and exposed HK-2 cells to calcium oxalate monohydrate (COM). The interactions among XIST, miR-223-3p, and NOD-like receptor protein 3 (NLRP3) and their respective effects were determined by RNAs and protein expression, luciferase activity, and immunohistochemistry (IHC) assays. Cell necrosis, reactive oxygen species (ROS) generation, and inflammatory responses were detected after silencing XIST, activating and inhibiting miR-223-3p, and both knocking down XIST and activating miR-223-3p in vitro and in vivo. The XIST, NLRP3, caspase-1, and IL-1β levels were notably increased in kidney samples from glyoxylate-induced CaOx stone model mice. XIST knockdown significantly suppressed the inflammatory damage and ROS production and further attenuated oxalate crystal deposition. miRNA-223-3p mimics also exerted the same effects. Moreover, we verified the interactions among XIST, miRNA-223-3p and NLRP3, and the subsequent effects. Our results suggest that the lncRNA XIST participates in the formation and progression of renal calculus by interacting with miR-223-3p and the NLRP3/Caspase-1/IL-1β pathway to mediate the inflammatory response and ROS production.


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