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. 2021 Mar 7;13(3):192.
doi: 10.3390/toxins13030192.

The Administration of the Synbiotic Lactobacillus bulgaricus 6c3 Strain, Inulin and Fructooligosaccharide Decreases the Concentrations of Indoxyl Sulfate and Kidney Damage in a Rat Model

Alonso Jerez-Morales  1   2 , José S Merino  3 , Sindy T Díaz-Castillo  2 , Carlos T Smith  1 , Jorge Fuentealba  4 , Humberto Bernasconi  2 , Gerson Echeverría  5 , Apolinaria García-Cancino  1
Affiliations

The Administration of the Synbiotic Lactobacillus bulgaricus 6c3 Strain, Inulin and Fructooligosaccharide Decreases the Concentrations of Indoxyl Sulfate and Kidney Damage in a Rat Model

Alonso Jerez-Morales et al. Toxins (Basel). .

Abstract

Indoxyl sulfate (IS) is involved in the progression of chronic kidney disease (CKD) and in its cardiovascular complications. One of the approaches proposed to decrease IS is the administration of synbiotics. This work aimed to search for a probiotic strain capable to decrease serum IS levels and mix it with two prebiotics (inulin and fructooligosaccharide (FOS)) to produce a putative synbiotic and test it in a rat CKD model. Two groups of Sprague-Dawley rats were nephrectomized. One group (Lac) received the mixture for 16 weeks in drinking water and the other no (Nef). A control group (C) included sham-nephrectomized rats. Serum creatinine and IS concentrations were measured using high-performance liquid chromatography with diode array detector (HPLC-DAD). Optical microscopy and two-photon excitation microscopy was used to study kidney and heart samples. The Lac group, which received the synbiotic, reduced IS by 0.8% while the Nef group increased it by 38.8%. Histological analysis of kidneys showed that the Lac group increased fibrotic areas by 12% and the Nef group did it by 25%. The synbiotic did not reduce cardiac fibrosis. Therefore, the putative synbiotic showed that function reducing IS and the progression of CKD in a rat model, but no heart protection was observed.

Keywords: CKD; CVD; indoxyl sulfate; renal fibrosis; synbiotic.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Serum creatinine levels of Sprague-Dawley rats at the beginning and at the end of the 16 weeks administration of the synbiotic. (b) Differences of the means for final creatinine concentrations with 95% Tukey simultaneous confidence intervals (If an interval does not contain zero, the corresponding means are significantly different). Nef: nephrectomized rats not receiving the synbiotic, Lac: nephrectomized rats receiving the synbiotic, Control: sham-nephrectomized rats.
Figure 2
Figure 2
(a) Serum indoxyl sulfate (IS) levels of Sprague-Dawley rats at the beginning and at the end of the 16 weeks administration of the synbiotic. (b) Differences of the means for final IS concentrations with 95% Tukey simultaneous confidence intervals (If an interval does not contain zero, the corresponding means are significantly different). Nef: nephrectomized rats not receiving the synbiotic, Lac: nephrectomized rats receiving the synbiotic, Control: sham-nephrectomized rats.
Figure 3
Figure 3
Hematocrit values of Sprague-Dawley rats at the end of the 16 weeks administration of the synbiotic. Nef: nephrectomized rats not receiving the synbiotic, Lac: nephrectomized rats receiving the synbiotic, Control: sham-nephrectomized rats.
Figure 4
Figure 4
Histological sections of kidneys of Sprague-Dawley rats. (A–C): Masson’s trichrome stain of nephrons. Fibrotic areas are observed in blue (arrows). (D–F): same tissue observed by two-photon excitation microscopy. Fibrotic tissue is observed in green. Nef: nephrectomized rats not receiving the synbiotic, Lac: nephrectomized rats receiving the synbiotic, Control: sham-nephrectomized rats. Scale bar: 100 µm for (A–C) micrographs and 50 µm for (D–F) micrographs.
Figure 5
Figure 5
Masson’s trichrome (MT) staining of the heart of Sprague-Dawley rats. Fibrotic areas are stained in blue (arrows). Nef: nephrectomized rats not receiving the synbiotic, Lac: nephrectomized rats receiving the synbiotic. Control: sham-nephrectomized rats. Scale bar 100 µm.
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