Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Methods
2.2. Urine Sample Collection
2.3. Hemodynamic Measurements in the Days of Tissue Collections
2.4. Measurement of Various Plasma Pathogenic Factors
2.5. Isolated Renal Perfusion Study
2.6. Tissue Profiles
2.7. Flow Cytometry
2.8. Materials
2.9. Statistical Analysis
3. Results
3.1. Cirrhotic BDL Rats Are Characterized by Progressive Renal Dysfunction that Can Be Attenuated by Chronic Pioglitazone Treatment
3.2. Chronic Pioglitazone Treatment Suppressed Serum Endotoxin, TNFα, IL-6, ALT and Total Bilirubin in Advanced Cirrhotic Rats
3.3. Acute LPS Administration Downregulated Renal PPARγ Expression and Increased Renal M1 Macrophage Infiltration and Inflammation in Cirrhotic Ascitic Rats
3.4. Effects of Chronic Pioglitazone Pre-Treatment Suppressed LPS-Induced TNFα -Mediated Renal Injury and Fibrosis in Cirrhotic Ascitic Rats
3.5. Chronic PPARγ Agonist Pioglitazone Pre-Treatment Attenuates the LPS-Induced TNFα-Mediated Increase in Renal Vascular Resistance (RVR) in Cirrhotic Ascitic Rats
3.6. Chronic Pioglitazone Pre-Treatment Attenuated LPS-Induced TNFα/NFκB-Mediated Renal Tissue and Renal Vascular Inflammation in BDL Rats
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Name | Forwards | Reverse |
---|---|---|
TNFα | 5′-GCT CAC AAT GTC TGT GCT TAGAG-3′ | 5′-GCA GTA GCC ACA GCT CCAG-3′ |
MCP-1 | 5′-ATG CAG TTA ATG CCC CAC TC-3′ | 5′-TGC TGC TGG TGA TTG TCT TG-3′ |
IL-4 | 5′-GGA TGT GCC AAA CGT CCT C-3′ | 5′-GAG TTC TTC TTC AAG CAT GGAG-3′ |
IL-13 | 5′-CTT TCT TTA GCG GCC AC-3 | 5′-CAG AGC GCC ATG AAG CCC AGAG-3′ |
18S | 5′-ACGGAAGGGCACCACCAGGA-3′ | 5′-CACCACCACCCACGGAATCG-3 |
Sham (n = 4) | Sham+LPS (n = 4) | Sham-Pio+LPS (n = 4) | BDL (n = 9) | BDL+LPS (n = 9) | BDL-Pio+LPS (n = 9) | |
---|---|---|---|---|---|---|
MAP (mmHg) | 110 ± 14 | 106 ± 9 | 109 ± 11 | 92 ± 12 * | 87 ± 5 # | 90 ± 6 |
Cardiac output (CO, mL/min) | 229 ± 38 | 203 ± 28 | 211 ± 19 | 259 ± 41 * | 212 ± 29 # | 242 ± 33 |
PVP (mmHg) | 7.8 ± 0.9 | 9.1 ± 0.6 | 8.2 ± 0.8 | 17.3 ± 1.6 * | 18.2 ± 2.3 | 17.9 ± 2.1 |
RABF (mL/min·100 g) | 5.1 ± 1.4 | 5.6 ± 1.6 | 5.4 ± 1.2 | 3.0 ± 1.3 * | 3.8 ± 0.5 | 3.6 ± 0.9 |
Body weight (BW, gram) | 354.6 ± 18.4 | 349.8 ± 16.5 | 347.2 ± 13.9 | 306.4 ± 21.4 * | 309.3 ± 18.9 | 310.2 ± 14.3 |
Kidney weight (KW, both sides, grams) | 1.25 ± 0.007 | 1.22 ± 14.8 | 1.21 ± 0.018 | 1.9 ± 0.078 | 2.1 ± 0.065 | 1.4 ± 0.009 |
KW/BW (10−3) | 0.36 ± 0.0021 | 0.35 ± 0.003 | 0.35 ± 0.007 | 0.62 ± 0.004 * | 0.68 ± 0.003 | 0.45 ± 0.002 # |
Renal hydroxyproline (µg/mg kidney) | 312 ± 22 | 309 ± 27 | 310 ± 19 | 429 ± 12 * | 418 ± 17 | 420 ± 8 |
Sham (n = 4) | Sham+LPS (n = 4) (Mean % Increase from Data of Sham Group) | Sham-Pio+LPS (n = 4) (Mean % Increase from Data of Sham Group) | BDL (n = 9) | BDL+LPS (n = 9) (Mean % Increase from Data of Sham Group) | BDL-Pio+LPS (n = 9) (Mean % Increase from Data of Sham Group) | |
---|---|---|---|---|---|---|
(Endotoxin) (pg/mL) | 7.3 ± 0.9 | 9.6 ± 0.8 | 8.3 ± 0.5 | 17.9 ± 2.6 * | 27.3 ± 2.8 ## | 19.4 ± 1.8 ‡ |
(TNFα) (pg/mL) | 12.9 ± 5.4 | 34.8 ± 4.8 | 17.1 ± 2.8 | 56.9 ± 8.1 * | 168.3 ± 9.6 ## | 64.1 ± 7.1 ‡ |
(IL-6) (pg/mL) | 10.5 ± 1.1 | 17.6 ± 2.1 | 14.2 ± 1.6 | 29.8 ± 3.4 * | 73.6 ± 1.9 ## | 31.8 ± 2.2 ‡‡ |
Fasting blood sugar (mg/dL) | 95 ± 15 | 108 ± 20 | 98 ± 16 | 112 ± 23 | 123 ± 19 | 119 ± 16 |
(Albumin) (g/L) | 4.1 ± 0.7 | 3.7 ± 0.9 | 3.9 ± 0.8 | 2.9 ± 0.9 | 2.6 ± 0.4 | 2.8 ± 0.7 |
(ALT) (IU/L) | 58 ± 14 | 69 ± 13 | 61 ± 12 | 98 ± 7 * | 352 ± 15 ## | 168 ± 12 ‡‡ |
(Total bilirubin) (mg/dL) | 0.38 ± 0.09 | 0.58 ± 0.04 | 0.41 ± 0.06 | 7.8 ± 0.8 * | 18.5 ± 1.7 ## | 13.1 ± 2.5 ‡ |
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Liu, S.-Y.; Huang, C.-C.; Huang, S.-F.; Liao, T.-L.; Kuo, N.-R.; Yang, Y.-Y.; Li, T.-H.; Liu, C.-W.; Hou, M.-C.; Lin, H.-C. Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats. Cells 2021, 10, 3044. https://doi.org/10.3390/cells10113044
Liu S-Y, Huang C-C, Huang S-F, Liao T-L, Kuo N-R, Yang Y-Y, Li T-H, Liu C-W, Hou M-C, Lin H-C. Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats. Cells. 2021; 10(11):3044. https://doi.org/10.3390/cells10113044
Chicago/Turabian StyleLiu, Szu-Yu, Chia-Chang Huang, Shiang-Fen Huang, Tsai-Ling Liao, Nai-Rong Kuo, Ying-Ying Yang, Tzu-Hao Li, Chih-Wei Liu, Ming-Chih Hou, and Han-Chieh Lin. 2021. "Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats" Cells 10, no. 11: 3044. https://doi.org/10.3390/cells10113044