Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy

Experimental swelling protocol induced by Ca²⁺.

<p>Liraglutide and sitagliptin subgroups showed increased mitochondrial permeability transition pore resistance in brain (a) and heart (b) tissues. Analyses were made in rats having received liraglutide and sitagliptin for 4 weeks after high fat diet during 18 weeks. Data are shown as mean ± SEM; <i>n</i> = 5.</p

Effects of high fat diet and incretin-based-therapies on autonomic nervous system.

<p><b>(a)</b> Effects of high fat diet alone or in combination with liraglitude or sitagliptin treatments on R-R intervals and time-domain parasympathetic indexes of heart rate variability (SDNN, pNN5% and RMSSD). (<b>b</b>) Effects of high fat diet alone or in combination with liraglitude or sitagliptin treatments on frequency-domain of heart rate variability (SDNN, pNN5% and RMSSD). High-frequency (HF), low- frequency (LF) power spectra and the ratio between low-frequency to high-frequency (LF HF^-1 ratio) power spectra are shown. The following groups (n = 5 each) were examined: Control (CTRL), high fat diet (HFD), high fat diet plus liraglutide (HFD Liraglutide) and high fat diet plus sitagliptin (HFD Sitagliptin). Data are shown as mean ± SEM; <i>n</i> = 5–8. *<i>p<</i>0.05 vs. CTRL; **<i>p<</i>0.01 vs. CTRL; ^†<i>p<</i>0.05 vs. HFD; ^†††<i>p<</i>0.001 vs. HFD; ^‡<i>p<</i> 0.05 vs. HFD Liraglutide; ^‡‡<i>p<</i>0.01 vs. HFD Liraglutide and ^‡‡‡<i>p<</i>0.001 vs. HFD Liraglutide.</p

Dataset for: Diabetic rats present higher urinary loss of proteins and lower renal expression of megalin, cubilin, ClC-5 and CFTR

Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator) and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine by calculating clearance and fractional excretion of solutes. The RNA and protein content of ClC-5, CFTR, megalin and cubilin was determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin and transferrin in the DM group than in the CTRL group. Furthermore, the renal cortex and proximal tubule of diabetic animals showed downregulation of megalin, cubilin, ClC-5 and CFTR, critical components of the endocytic apparatus. These data suggest dysfunction in proximal tubule low-molecular-weight endocytosis and protein glomerulus filtration in the kidney of diabetic rats