Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury.
Bottom Line: Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N-acetyl-β-glucosaminidase) evoked by renal I/R.These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical-induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes Mn- and CuZn-superoxide dismutases (SOD).Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX-induced activation of endothelial nitric oxide synthase and up-regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal-regulated protein kinase (ERK) 1/2, respectively.
Affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.Show MeSH
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Mentions: Figure 2 depicts representative histopathological features of the kidney (cortex and medulla) from rats belonging to the different experimental groups. When compared with the normal kidney morphology of the sham-operated rats, the samples taken from the animals undergoing renal I/R showed typical features of glomerular, tubular and vascular injury. In particular, large tissue areas in both the renal cortex and medulla showed widespread tubular cell vacuolization with reduced or absent ruffled border, accompanied by focal necrosis, shedding of the tubular epithelial lining and formation of hyaline tubular casts. The interstitial connective tissue showed very dilated microvessels filled with blood (peliosis) and sparse haemorrhage foci. Glomeruli in the renal cortex also showed cell microvacuolation and occasional blood extravasation in the Bowman capsule. Of note, rhRLX administration at reperfusion markedly reduced these renal abnormalities, the most evident changes being tubular cell microvacuolation and a moderate degree of microvascular dilation. Semi-quantitative scoring of kidney injury performed on the histological slides confirmed the visual observations and showed that rhRLX significantly attenuates renal cell damage (Fig. 2).
Affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.