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: Rats that had undergone I/R exhibited a massive increase in tissue markers of oxidative stress, such as TBARS production, an index of peroxidation of cell membrane lipids, and 8-OHdG, a marker of free radical-induced DNA damage (Fig. 3A and B, respectively). The robust increase in TBARS and 8-OHdG levels was blunted by rhRLX administration. Renal I/R injury evoked a significant decrease in the activity of the endogenous antioxidant enzymes MnSOD and CuZnSOD (Fig. 4A and B, respectively), which was associated with a slight suppression of their protein expression (Fig. 4C and D). Interestingly, rhRLX administration almost completely abolished the I/R-induced reduction in MnSOD and CuZnSOD activities and evoked a massive protein up-regulation, above the control levels. On the other hand, rhRLX administration to sham-operated animals had no significant effect on any of the measured markers.
Affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.