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Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury.

Collino M, Rogazzo M, Pini A, Benetti E, Rosa AC, Chiazza F, Fantozzi R, Bani D, Masini E - J. Cell. Mol. Med. (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.

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Effects of I/R and rhRLX on activity and expression of manganese-superoxide dismutases (MnSOD) and copper-zinc-superoxide dismutases (CuZnSOD) in kidney samples. Activity (A and B) and protein expression (C and D) of the SOD isoforms mitochondrial MnSOD and cytosolic CuZnSOD were measured in kidney homogenates of sham-operated rats (Sham) and rats that underwent 1-hr ischaemia and 6-hr reperfusion (IR) in the absence or presence of rhRLX (5 μg/kg, i.v.; Sham+RLX and IR+RLX). Each immunoblot is from a single experiment and is representative of three separate experiments. Densitometric analysis of the bands is expressed as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized using the related sham-operated band. Data are means ± SEM of three separate experiments for Western Blot and five animals/group for SOD activity. ⋆P < 0.05 versusIR.
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fig04: Effects of I/R and rhRLX on activity and expression of manganese-superoxide dismutases (MnSOD) and copper-zinc-superoxide dismutases (CuZnSOD) in kidney samples. Activity (A and B) and protein expression (C and D) of the SOD isoforms mitochondrial MnSOD and cytosolic CuZnSOD were measured in kidney homogenates of sham-operated rats (Sham) and rats that underwent 1-hr ischaemia and 6-hr reperfusion (IR) in the absence or presence of rhRLX (5 μg/kg, i.v.; Sham+RLX and IR+RLX). Each immunoblot is from a single experiment and is representative of three separate experiments. Densitometric analysis of the bands is expressed as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized using the related sham-operated band. Data are means ± SEM of three separate experiments for Western Blot and five animals/group for SOD activity. ⋆P < 0.05 versusIR.

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.


Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury.

Collino M, Rogazzo M, Pini A, Benetti E, Rosa AC, Chiazza F, Fantozzi R, Bani D, Masini E - J. Cell. Mol. Med. (2013)

Effects of I/R and rhRLX on activity and expression of manganese-superoxide dismutases (MnSOD) and copper-zinc-superoxide dismutases (CuZnSOD) in kidney samples. Activity (A and B) and protein expression (C and D) of the SOD isoforms mitochondrial MnSOD and cytosolic CuZnSOD were measured in kidney homogenates of sham-operated rats (Sham) and rats that underwent 1-hr ischaemia and 6-hr reperfusion (IR) in the absence or presence of rhRLX (5 μg/kg, i.v.; Sham+RLX and IR+RLX). Each immunoblot is from a single experiment and is representative of three separate experiments. Densitometric analysis of the bands is expressed as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized using the related sham-operated band. Data are means ± SEM of three separate experiments for Western Blot and five animals/group for SOD activity. ⋆P < 0.05 versusIR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117562&req=5

fig04: Effects of I/R and rhRLX on activity and expression of manganese-superoxide dismutases (MnSOD) and copper-zinc-superoxide dismutases (CuZnSOD) in kidney samples. Activity (A and B) and protein expression (C and D) of the SOD isoforms mitochondrial MnSOD and cytosolic CuZnSOD were measured in kidney homogenates of sham-operated rats (Sham) and rats that underwent 1-hr ischaemia and 6-hr reperfusion (IR) in the absence or presence of rhRLX (5 μg/kg, i.v.; Sham+RLX and IR+RLX). Each immunoblot is from a single experiment and is representative of three separate experiments. Densitometric analysis of the bands is expressed as relative optical density (O.D.), corrected for the corresponding β-actin contents and normalized using the related sham-operated band. Data are means ± SEM of three separate experiments for Western Blot and five animals/group for SOD activity. ⋆P < 0.05 versusIR.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.

Show MeSH
Related in: MedlinePlus