Limits...
Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models.

Cui J, Bai XY, Sun X, Cai G, Hong Q, Ding R, Chen X - Sci Rep (2015)

Bottom Line: At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group.In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated.After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

ABSTRACT
Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy.

No MeSH data available.


Related in: MedlinePlus

Effect of rapamycin on autophagy in gentamicin-treated AKI minipigs.(a) The levels of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1 in kidney extracts of animals treated with various doses of gentamicin were quantified by Western blotting. CON: the control group, GEN: the gentamicin-treated group, Rapa: the gentamicin and rapamycin treated group. The gels have been run under the same experimental conditions. (b–k) Quantitative measurements of band densities of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1. Protein expression data are presented as means ± SDs (n = 6). *p < 0.05 vs. GEN.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4459224&req=5

f8: Effect of rapamycin on autophagy in gentamicin-treated AKI minipigs.(a) The levels of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1 in kidney extracts of animals treated with various doses of gentamicin were quantified by Western blotting. CON: the control group, GEN: the gentamicin-treated group, Rapa: the gentamicin and rapamycin treated group. The gels have been run under the same experimental conditions. (b–k) Quantitative measurements of band densities of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1. Protein expression data are presented as means ± SDs (n = 6). *p < 0.05 vs. GEN.

Mentions: The levels of LC3-I, LC3-II, p62, Poly UB, PINK1, p-Parkin, and AMBRA1 were significantly lower in the kidneys of rapamycin- than gentamicin-treated animals. The Parkin levels were, however, similar. Bnip3 and HIF-1α levels in the kidneys of rapamycin were higher than gentamicin-treated animals (Fig. 8).


Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models.

Cui J, Bai XY, Sun X, Cai G, Hong Q, Ding R, Chen X - Sci Rep (2015)

Effect of rapamycin on autophagy in gentamicin-treated AKI minipigs.(a) The levels of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1 in kidney extracts of animals treated with various doses of gentamicin were quantified by Western blotting. CON: the control group, GEN: the gentamicin-treated group, Rapa: the gentamicin and rapamycin treated group. The gels have been run under the same experimental conditions. (b–k) Quantitative measurements of band densities of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1. Protein expression data are presented as means ± SDs (n = 6). *p < 0.05 vs. GEN.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4459224&req=5

f8: Effect of rapamycin on autophagy in gentamicin-treated AKI minipigs.(a) The levels of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1 in kidney extracts of animals treated with various doses of gentamicin were quantified by Western blotting. CON: the control group, GEN: the gentamicin-treated group, Rapa: the gentamicin and rapamycin treated group. The gels have been run under the same experimental conditions. (b–k) Quantitative measurements of band densities of LC3, p62/SQSTM1, poly UB, Bnip3, HIF-1α, PINK1, Parkin, p-Parkin and AMBRA1. Protein expression data are presented as means ± SDs (n = 6). *p < 0.05 vs. GEN.
Mentions: The levels of LC3-I, LC3-II, p62, Poly UB, PINK1, p-Parkin, and AMBRA1 were significantly lower in the kidneys of rapamycin- than gentamicin-treated animals. The Parkin levels were, however, similar. Bnip3 and HIF-1α levels in the kidneys of rapamycin were higher than gentamicin-treated animals (Fig. 8).

Bottom Line: At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group.In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated.After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

ABSTRACT
Gentamicin may cause acute kidney injury. The pathogenesis of gentamicin nephrotoxicity is unclear. Autophagy is a highly conserved physiological process involved in removing damaged or aged biological macromolecules and organelles from the cytoplasm. The role of autophagy in the pathogenesis of gentamicin nephrotoxicity is unclear. The miniature pigs are more similar to humans than are those of rodents, and thus they are more suitable as human disease models. Here we established the first gentamicin nephrotoxicity model in miniature pigs, investigated the role of autophagy in gentamicin-induced acute kidney injury, and determined the prevention potential of rapamycin against gentamicin-induced oxidative stress and renal dysfunction. At 0, 1, 3, 5, 7 and 10 days after gentamicin administration, changes in autophagy, oxidative damage, apoptosis and inflammation were assessed in the model group. Compared to the 0-day group, gentamicin administration caused marked nephrotoxicity in the 10-day group. In the kidneys of the 10-day group, the level of autophagy decreased, and oxidative damage and apoptosis were aggravated. After rapamycin intervention, autophagy activity was activated, renal damage in proximal tubules was markedly alleviated, and interstitium infiltration of inflammatory cells was decreased. These results suggest that rapamycin may ameliorate gentamicin-induced nephrotoxicity by enhancing autophagy.

No MeSH data available.


Related in: MedlinePlus