[HTML][HTML] Rapamycin protects against gentamicin-induced acute kidney injury via autophagy in mini-pig models

J Cui, XY Bai, X Sun, G Cai, Q Hong, R Ding, X Chen - Scientific reports, 2015 - nature.com
J Cui, XY Bai, X Sun, G Cai, Q Hong, R Ding, X Chen
Scientific reports, 2015nature.com
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 …
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.
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