title: Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney.
abstract: The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin (Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum-mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.
authors.affiliation: Division of Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, 25123, Brescia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corsetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Antona
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruocco
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchiotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Romano
authors.forename: Laura
authors.initials: L
authors.lastname: Tedesco
authors.forename: Francesco
authors.initials: F
authors.lastname: Dioguardi
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Enzo
authors.initials: E
authors.lastname: Nisoli
mesh_terms: D000601:Amino Acids, Essential / Q000494:pharmacology*; D000818:Animals; D019587:Dietary Supplements; D000091342:Endoplasmic Reticulum Chaperone BiP; D005464:Fluorobenzenes / Q000009:adverse effects / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000601:Amino Acids, Essential; D000091342:Endoplasmic Reticulum Chaperone BiP; D005464:Fluorobenzenes; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D024101:Mitochondrial Proteins; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium