title: Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP: role of AMPK/PPARα/UCP2 axis.
abstract: OBJECTIVE
  Renal damage precedes occurrence of stroke in high-sodium/low-potassium-fed stroke-prone spontaneously hypertensive rat (SHRSP). We previously reported a marked suppression of uncoupling protein-2 (UCP2) upon high-salt Japanese-style diet in SHRSP kidneys. Vegetable compounds are known to exert protective effects in cardiovascular diseases. We aimed at evaluating the impact of Brassica oleracea sprouts juice toward renal damage in Japanese diet-fed SHRSP and exploring the role of 5'-adenosine monophosphate-activated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α)/peroxisome proliferator-activated receptor-α (PPARα)/UCP2 axis.
  
  
  METHODS
  SHRSP received Japanese diet for 4 weeks. A group of SHRSP received Japanese diet and B. oleracea. A third group received Japanese diet, B. oleracea, and PPARα inhibitor (GW6471). A group of SHRSP fed with regular diet served as control.
  
  
  RESULTS
  Japanese diet induced marked increases of oxidative stress, inflammation, and proteinuria, along with glomerular and tubular damage, as compared with regular diet. A significant suppression of AMPK/UCP2 pathway was observed. Despite Japanese diet feeding, concomitant administration of B. oleracea prevented oxidative stress accumulation, inflammation, renal damage, and proteinuria. All components of the UCP2 regulatory pathway were significantly increased by B. oleracea. Superoxide dismutase 2 and phosphoendothelial nitric oxide synthase were also stimulated. Addition of PPARα inhibitor to B. oleracea and Japanese diet significantly reduced the B. oleracea beneficial effects. SBP levels were comparable among the different groups of rats.In vitro, UCP2 inhibition by genipin offset the antioxidant effect of B. oleracea in renal mesangial and proximal tubular cells.
  
  
  CONCLUSIONS
  B. oleracea administration prevented renal damage in salt-loaded SHRSP, independently from SBP, with parallel stimulation of AMPK/SIRT1/PGC1α/PPARα/UCP2 axis. Stimulation of the latter mechanism may provide relevant renal protective effect and play a therapeutic role in target organ damage progression in hypertension.
authors: aIRCCS Neuromed, Pozzilli (Isernia) bDepartment of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea cDepartment of Biology and Biotechnology, Sapienza University dFood and Nutrition Research Center (CRA-NUT), Consiglio per la Ricerca e la Sperimentazione in Agricoltura, Rome eCentro Cardiologico Monzino, IRCCS fDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan gDepartment of Experimental Medicine, Medical Physiopathology, Food Science and Endocrinology Section, Sapienza University, Rome, Italy.
authors: Speranza
authors: S
authors: Rubattu
authors: Sara
authors: S
authors: Di Castro
authors: Maria
authors: M
authors: Cotugno
authors: Franca
authors: F
authors: Bianchi
authors: Roberto
authors: R
authors: Mattioli
authors: Simona
authors: S
authors: Baima
authors: Rosita
authors: R
authors: Stanzione
authors: Michele
authors: M
authors: Madonna
authors: Cristina
authors: C
authors: Bozzao
authors: Simona
authors: S
authors: Marchitti
authors: Paolo
authors: P
authors: Gelosa
authors: Luigi
authors: L
authors: Sironi
authors: Alice
authors: A
authors: Pignieri
authors: Mariateresa
authors: M
authors: Maldini
authors: Anna Maria
authors: AM
authors: Giusti
authors: Mirella
authors: M
authors: Nardini
authors: Giorgio
authors: G
authors: Morelli
authors: Paolo
authors: P
authors: Costantino
authors: Massimo
authors: M
authors: Volpe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001937:Brassica / Q000737:chemistry*; D004032:Diet / Q000009:adverse effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications; D007473:Ion Channels / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology; D007674:Kidney Diseases / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage*; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011918:Rats, Inbred SHR; D036226:Seedlings / Q000737:chemistry; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology; D000071246:Uncoupling Protein 2
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D039823:Iridoids; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D010936:Plant Extracts; D017673:Sodium Chloride, Dietary; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C007834:genipin; D055372:AMP-Activated Protein Kinases