title: Differential efficiency of simvastatin and lipoic acid treatments on Bothrops jararaca envenomation-induced acute kidney injury in mice.
abstract: Snake bite accidents by Bothrops genus is an important public health issue in Brazil and one of its most serious complications is the acute kidney injury (AKI). Here we evaluated the effects of Bothrops jararaca venom (vBj) and the treatments with lipoic acid (LA) and simvastatin (SA) on renal function, aminopeptidase (AP) activities and renal redox status. Primordial events for establishment of AKI by vBj were hyperuricemia, hypercreatinemia, urinary hyperosmolality, renal oxidative stress and reduction of hematocrit and protein content in the membrane of renal cortex and medulla and in the plasma. In the renal cortex and medulla the changes caused by vBj in soluble and membrane-bound AP activities had a similar pattern. The beneficial effects of LA and SA on envenomed mice were similar on the hyperuricemia, renal oxidative stress and reduction of hematocrit. LA mitigated the hypercreatinemia, but exacerbated the urinary urea and creatinine, whereas SA mitigated the decrease of plasma urea, urinary hyperosmolality and hypercreatinuria induced by vBj. The beneficial effects of LA and especially of SA on renal effects of vBj open a new perspective for clinical investigations of these drugs as coadjuvant agents in the serotherapy of Bothrops envenomation.
authors.affiliation: Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Juliana Marton
authors.initials: JM
authors.lastname: Barone
authors.forename: Rafaela Fadoni
authors.initials: RF
authors.lastname: Alponti
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Frezzatti
authors.forename: Leonardo
authors.initials: L
authors.lastname: Zambotti-Villela
authors.forename: Paulo Flávio
authors.initials: PF
authors.lastname: Silveira
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017837:Bothrops / Q000502:physiology*; D003435:Crotalid Venoms / Q000633:toxicity*; D004195:Disease Models, Animal; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D012909:Snake Bites / Q000188:drug therapy / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D003435:Crotalid Venoms; D008063:Thioctic Acid; D019821:Simvastatin; D000626:Aminopeptidases