Preconditioning induced by gentamicin protects against acute kidney injury: The role of prostaglandins but not nitric oxide

Journal Article · Sun May 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.02.022· OSTI ID:21535300

Pessoa, Edson A; Convento, Marcia B; Ribas, Otoniel S; Tristao, Vivian R; Reis, Luciana Aparecida; Borges, Fernanda T; Schor, Nestor

Nephrotoxicity is the main side effect of gentamicin (GENTA). Preconditioning (PC) refers to a situation in which an organ subjected to an injury responds less intensely when exposed to another injury. The aim of this study was to evaluate the effect of PC with GENTA on nephrotoxic acute kidney injury (AKI). GENTA group rats were injected daily with GENTA (40 mg/kg/BW) for 10 days. PC animals were injected with GENTA for 3 days (40 mg/kg/BW/daily) and, after one rest week, were injected daily with GENTA for 10 days. Animals of the L-NAME and DICLO groups were preconditioned for 3 days and then received daily injections of GENTA for 10 days; they were concomitantly treated with L-NAME (10 mg/kg/BW) and diclofenac (DICLO, 5 mg/kg/BW) for 13 days. Blood and urine were collected for measurement of serum creatinine, urea, urine sodium, protein, hydroperoxides, lipid peroxidation and nitric oxide (NO). The animals were killed; kidneys were removed for histology and immunohistochemistry for apoptosis and cell proliferation. GENTA group rats showed an increase in plasma creatinine, urea, urine sodium, hydroperoxides, lipid peroxidation, proteinuria, necrosis and apoptosis, characterizing nephrotoxic AKI. PC animals showed a decrease in these parameters and increased proliferation. The blockade of NO synthesis by L-NAME potentiated the protective effect, suggesting that NO contributed to the injury caused by GENTA. The blockade of prostaglandin synthesis with DICLO increased serum and urinary parameters, blunting the protective effect of PC. Our data suggest that PC could be a useful tool to protect against nephrotoxic AKI.

• OSTI ID: 21535300
• Journal Information: Toxicology and Applied Pharmacology, Vol. 253, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.02.022; PII: S0041-008X(11)00076-7; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BLOOD
CELL PROLIFERATION
CREATININE
HISTOLOGY
INJURIES
KIDNEYS
LIPIDS
NECROSIS
NITRIC OXIDE
PROSTAGLANDINS
RATS
SIDE EFFECTS
SODIUM
SYNTHESIS
UREA
URINE
ALKALI METALS
AMIDES
ANIMALS
AZOLES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARBONIC ACID DERIVATIVES
CHALCOGENIDES
DISEASES
ELEMENTS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IMINES
MAMMALS
MATERIALS
METALS
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PATHOLOGICAL CHANGES
RODENTS
VERTEBRATES
WASTES