title: Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the renal function recovery after suspension of GENTA treatment in rats.
abstract: GENTA nephrotoxicity is likely to be caused, among other factors, by an increase of vasoconstrictors or a decrease of vasodilators such as NO. Few days after discontinuing GENTA treatment, the renal function is recovered, but if risk factors like advanced age, previous renal dysfunction, simultaneous use of other nephrotoxic drugs or dehydration are present, severe and progressive renal disease occurs. The aim of this study was to evaluate the renal function in rats during GENTA treatment and after its suspension as well as its relationship with NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW) intraperitonially during 10 days; both n=24. Twelve animals of each group were sacrificed after blood and 24 h urine were collected, and their kidneys were removed for histology. In another rats this procedure underwent after 20 or 30 days of GENTA suspension. GENTA treated group developed a marked decrease in renal function, characterized by an increased serum urea and decreased creatinine clearance; NO was increased in the serum and decreased in the urine; all P < 0.01 vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA suspension we observed a normalization of urea, creatinine clearance and serum and urinary NO; the histological lesions were also attenuated. We suggest that NO could play a role in GENTA induced nephrotoxicity and recovery. The understanding of this physiopathology could be an useful tool to prevent or blunt the nephrotoxicity progression, mainly when risk factors are present.
authors.affiliation: Nephrology Division, Universidade Federal de São Paulo--Escola Paulista de Medicina, São Paulo, Brazil.
authors.forename: Joelma Santina
authors.initials: JS
authors.lastname: Christo
authors.forename: Adelson Marçal
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: Margaret Gori
authors.initials: MG
authors.lastname: Mouro
authors.forename: Marcos Antonio
authors.initials: MA
authors.lastname: Cenedeze
authors.forename: Manuel de Jesus
authors.initials: Mde J
authors.lastname: Simões
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.forename: Elisa Mieko Suemitsu
authors.initials: EM
authors.lastname: Higa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced; D007677:Kidney Function Tests; D008297:Male; D009569:Nitric Oxide; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009569:Nitric Oxide