Association of apolipoprotein B/apolipoprotein A1 ratio and cardiovascular events in rheumatoid arthritis: results of the CARMA study.
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Zegarra-Mondragón Sixto, López-González Ruth, Martín-Martínez María Auxiliadora, García-Gómez Carmen, Sánchez-Alonso Fernando, González-Juanatey Carlos, Manrique Arija Sara, Bonilla Hernán Gema, Martínez Pardo Silvia, Ruibal Escribano Ana, Pagán García Encarnación, Delgado Frías Esmeralda, Rivera Redondo Javier, Delgado Sánchez Mónica, Rodriguez Cambrón Ana Belén, Moreno Ramos Manuel José, Rodríguez Montero Sergio Antonio, Navío Marco Maria Teresa, Morcillo Valle Mercedes, García González Javier, Bachiller Corral Javier, Llorca Javier, Castañeda Santos, González-Gay Miguel Ángel, CARMA Project Collaborative Group
Аннотация
METHODS: 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed.
RESULTS: The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed.
CONCLUSION: This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.