Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice.
Acute kidney injury (AKI) represents a complex clinical condition associated with significant morbidity and mortality. Approximately, 19-33% AKI episodes in hospitalized patients are related to drug-induced nephrotoxicity. Although, considered safe, non-steroidal anti-inflammatory drugs such as diclofenac have received special attention in the past years due to the potential risk of renal damage. Vinpocetine is a nootropic drug known to have anti-inflammatory properties. In this study, we investigated the effect and mechanisms of vinpocetine in a model of diclofenac-induced AKI. We observed that diclofenac increased proteinuria and blood urea, creatinine, and oxidative stress levels 24h after its administration. In renal tissue, diclofenac also increased oxidative stress and induced morphological changes consistent with renal damage. Moreover, diclofenac induced kidney cells apoptosis, up-regulated proinflammatory cytokines, and induced the activation of NF-κB in renal tissue. On the other hand, vinpocetine reduced diclofenac-induced blood urea and creatinine. In the kidneys, vinpocetine inhibited diclofenac-induced oxidative stress, morphological changes, apoptosis, cytokine production, and NF-κB activation. To our knowledge, this is the first study demonstrating that diclofenac-induced AKI increases NF-κB activation, and that vinpocetine reduces the nephrotoxic effects of diclofenac. Therefore, vinpocetine is a promising molecule for the treatment of diclofenac-induced AKI.
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil.
Victor
V
Fattori
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil.
Sergio M
SM
Borghi
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil.
Carla F S
CFS
Guazelli
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil.
Andressa C
AC
Giroldo
Departamento de Medicina, Divisão de Endocrinologia, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350 Londrina, Paraná, Brazil.
Jefferson
J
Crespigio
Laboratório de Anatomia Patológica, Centro de Ciências de Saúde, Universidade Estadual de Londrina, 86038-350 Londrina, Paraná, Brazil.
Allan J C
AJC
Bussmann
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil.
Letícia
L
Coelho-Silva
Departamento de Medicina, Divisão de Endocrinologia, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350 Londrina, Paraná, Brazil.
Natasha G
NG
Ludwig
Departamento de Medicina, Divisão de Endocrinologia, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350 Londrina, Paraná, Brazil.
Tânia L
TL
Mazzuco
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, 86038-350 Londrina, Paraná, Brazil.
Rubia
R
Casagrande
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, Paraná, Brazil. Electronic address: waverri@uel.br.
Waldiceu A
WA
Verri
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004008:Diclofenac / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D018697:Nootropic Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D014748:Vinca Alkaloids / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D018697:Nootropic Agents; D020011:Protective Agents; D014748:Vinca Alkaloids; D004008:Diclofenac; C013983:vinpocetine
Acute kidney injury; Diclofenac; NF-κB; Proteinuria; Reactive oxygen species; Vinpocetine