Naslov
Aucubin administered by either oral or parenteral route protects against cisplatin-induced acute kidney injury in mice

Autori
Potočnjak, Iva ; Marinić, Jelena ; Batičić, Lara ; Šimić, Lidija ; Broznić, Dalibor ; Domitrović, Robert

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Archives of Industrial Hygiene and Toxicology 2021, 72(1), Abstracts of the 6th Croatian Congress of Toxicology with International Participation CROTOX 2021 / Herman, Makso ; Kopljar, Nevenka ; Brčić Karačonji, Irena ; Lyons, Daniel Mark - , 2021, 43-43

Skup
6th Croatian congress of toxicology with international participation (CROTOX 2021)

Mjesto i datum
Rabac, Hrvatska, 03.10.2021. - 06.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
apoptosis ; inflammation ; oxidative stress ; protective effect ; western blot analysis

Sažetak
Aucubin, an iridoid glucoside isolated from the leaves of Aucuba japonica and other herbs is a pharmacologically active natural compound that possesses anti-inflammatory, antioxidative, and other beneficial properties. This study aimed to evaluate the protective effect of aucubin against cisplatin (CP)-induced acute kidney injury in mice and the mechanism of its action. Aucubin was administrated to mice orally or intraperitoneally (i.p.) (1.5 and 5 mg/kg) for two consecutive days, two days after i.p. injection of cisplatin (11 mg/kg). Treatment with aucubin by both routes of administration ameliorated histopathological changes and reduced elevated serum markers of kidney injury (blood urea nitrogen and creatinine). CP administration increased renal expression of heme oxygenase-1 (HO-1) and 4- hydroxynonenal (4-HNE), as well as tumour necrosis factor-alpha (TNF-α), determined by western blot analysis, which was dose-dependently ameliorated by aucubin showing attenuation of CP-induced oxidative stress in kidneys. Moreover, aucubin reduced increased renal expression of cleaved caspase-3 and -9 and decreased poly (ADP-ribose) polymerase (PARP) cleavage, indicating the attenuation of CP-induced apoptosis in kidneys. Mechanistically, aucubin suppressed the activation of several signalling pathways involved in inflammation and apoptosis, including the immunohistochemically determined nuclear localisation of nuclear factor-kappa B (NF-κB) and by western blot analysis of signal transducer and activator of transcription 3 (STAT3), Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a) showing that aucubin suppresses CP-induced renal inflammation and suppresses CP-induced activation of ERK1/2, Akt/ mTOR, and FOXO3a signalling. The parenteral application was marginally but statistically more effective in reducing CP-induced kidney injury than oral administration. These findings suggest that aucubin acts as a protective agent against CP-induced nephrotoxicity, which should be further investigated.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA