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

• Published in: Food and chemical toxicology Vol. 142; p. 111472
• Main Authors: Potočnjak, Iva, Marinić, Jelena, Batičić, Lara, Šimić, Lidija, Broznić, Dalibor, Domitrović, Robert
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2020
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - prevention & control; Administration, Oral; Animals; Antineoplastic Agents - toxicity; Apoptosis; Aucubin; Cisplatin; Cisplatin - toxicity; Forkhead Box Protein O3 - antagonists & inhibitors; Inflammation; Infusions, Parenteral; Iridoid Glucosides - administration & dosage; Iridoid Glucosides - pharmacology; Kidney; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred BALB C; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - drug effects; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Oxidative stress; Inflammation; Aucubin; Cisplatin; Kidney; Apoptosis
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111472

Aucubin is pharmacologically active natural compound which possesses numerous 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 (ip) (1.5 and 5 mg/kg) for two consecutive days, two days after ip injection of cisplatin (CP), 11 mg/kg. Treatment with aucubin by both routes of administration ameliorated histopathological changes and reduced elevated serum markers of kidney injury. CP administration increased renal expression of heme oxygenase-1 (HO-1) and 4-hydroxynonenal (4-HNE), as well as tumor necrosis factor-alpha (TNF-α), which was dose-dependently ameliorated by aucubin. Moreover, aucubin reduced increased renal expression of cleaved caspase-3 and -9 and decreased poly (ADP-ribose) polymerase (PARP) cleavage. Mechanistically, aucubin suppressed the activation of several signaling pathways involved in inflammation and apoptosis, including nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Akt, extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box O3a (FOXO3a). Parenteral application was marginally but statistically more effective in reducing CP-induced kidney injury than oral administration. The findings of this study suggest that aucubin acts as a protective agent against CP-induced nephrotoxicity, which should be further investigated.
[Display omitted]
•Cisplatin (CP)-intoxicated mice received aucubin orally or intraperitoneally.•Aucubin ameliorated histopathological changes and reduced kidney injury.•Aucubin decreased oxidative stress, apoptosis and inflammation in the kidney.•Aucubin suppressed the activation NF-κB, STAT3, Akt, ERK1/2 and FOXO3a.•Parenteral application was the most effective in reducing CP-induced kidney injury.