Hydroxytyrosol inhibits apoptosis in ischemia/reperfusion-induced acute kidney injury via activating Sonic Hedgehog signaling pathway.

Abstract

OBJECTIVE:

Acute kidney injury (AKI) is a common critical illness in clinic, which seriously threatens the life of patients. The aim of this study was to validate the anti-apoptotic effect of hydroxytyrosol (HT) in ischemia/reperfusion (I/R)-induced AKI.

MATERIALS AND METHODS:

The cell model of AKI was established by hypoxia/reoxygenation (H/R), and the animal model of AKI was established by I/R. The apoptosis was observed by Caspase-3 activity assay, flow cytometry and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. Cell viability was detected by cell counting kit-8 (CCK-8) assay. Protein expression was measured by Western blot and mRNA level was analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Renal function was assessed by measuring serum creatinine (Cr) and blood urea nitrogen (BUN).

RESULTS:

H/R induced apoptosis of HK-2 cells and reduced cell viability. When HK-2 cells were pretreated with HT, apoptosis was markedly inhibited, and cell viability was greatly increased. In addition, HT could inhibit I/R-induced apoptosis of rat kidney cells and could notably improve rat kidney function. H/R promoted Sonic Hedgehog (SHH) expression in HK-2 cells, while HT treatment further enhanced SHH expression. Similarly, I/R induces SHH expression in kidney tissue, and HT could further promote SHH expression.

CONCLUSIONS:

These results indicated that HT could inhibit apoptosis in I/R-induced AKI via activating SHH signaling pathway.

• Authors: Q Fang, Y Zhang, D-S Jiang, Y Chen
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 24 Issue 23 Pg. 12380-12388 (12 2020) ISSN: 2284-0729 [Electronic] Italy
• PMID: 33336758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hedgehog Proteins
• 3,4-dihydroxyphenylethanol
• Phenylethyl Alcohol

Topics

• Acute Kidney Injury (drug therapy, metabolism, pathology)
• Animals
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Hedgehog Proteins (metabolism)
• Humans
• Male
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Signal Transduction (drug effects)