The Effect of Apigenin on Renal Damage Induced by Aristolochic Acid I and the Involvement of Nrf2/HO-1 Pathway

ABSTRACT

Background: Aristolochic acid is naturally found in plants of the Aristolochiaceae family and possesses antitumor, antiinfection, and anti-inflammatory properties. Objectives: This study investigated the protective effect of apigenin (API) on aristolochic acid I (AAI)-induced renal damage in mice and its underlying mechanisms. Materials and Methods: Male C57BL/6J mice were assigned to the control group, model group, and API low, medium, and high-dose groups (10, 20, 40 mg/kg). On the 5th day, 2 h after administration, except for the control group, all other groups were intraperitoneally injected with AAI (10 mg/kg). Following final administration, 24-h urinary protein levels, serum creatinine (Scr), and blood urea nitrogen (BUN) levels were assessed along with hematoxylin–eosin (HE) staining of kidneys and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, as well as analysis of malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Results: When compared with the model group, mice in API treatment groups exhibited significantly reduced 24-h urinary protein levels and serum levels of Scr and BUN (p < 0.05) with an improvement in renal tissue histopathological changes and cell apoptosis as well as decreased MDA and increased SOD and GSH-Px (p < 0.05). Tumor necrosis factor alpha protein (TNF-α)/interleukin (IL)-1β/IL-6 levels showed a reduction (p < 0.05). Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were upregulated, while NF-κB/Cleaved Caspase-3 were downregulated (p < 0.01). Conclusion: API protects against renal damage induced by AAI possibly through Nrf2/HO-1 pathway, which in turn inhibits oxidative stress damage, inflammatory responses, and cell apoptosis.

KEYWORDS

• Apigenin
• aristolochic acid I
• renal damage
• nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway

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• DOI10.1177/09731296241297733Copy

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