Abstract
Background: Inflammation, oxidative stress, and cell death are major contributors to kidney injury following ischemia/reperfusion (I/R). Acacetin (ACA) is a natural flavonoid that many studies have shown can prevent I/R-induced damaging effects. Objectives: In the current attempt, we sought to search for the mechanisms through which ACA attenuates renal I/R. Methods: Male Balb/c mice were divided into four groups (n = 7): sham-operated group, I/R group, I/R treated with 50 mg/kg ACA group, and control group. Following 60 min ischemia, reperfusion was performed for 24 h. Administrations were done intraperitoneally daily for four consecutive days. Renal function was evaluated by measurement of creatinine. Changes in antioxidant capacity were evaluated by superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. The expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18), heme oxygenase-1 (Ho-1), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), and thioredoxin 1 (Trx1) was detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). The levels of IL-10, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) were detected by enzyme-linked immunosorbent assay (ELISA) assay. Results: Creatinine level showed a decreased value after ACA treatment; however, declined SOD and GPx activities were elevated by ACA. The increased expression of IL-1β, IL-6, and IL-18 in the I/R group was declined in ACA-receiving mice. The expression levels of genes involved in anti-oxidative response Nrf-2, Ho-1, and Trx1 were decreased remarkably in the I/R group, and it reversed in ACA-treated mice. The secretion of IL-10 was elevated in the ACA-administrated group compared to untreated animals, while the COX-2 and TNF-α proteins were decreased following ACA treatment. Conclusions: These beneficial effects of ACA suggest that oxidative stress response participates in the protective effect of ACA against renal I/R.