Protective effects of ischemic pre-conditioning and boldine on unilateral renal ischemia reperfusion injury-induced brain damage: apoptotic, pyroptotic, inflammatory, and oxidative pathways

缺血预适应和博尔定对单侧肾脏缺血再灌注损伤引起的脑损伤的保护作用:凋亡、细胞焦亡、炎症和氧化途径

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Abstract

The aim of this study was to evaluate the effects of ischemic pre-conditioning and boldine on unilateral renal ischemia-reperfusion (IR) injury-induced brain damage. Thirty rats were divided into five groups (n = 6 rats per group): sham, renal IR, pre-conditioning + renal IR, boldine + renal IR, and boldine + pre-conditioning + renal IR. The ischemia groups were subjected to 45 min of left kidney ischemia and 24 h of reperfusion. Pre-conditioning consisted of three sets of 2 min of ischemia and 5 min of reperfusion. Boldine (20 mg/kg/day, i.p.) was administered for 7 d. Tissues were collected for molecular analysis and histological evaluations. Brain Bax, Bcl-2, cleaved caspase 3, Nrf2, NLRP3, and gasdermin D levels were analyzed via western blot. Interleukine (IL)-2, tumor necrosis factor-α, IL-6, and IL-10 levels were evaluated via ELISA. The levels of malondialdehyde and catalase in the kidney and brain were measured. Hematoxylin-eosin staining and p53 and NF-κB expressions in the kidney and brain were evaluated. Statistical analysis was performed using the Kruskal-Wallis test, followed by the Mann-Whitney U test with the Bonferroni correction. The decreases in apoptotic, pyroptotic, inflammatory, and oxidative markers indicated the positive effects of pre-conditioning and boldine. We concluded that pre-conditioning, like boldine, can be a potential option to ameliorate unilateral renal IR injury-induced brain damage.

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