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

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.