Dl-3-n-butylphthalide pretreatment attenuates renal ischemia/reperfusion injury

Abstract

Background: Renal ischemia reperfusion injury (IRI) has become a growing concern in clinical practice with high morbidity and mortality rates. There is currently no effective prophylactic regimen available to prevent its occurrence and to improve its clinical prognosis. Dl-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Little is known about its role in preventing kidney injury.

Methods: The kidneys of male C57BL/6J mice were subjected to 33 min of ischemia followed by 24 h of reperfusion. NBP was administered by gavage prior to surgery. The reno-protective effect of NBP was evaluated by serum creatinine, kidney injury markers and renal pathological changes. Furthermore, the inflammation, oxidative stress, and apoptosis markers in kidney tissue were examined. In vitro, HK2 cells were treated prophylactically with NBP and then exposed to hypoxia/reoxygenation (H/R). Cell viability and apoptosis related protein were quantified to verify the protective effect of NBP. Pro-inflammation genes expression as well as ROS generation were further investigated also.

Results: NBP pretreatment significantly improved renal dysfunction and alleviated pathological injury, renal inflammation response, oxidative stress and cell apoptosis. Consistently, NBP attenuated H/R induced increases in ROS, pro-inflammatory genes expression, apoptosis and cleaved caspase-3 levels in HK2 cells.

Conclusion: Our promising results validated for the first time that NBP could ameliorate renal IRI via attenuating inflammation, oxidative stress, and apoptosis, which indicated that NBP might be a good candidate against AKI.

Keywords: Acute kidney injury (AKI); Apoptosis; Dl-3-n-butylphthalide (NBP); Inflammation; Ischemia reperfusion injury (IRI); Oxidative stress.