Abstract
BackgroundOxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal ischemia/reperfusion (IR) injury. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress.Materials and MethodsBilateral renal warm IR was induced in male C57BL/6 mice after ethanol or saline administration. Blood ethanol concentration, kidney function, histological damage, inflammatory infiltration, cytokine production, oxidative stress, antioxidant capacity and Aldehyde dehydrogenase (ALDH) enzymatic activity were assessed to evaluate the impact of antecedent ethanol exposure on IR-induced renal injury.ResultsAfter bilateral kidney ischemia, mice preconditioned with physiological levels of ethanol displayed significantly preserved renal function along with less histological tubular damage as manifested by the reduced inflammatory infiltration and cytokine production. Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities. Our studies further demonstrated that ethanol pretreatment specifically increased ALDH2 activity, which then suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE).ConclusionsOur results provide first line of evidence indicating that antecedent ethanol exposure can provide protection for kidneys against IR-induced injury by enhancing antioxidant capacity and preventing lipid peroxidation. Therefore, ethanol precondition and ectopic ALDH2 activation could be potential therapeutic approaches to prevent renal IR injury relevant to various clinical conditions.
Highlights
Ischemia/reperfusion (IR), a common pathological process, occurs under various clinical conditions such as trauma, hypovolemic shock, sepsis, and most importantly renal transplantation
Mechanistic studies revealed that precondition of mice with physiological levels of ethanol 3 h before IR induction enhanced antioxidant capacity characterized by significantly higher superoxidase dismutase (SOD) activities
Our studies further demonstrated that ethanol pretreatment increased Aldehyde Dehydrogenase 2 (ALDH2) activity, which suppressed lipid peroxidation by promoting the detoxification of Malondialdehyde (MDA) and 4-hydroxynonenal (HNE)
Summary
Ischemia/reperfusion (IR), a common pathological process, occurs under various clinical conditions such as trauma, hypovolemic shock, sepsis, and most importantly renal transplantation. A common event caused by excessive production of reactive oxygen species (ROS) during IR process, is a critical factor implicated in both direct and subsequent cellular damage [9,10]. Lipid peroxidation acts as one of the most important sources of oxidative stress, and previous studies have already demonstrated evidence indicating its implication in renal IR injury [13,14]. It is an autocatalytic mechanism resulting in oxidative destruction of cellular membranes associated with the production of toxic, reactive aldehydic metabolites and cell death [15]. The purpose of current study is to demonstrate the effect of antecedent ethanol exposure on IR-induced renal injury by modulation of oxidative stress
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