Abstract
Low-dose alcohol possesses multiple bioactivities. Accordingly, we investigated the protective effect and related molecular mechanism of low-dose alcohol against acute stress- (AS-) induced renal injury. Herein, exhaustive swimming for 15 min combined with restraint stress for 3 h was performed to establish a rat acute stress model, which was verified by an open field test. Evaluation of renal function (blood creatinine and urea nitrogen), urine test (urine leukocyte esterase and urine occult blood), renal histopathology, oxidative stress, inflammation, and apoptosis was performed. The key indicators of the cytochrome P450 (CYP) 4A1/20-hydroxystilbenetetraenoic acid (20-HETE) pathway, cyclooxygenase (COX)/prostaglandin E2 (PGE2) pathway, and leukotriene B4 (LTB4)/leukotriene B4 receptor 1 (BLT1) pathway were measured by real-time PCR and ELISA. We found that low-dose alcohol (0.05 g/kg, i.p.) ameliorated AS-induced renal dysfunction and histological damage. Low-dose alcohol also attenuated AS-induced oxidative stress and inflammation, presenting as reduced malondialdehyde and hydrogen peroxide formation, increased superoxide dismutase and glutathione activity, and decreased myeloperoxidase, interleukin-6, interleukin-1β, and monocyte chemoattractant protein-1 levels (P < 0.05). Moreover, low-dose alcohol alleviated AS-induced apoptosis by downregulating Bax and cleaved caspase 3 protein expression and reduced numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end label-positive cells (P < 0.01). Correlation analysis indicated that 20-HETE was strongly correlated with oxidative stress, while LTB4 was strongly correlated with inflammation. Low-dose alcohol inhibited AS-induced increases in CYP4A1, CYP4A2, CYP4A3, CYP4A8, and BLT1 mRNA levels and LTB4 and 20-HETE content (P < 0.01). Interestingly, low-dose alcohol had no effect on COX1 or COX2 mRNA expression or the concentration of PGE2. Furthermore, low-dose alcohol reduced calcium-independent phospholipase A2 mRNA expression, but did not affect secreted phospholipase A2 or cytosolic phospholipase A2 mRNA expression. Together, these results indicate that low-dose alcohol ameliorated AS-induced renal injury by inhibiting CYP4A/20-HETE and LTB4/BLT1 pathways, but not the COX/PGE2 pathway.
Highlights
Stress, commonly occurring in daily life, is a triggering or aggravating factor of many diseases that seriously threaten public health [1]
The current study has demonstrated that low-dose alcohol (0.05 g/kg), corresponding to 0.25 standard daily drinks (National Institutes of Health definition; a 12-ounce bottle or can of beer containing 5% alcohol, a 5-ounce glass of table wine containing 12% alcohol, or a 1.5-ounce shot of liquor or spirits containing 40% alcohol for a person weighing 70 kg), has a protective effect on acute stress- (AS-)induced renal injury, manifested by restoration of renal dysfunction and reduced levels of leukocyte esterase (LEU) and BLD
Our findings revealed that the COX/prostaglandin E2 (PGE2) metabolic pathway was not activated in the kidney of acute stress (AS) rats, a result that may stem from the application of different experimental models
Summary
Commonly occurring in daily life, is a triggering or aggravating factor of many diseases that seriously threaten public health [1]. Accumulating evidence indicates that acute stress (AS) is deleterious to the body’s organs and systems [2, 3]. Approximately 1.7 million deaths are attributed to acute injury of the kidney, one of the organs vulnerable to AS [4]. To date, understanding of the etiopathogenesis and effective preventive treatments for AS-induced renal injury remain limited. Exploring the exact mechanism of AS-induced renal injury and development of effective preventive therapeutics is urgently needed. A recent study implicated oxidative stress and apoptosis in AS-induced renal injury [5].
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