Abstract
Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.
Highlights
Eicosanoids, metabolites derived from arachidonic acid (ARA), have well-established roles in renal physiological and pathophysiological functions [1]
Huang et al reported that interleukin (IL)-1 rapidly stimulates the release of phospholipase A2 (PLA2) activity-dependent ARA and activates mesangial cells via the Jun N-terminal/stress-activated protein kinase (JNK/SAPK) signaling pathway [6]
Since ARA is known to be involved in inflammation processes as described above, the present study aimed to investigate whether ARA administration decreases kidney function in the aged rats via inflammation
Summary
Eicosanoids, metabolites derived from arachidonic acid (ARA), have well-established roles in renal physiological and pathophysiological functions [1]. Nonsteroidal anti-inflammatory drugs cause fluid and electrolyte disorders, acute renal dysfunction, nephrotic syndrome/interstitial nephritis, and renal papillary necrosis [3,4,5] These reports indicate that eicosanoids are important mediators formaintaining renal function. The effects of tumor necrosis factor-α (TNF-α) on ion transport are related to the induction of COX-2-dependent PGE2 synthesis [9]. These results indicate that endogenous ARA released by inflammatory cytokines and ROS are involved in inflammatory processes in the kidney. Exogenous ARA but not eicosanoids increases IL-1-dependent ARA release by human embryonic kidney 293 cells via cPLA2 and sPLA2 [10]; ARA and its precursor, linoleic acid (LA), directly stimulates the JNK/ SAPK pathway [6]. We measured the levels of renal eicosanoids and docosanoids using liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)
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