Hemodialysis and Plasma Oxylipin Biotransformation in Peripheral Tissue.

Tong Liu,Michael Rothe,Maik Gollasch,Inci Dogan,Julius V Kunz,Felix Knauf,Friedrich C Luft,Benjamin Gollasch

doi:10.3390/metabo12010034

Abstract

Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.

Highlights

Survival rates among end-stage renal disease (ESRD) hemodialysis (HD) patients are poor, and excess death rate is related to cardiovascular disease [1,2]
Decreased soluble epoxide hydrolase activity contributed to the release and accumulation of the cytochrome P450 (CYP) metabolites
To gain further insight into oxylipin metabolism, we evaluated the arteriovenous differences of oxylipins levels in uremic patients treated by HD treatment

Summary

Introduction

Survival rates among end-stage renal disease (ESRD) hemodialysis (HD) patients are poor, and excess death rate is related to cardiovascular disease [1,2]. Lipids are essential for many functions in the body, where they serve as integral components for cellular membranes as well as energy storage and signaling molecules [3]. Polyunsaturated fatty acids (PUFA) are metabolized by different enzymes, mainly cytochromes P450 (CYP), monooxygenase, cyclooxygenase (COX), and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways, which can produce a large superclass of biologically active substances, namely oxylipins (Figure 1). Metabolites 2022, 11, x FOR PEER REVIEW Metabolites 2022, 12, 34 2 of 19 2 of 18. AAsssseessssmmeenntt ooff ccyytotochcrhormome eP4P5045e0poexpyogxeyngaseena(sCeYP(C) YanPd) 1a2n-dan1d2-15a-nlidpox1y5g-leinpaosxeygenase (L(LOOXX))//CCYYPP(o(ommeeggaa--11))--hhyyddrrooxxyyllaasseeppaaththwwayays sininrersepsopnosnesetotohehmemodoiadliyasliysstisretartemaetmnte. WThayesmfoeltloawbotlhiteecshmanegaessuorbedserivnetdhienseLAm, eAtaAb,oElPicAp, aanthdwDaHyAs fmoleltoawboltihsme ,changes orbesseprevcetidveilny.LMAo,dAifiAe,dEfrPoAm, [a4n].d DHA metabolism, respectively.

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Results

Conclusion