Contents lists available at ScienceDirect Prostaglandins, Leukotrienes and Essential Fatty Acids journal homepage: www.elsevier.com/locate/plefa Impact of conjugated linoleic acid administered to rats prior and after carcinogenic agent on arachidonic and linoleic acid metabolites in serum and tumors Małgorzata Jelińska a, ⁎ , Agnieszka Białek a , Iwona Gielecińska b , Hanna Mojska b , Andrzej Tokarz a a Department of Bromatology, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland b Department of Metabolomics, National Food and Nutrition Institute, Powsińska 61/63, 02-903 Warsaw, Poland ARTICLE INFO Keywords: Hydroxyeicosatetraenoic acids 15- 12- and 5-HETE Hydroxyoctadecadienoic acids 13- and 9-HODE Prostaglandin E 2 Conjugated linoleic acid ABSTRACT The objective of the study was to assess the influence of conjugated linoleic acid (CLA) daily supplementation prior and after carcinogenic agent on the concentrations of eicosanoids – metabolites of arachidonic acid (15-, 12- or 5-hydroxyeicosatetraenoic acids (15-, 12-, 5-HETE), prostaglandin E 2 (PGE 2 )) and linoleic acid (13- or 9- hydroxyoctadecadienoic acids (13-, 9-HODE)) in rat serum and 7,12-dimethylbenz[a]anthracene (DMBA)-in- duced tumors. Female rats were randomised into six groups, receiving 1% or 2% Bio-C.L.A or plant oil since the 37th day of life throughout the whole experiment. Some rats (50-day-old) were administered DMBA to induce tumors. Eicosanoids were analyzed with LC-MS/MS. The study indicated that CLA supplemented daily to rats prior and after carcinogen administration affected concentrations of arachidonic and linoleic acid metabolites in rat serum and induced tumors. However, ratios of eicosanoids exerting opposite activities (e.g. 12-HETE/15- HETE) appear to act as more precise factors reflecting pathological changes in an organism than individual compounds. 1. Introduction Epidemiological data indicate that breast cancer belongs to the leading causes of death [1]. Various environmental factors are thought to play a significant role in carcinogenesis and nutrition is of particular importance. Among all nutritive compounds polyunsaturated fatty acids (PUFA) from n-6 and n-3 families appear to influence this process directly, by cytotoxic activity of some fatty acids to cancer cells, or indirectly, by the action of their derivatives [2–4]. PUFA metabolites belong to several groups according to carbon number in the precursor fatty acid. Eicosanoids are locally acting, bioactive derivatives, initially of arachidonic acid (AA), dihomo-gamma-linolenoic acid (DGLA) and eicosapentaenoic acid (EPA), of 20 carbons in the chain, synthesized on cyclooxyganase (COX) and lipoxygenase (LOX) pathways. Octadeca- noids and docosanoids are similar metabolites of linoleic acid (LA, C18:2 n-6) and docosahexaenoic acid (DHA, C22:6), respectively [5,6]. However, nowadays the last two groups are more and more frequently included to eicosanoids, which mean COX and LOX metabolites of PUFA generally [7]. In that meaning we use “eicosanoids” in the pre- sent paper. Synthesized on the COX pathway arachidonic acid metabolites be- long to well-studied compounds, crucial for physiological and patho- logical processes, including cancer. Prostaglandin E 2 (PGE 2 ) is con- sidered a pro-inflammatory mediator stimulating cell proliferation, migration and apoptosis [8]. Its high amounts were found in some tu- mors, e.g. of digestive tract or breast [9]. Animal studies indicated that LA content in the diet influenced the increase of PGE 2 concentration in tissues. However, high PGE 2 concentrations may occur together with a low cancer incidence in rats and conversely low levels appear with the high cancer risk [10]. Contrary to arachidonic acid COX derivatives, hydroxyeicosatetraenoic acids (HETE) produced on the LOX pathway were initially regarded as biologically inactive. Presently, they are considered important lipid mediators participating in many patholo- gical processes, such as inflammation and diseases associated with it – hypertension, atherosclerosis, reumatoid arthritis and cancer [11]. 12- and 5-hydroxyeicosatetraenoic acids (12- and 5-HETE) influence http://dx.doi.org/10.1016/j.plefa.2017.08.013 Received 20 March 2017; Received in revised form 10 July 2017; Accepted 21 August 2017 ⁎ Corresponding author. E-mail address: malgorzata.jelinska@wum.edu.pl (M. Jelińska). Abbreviations: AA, arachidonic acid; CLA, conjugated linoleic acid; COX, cyclooxygenase; EPA, eicosapentaenoic acid; DGLA, dihomo-gamma-linolenoic acid; DHA, docosahexaenoic acid; DMBA, 7,12-dimethylbenz[a]anthracene; FLAP, 5-lipoxygenase activating protein; HETE, hydroxyeicosatetraenoic acid; HODE, hydroxyoctadecadienoic acid; LA, linoleic acid; LC- MS/MS, liquid chromatography with tandem mass spectrometry; LOX, lipoxygenase; 5-oxo-ETE, 5-oxo-eicosatetraenoic acid; PGE 2 , prostaglandin E2; PPARγ, peroxisome proliferator- activated receptor gamma; PUFA, polyunsaturated fatty acids; SEM, standard error of mean; TXA 2 , thromboxane A2 Prostaglandins, Leukotrienes and Essential Fatty Acids 126 (2017) 1–8 0952-3278/ © 2017 Elsevier Ltd. All rights reserved. MARK