Amaranth oil in prevalent pulmonary arterial hypertension: changes in fatty acid panel and products of lipid peroxidation

Abstract

Pulmonary arterial hypertension (PAH) is a severe illness associated with the dismal prognosis. Oxidative stress (OS) plays an important role in the pathobiology of PAH and its signs are not eliminated with the long-term treatment by the PAH specific medication -sildenafil (SLD) [1,2]. Use of the compounds that improve regulation of the redox process [3] may offer benefit for the management of PAH. We studied profile of polyunsaturated fatty acids derived from phospholipids and main products of lipid peroxidation in the serum of patients with PAH, who received long-term treatment with sildenafil. Patients were divided into two groups: group 1 continued treatment with SLD; group 2 in addition to SLD received Amaranth oil (AmO) (1ml per 60 kg of body weight) for one months. Group 3 consisted of healthy volunteers who also received AmO in the above-mentioned dosing. Prevalent PAH patients were characterized by some decrease of linoleic acid (LA), arachidonic acid (AA), docosahexaenoic acid (DHA) and significant lowering of eicosapentaenoic acid (EPA) level. Interestingly that the level of gamma-linolenic acid (GLA, omega-6) increased 5.5-fold comparing to control. With continuation of SLD therapy deficit of mentioned fatty acids, especially EPA, was further progressing, however, in subjects treated with SLD only this decrease was less prominent. High levels of GLA were lowering in both groups but remained to be significantly elevated comparing to control. Supplementation with AmO reduced initially elevated levels of hydroxynonenal (HNE) by 13 %, while in patients on SLD therapy only 40% increase of HNE was observed. The level of oxononenal (ONE), which initially was 2-fold elevated, was normalized with treatment in both groups, while the levels of hydroxyhexanal and malonic dialdehyde lowered insignificantly only in group 1. Worsening of OS signs with SLD treatment in PAH was further confirmed by GSH/GSSG ratio, which was 4.95 before treatment and 10.3, 3.0 after intervention in group 1 and 2 respectively. Mild prooxidant action of AmO was confirmed in group 3 (healthy volunteers) which showed increase in phospholipid derived fatty acids (LA, AA, GLA, EPA by 20%, 54%, 20% and 103% respectively). This effects may promote development of the optimal profile of lipid-derived regulatory molecules involved in management of inflammation, immune response, and in general improved OS resistance. In addition to changes in the lipid profile, increases in HNE (by 38%), ONE (by 65%) and 2-fold lowering of GSH/GSSG were observed, which may be suggestive about the involvement of these molecules in the redox signalling. Changes in the profile of the fatty acids and products of lipid peroxidation in PAH patients and healthy volunteers are suggestive that maintaining mild prooxidant activity (hormetic reaction) may offer some benefit in the long-term management of severe chronic diseases such as PAH. The mechanisms involved in the development and maintenance of this processes need further clarification.