BackgroundThe oxidative modifications of bioactive macromolecules have important roles in carcinogenesis. Of particular interest are lipid peroxidation products, which are involved in the activation of Nrf2 and endocannabinoids that affect cancer progression.MethodsIn lung cancer tissues (squamous cell lung carcinoma - SCC and adenocarcinoma - AC), the glutathione peroxidase and catalase activity and glutathione level, together with the expression of Nrf2 and its activators/inhibitors were estimated. The oxidative modifications of DNA (8-hydroxy-2′-deoxyguanosine and N7-methylguanine), endocannabinoids (anandamide and 2- arachidonylglyceriol), their receptors (CB1/2, TRV1, GPR55), phospholipid fatty acids (arachidonic, linoleic and docosahexaenoic), and reactive aldehydes (4-hydroxynonenal, 4-oxononenal and malondialdehyde) were determined.ResultsTumour tissues showed lower antioxidant capacity than healthy tissues, which was accompanied by lower levels of fatty acids and higher levels of reactive aldehydes. Disturbances in antioxidant capacity and enhanced DNA oxidative modifications were observed in 88% of AC patients and 81% of SCC patients. The 4-hydroxynonenal-Histidine adducts were detected in the necrotic and stromal cells in all tumours. These findings were associated with the enhanced Nrf2 activity, especially in AC. The strong difference between the cancer subtypes was evident in the levels of endocannabinoids, with an increase in 89% of SCC and a decrease in 85% of AC patients being observed. Additionally, the increase in the expression of CB1/2 receptors was observed only in 82% of AC, while the expression of VR1 and GPR55 was enhanced in 79% of SCC and 82% of AC patients.ConclusionsThis study shows significant differences in the redox status, Nrf2 pathway and endocannabinoid system between SCC and AC tissues. Understanding the relation between the various lipid mediators and antioxidants in different lung cancer subtypes may be beginning for further research on the effective anticancer therapy.

Primary and secondary hypertension is associated with kidney redox imbalance resulting in enhanced reactive oxygen species (ROS) and enzymes dependent phospholipid metabolism. The fatty acid amide hydrolase inhibitor, URB597, modulates the levels of endocannabinoids, particularly of anandamide, which is responsible for controlling blood pressure and regulating redox balance. Therefore, this study aimed to compare the effects of chronic URB597 administration to spontaneously hypertensive rats (SHR) and rats with secondary hypertension (DOCA-salt rats) on the kidney metabolism associated with the redox and endocannabinoid systems. It was shown fatty acid amide hydrolase (FAAH) inhibitor decreased the activity of ROS-generated enzymes what resulted in a reduction of ROS level. Moreover varied changes in antioxidant parameters were observed with tendency to improve antioxidant defense in SHR kidney. Moreover, URB597 administration to hypertensive rats decreased pro-inflammatory response, particularly in the kidneys of DOCA-salt hypertensive rats. URB597 had tendency to enhance ROS-dependent phospholipid oxidation, estimated by changes in neuroprostanes in the kidney of SHR and reactive aldehydes (4-hydroxynonenal and malondialdehyde) in DOCA-salt rats, in particular. The administration of FAAH inhibitor resulted in increased level of endocannabinoids in kidney of both groups of hypertensive rats led to enhanced expression of the cannabinoid receptors type 1 and 2 in SHR as well as vanilloid receptor 1 receptors in DOCA-salt rats. URB597 given to normotensive rats also affected kidney oxidative metabolism, resulting in enhanced level of neuroprostanes in Wistar Kyoto rats and reactive aldehydes in Wistar rats. Moreover, the level of endocannabinoids and cannabinoid receptors were significantly higher in both control groups of rats after URB597 administration.In conclusion, because URB597 disturbed the kidney redox system and phospholipid ROS-dependent and enzymatic-dependent metabolism, the administration of this inhibitor may enhance kidney disorders depending on model of hypertension, but may also cause kidney disturbances in control rats. Therefore, further studies are warranted.

The mechanisms of biological activity of commonly used natural compounds are constantly examined. Therefore, the aim of this study was to compare ascorbic acid efficacy in counteracting the consequences of UV and hydrogen peroxide treatment on lipid mediators and their regulative action on antioxidant abilities. Skin fibroblasts exposed to UVA and UVB irradiation, treated with hydrogen peroxide and ascorbic acid. The redox system was estimated through reactive oxygen species (ROS) generation (electron spin resonance spectrometer) and antioxidants level/activity (HPLC/spectrometry) which activity was evaluated by the level of phospholipid metabolites: 4-hydroxynonenal, malondialdehyde, 8-isoprostanes and endocannabinoids (GC/LC-MS) in the human skin fibroblasts. Protein and DNA oxidative modifications were also determined (LC). The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), its activators and inhibitors as well as pro/anti-apoptotic proteins and endocannabinoid receptors was examined (Western blot) and collagen metabolism was evaluated by collagen biosynthesis and prolidase activity (spectrometry). UVA and UVB irradiation and hydrogen peroxide treatment enhanced activity of xanthine and NADPH oxidases resulting in ROS generation as well as diminution of antioxidant phospholipid protection (glutathione peroxidase-glutathione-vitamin E), what led to increased lipid peroxidation and decreased endocannabinoids level. Dysregulation of cannabinoid receptors expression and environment of transcription factor Nrf2 caused apoptosis induction. Ascorbic acid partially prevented ROS generation, antioxidant capacity diminution and endocannabinoid systems disturbances but only slightly protected macromolecules such as phospholipid, protein and DNA against oxidative modifications. However, ascorbic acid significantly prevented decrease in collagen type I biosynthesis. Ascorbic acid in similar degree prevents UV (UVA and UVB) and hydrogen peroxide-dependent redox imbalance. However, this antioxidant cannot efficiently protect cellular macromolecules and avert metabolic dysregulation leading to apoptosis.

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