Abstract
The liver is a key metabolic organ that is particularly sensitive to environmental factors, including UV radiation. As UV radiation induces oxidative stress and inflammation, natural compounds are under investigation as one method to counteract these consequences. The aim of this study was to assess the effect of topical application of phytocannabinoid-cannabidiol (CBD) on the skin of nude rats chronically irradiated with UVA/UVB, paying particular attention to its impact on the liver antioxidants and phospholipid metabolism. The results of this study indicate that CBD reaches the rat liver where it is then metabolized into decarbonylated cannabidiol, 7-hydroxy-cannabidiol and cannabidiol-glucuronide. CBD increased the levels of GSH and vitamin A after UVB radiation. Moreover, CBD prevents the increase of 4-hydroxynonenal and 8-iso-prostaglandin-F2α levels in UVA-irradiated rats. As a consequence of reductions in phospholipase A2 and cyclooxygenases activity following UV irradiation, CBD upregulates the level of 2-arachidonoylglycerol and downregulates prostaglandin E2 and leukotriene B4. Finally, CBD enhances decreased level of 15-deoxy-Δ-12,14-prostaglandin J2 after UVB radiation and 15-hydroxyeicosatetraenoic acid after UVA radiation. These data show that CBD applied to the skin prevents ROS- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector.
Highlights
The liver is one of the key metabolic organs in animals, and is responsible for the detoxification of many endogenous and exogenous compounds [1]
These data show that CBD applied to the skin prevents reactive oxygen species (ROS)- and enzyme-dependent phospholipid metabolism in the liver of UV-irradiated rats, suggesting that it may be used as an internal organ protector
Phospholipids containing polyunsaturated fatty acids (PUFAs) are susceptible to the action of reactive oxygen species (ROS), which promote peroxidation based on the classic chain reaction mechanism, resulting in the generation of low-molecular-weight, reactive α,β-unsaturated aldehydes and/or cyclic derivatives such as isoprostanes or neuroprostanes depending on the type of oxidation of the PUFAs underwent [5,6]
Summary
The liver is one of the key metabolic organs in animals, and is responsible for the detoxification of many endogenous and exogenous compounds [1] It is the site of the phospholipid metabolism, which, along with cholesterol, is the main components of biological membranes [2], whose phospholipid bilayers perform important structural functions, separating the cell contents from the surrounding environment, creating subcellular organelles and providing platforms for various cell processes [3]. Phospholipids containing polyunsaturated fatty acids (PUFAs) are susceptible to the action of reactive oxygen species (ROS), which promote peroxidation based on the classic chain reaction mechanism, resulting in the generation of low-molecular-weight, reactive α,β-unsaturated aldehydes and/or cyclic derivatives such as isoprostanes or neuroprostanes depending on the type of oxidation of the PUFAs underwent [5,6]. Phospholipids are substrates for the generation of bioactive molecules including endocannabinoids and eicosanoids that are involved in signal transduction [7,8]
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