Oxidative Stress and Its Consequences in the Blood of Rats Irradiated with UV: Protective Effect of Cannabidiol

Biernacki, Michał; Brzóska, Małgorzata M.; Markowska, Agnieszka; Gałażyn-Sidorczuk, Małgorzata; Cylwik, Bogdan; Gęgotek, Agnieszka

doi:10.3390/antiox10060821

Cited by 16 publications

(19 citation statements)

References 104 publications

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“…The antioxidant activity of CBD results mainly from the reduction of the excessive generation of oxidants, which promotes, among other, the inhibition of ROS-dependent lipid peroxidation [ 8 , 11 , 15 ]. As a consequence, the level of highly reactive products of polyunsaturated fatty acids oxidative fragmentation such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) as well as the level of their adducts with protein is reduced [ [16] , [17] , [18] ]. Moreover, recent studies indicate that CBD supports the maintenance of proteostasis under oxidative conditions by regulating molecular signalling in the biosynthesis and degradation of proteins under different conditions, in vivo and in vitro [ 17 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

2021

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Hydrogen peroxide (H 2 O 2 ) is widely used in clinical practice due to its antiseptic properties and its ability to heal wounds. However, due to its involvement in the formation of ROS, H 2 O 2 causes several side effects, including disorders of the metabolism of skin cells and the development of chronic inflammation mediated by oxidative stress. Therefore, this study evaluated the effects of cannabidiol (CBD), a phytocannabinoid known for its antioxidant and anti-inflammatory properties, on the proteome of keratinocyte membranes exposed to H 2 O 2 . Overall, the hydrogen peroxide caused the levels of several proteins to increase, while the treatment with CBD prevented these changes. Analysis of the protein-protein interaction network showed that the significant changes mainly involved proteins with important roles in the proteasomal activity, protein folding processes (regulatory subunit of the proteasome 26S 6A, beta proteasome subunit type 1, chaperonin 60 kDa), protein biosynthesis (40S ribosomal proteins S16, S2 and ubiquitin-S27a), regulation of the redox balance (carbonyl reductase [NADPH] 1 and NAD(P)H [quinone] 1 dehydrogenase) and cell survival (14-3-3 theta protein). Additionally, CBD reduced the total amount of MDA, 4-HNE and 4-ONE-protein adducts. Therefore, we conclude that CBD partially prevents the changes induced by hydrogen peroxide by reducing oxidative stress and maintaining proteostasis networks. Moreover, our results indicate that combination therapy with CBD may bring a promising approach in the clinical use of hydrogen peroxide by preventing its pro-oxidative and pro-inflammatory effect through potential participation of CBD in membrane mediated molecular signaling.

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Section: Introductionmentioning

confidence: 99%

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

2021

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“…It was previously shown [ 20 ] that UVA/UVB irradiation of rats enhances the systemic production of ROS and lowers the antioxidant defense, which is conducive to the formation of oxidative stress. A similar situation is observed at the liver level of rats ( Figure 2 and Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…One natural compound with antioxidant and anti-inflammatory properties that has been highly researched recently is cannabidiol (CBD)—non-psychoactive phytocannabinoid [ 19 ]. In previous studies we showed that CBD after topical application penetrates into the bloodstream and is present in the blood plasma [ 20 ]. As a consequence, it is relatively quickly distributed to all organs with a good blood supply, such as the brain, heart, lungs and liver [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

2021

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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.

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“…Moreover, described self-induced CBD applications can affect in an indefinite way not only on cell metabolism but also the entire human body. The experiments on mouse and rat models showed that topically applied CBD penetrates in to the blood and is transported throughout the bloodstream 27 , 44 . Additionally, it has been shown in another animal experiment that spot application of CBD shows even greater effects comparing to its systemic distribution 45 .…”

Section: Discussionmentioning

confidence: 99%

“…According to the such a broad spectrum of CBD action, connected with its properties of penetration through biological membranes and poly-layer cells cultures 21 , 22 , as well as its possibility of infiltration from the skin into the blood 27 , it is suggested that CBD may have significant impact on the oxidative, as well as pro-inflammatory changes induces by UV radiation. Therefore, the aim of this study was to analyze the changes in the proteomic profile of plasma from chronically UVA or UVB irradiated rats and define the effect on these changes of skin topically applied CBD.…”

Section: Introductionmentioning

confidence: 99%

UV induced changes in proteome of rats plasma are reversed by dermally applied cannabidiol

Gęgotek

Atalay

2021

Sci Rep

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UV radiation is known to induce a multiple changes in the metabolism of skin-building cells, what can affect the functioning not only neighboring cells, but also, following signal transduction releasing into the blood vessels, the entire body. Therefore, the aim of this study was to analyze the proteomic disturbances occurred in plasma of chronically UVA/UVB irradiated rats and define the effect on these changes of skin topically applied cannabidiol (CBD). Obtained results showed significant changes in the expression of numerous anti-inflammatory and signaling proteins including: NFκB inhibitor, 14-3-3 protein, protein kinase C, keratin, and protein S100 after UV irradiation and CBD treatment. Moreover, the effects of UVA and UVB were manifested by increased level of lipid peroxidation products—protein adducts formation. CBD partially prevented all of these changes, but in a various degree depending on the UV radiation type. Moreover, topical treatment with CBD resulted in the penetration of CBD into the blood and, as a consequence, in direct modifications to the plasma protein structure by creating CBD adducts with molecules, such as proline-rich protein 30, transcription factor 19, or N-acetylglucosamine-6-sulfatase, what significantly changed the activity of these proteins. In conclusion, it may be suggested that CBD applied topically may be an effective compound against systemic UV-induced oxidative stress, but its effectiveness requires careful analysis of CBD's effects on other tissues of the living organism.

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Oxidative Stress and Its Consequences in the Blood of Rats Irradiated with UV: Protective Effect of Cannabidiol

Cited by 16 publications

References 104 publications

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

UV induced changes in proteome of rats plasma are reversed by dermally applied cannabidiol

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