Safety assessment and redox status in rats after chronic exposure to cannabidiol and cannabigerol

Polanská, Hana; Petrlakova, Katerina; Papoušková, Barbora; Hendrych, Michal; Samadian, Amir; Storch, Jan; Babula, Petr; Masařík, Michal; Vacek, Jan

doi:10.1016/j.tox.2023.153460

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…Still, we observed prevention of liver enlargement in the MCT + CBD group compared to MCT rats, presumably through the beneficial effect on RV function that we have already demonstrated in our previous studies [ 9 , 10 ]. Thus, we confirmed the results of other authors where chronic (90 days) oral administration of CBD at doses of 0.66 and 1.33 mg/kg to healthy rats did not modify the most biochemical parameters (e.g., AST, ALT) and did not modify liver weight or liver/body weight ratio [ 26 ]. It correlated with no abnormalities in hepatic morphology in the CTR and CTR + CBD groups (Fig.…”

Section: Discussionsupporting

confidence: 92%

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

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Background Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH. Methods The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg). Results Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6. Conclusions The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway. Graphical abstract

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Section: Discussionsupporting

confidence: 92%

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Krzyżewska,

Baranowska-Kuczko,

Galicka

et al. 2024

Pharmacol. Rep

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“…CBD has a favorable safety profile in humans [ 18 , 20 ], in rats [ 210 ], and in dogs [ 211 ]. A recent pharmacovigilance study concluded that CBD is a safe compound that causes only rare adverse reactions [ 212 ].…”

Section: Therapeutic Evidence Involving Cbdmentioning

confidence: 99%

The Polypharmacological Effects of Cannabidiol

et al. 2023

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Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer’s disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

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“…The group of the best known and therapeutically used phytocannabinoids includes cannabidiol (CBD), which has antioxidant, anti-inflammatory, anticancer, and antibacterial properties [ 11 , 12 , 13 ]. Another representative of phytocannabinoids, a precursor of other compounds in this group, is cannabigerol (CBG) [ 14 ], which may modulate cell metabolism through mechanisms that have not been precisely clarified. The biological effects of CBD and CBG result from their structure, notably, the presence of hydroxyl groups attached to the aromatic ring (easily oxidised to the quinone form), double bonds, and the pentyl chain [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Redox and Inflammatory Signaling in Human Skin Cells Using Phytocannabinoids Applied after UVA Irradiation: In Vitro Studies

Wroński,

Jarocka-Karpowicz,

Surażyński

et al. 2024

Cells

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UVA exposure disturbs the metabolism of skin cells, often inducing oxidative stress and inflammation. Therefore, there is a need for bioactive compounds that limit such consequences without causing undesirable side effects. The aim of this study was to analyse in vitro the effects of the phytocannabinoids cannabigerol (CBG) and cannabidiol (CBD), which differ in terms of biological effects. Furthermore, the combined use of both compounds (CBG+CBD) has been analysed in order to increase their effectiveness in human skin fibroblasts and keratinocytes protection against UVA-induced alternation. The results obtained indicate that the effects of CBG and CBD on the redox balance might indeed be enhanced when both phytocannabinoids are applied concurrently. Those effects include a reduction in NOX activity, ROS levels, and a modification of thioredoxin-dependent antioxidant systems. The reduction in the UVA-induced lipid peroxidation and protein modification has been confirmed through lower levels of 4-HNE-protein adducts and protein carbonyl groups as well as through the recovery of collagen expression. Modification of antioxidant signalling (Nrf2/HO-1) through the administration of CBG+CBD has been proven to be associated with reduced proinflammatory signalling (NFκB/TNFα). Differential metabolic responses of keratinocytes and fibroblasts to the effects of the UVA and phytocannabinoids have indicated possible beneficial protective and regenerative effects of the phytocannabinoids, suggesting their possible application for the purpose of limiting the harmful impact of the UVA on skin cells.

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Safety assessment and redox status in rats after chronic exposure to cannabidiol and cannabigerol

Cited by 9 publications

References 41 publications

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats

The Polypharmacological Effects of Cannabidiol

Modulation of Redox and Inflammatory Signaling in Human Skin Cells Using Phytocannabinoids Applied after UVA Irradiation: In Vitro Studies

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