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DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol

1
Institute for Medical Research and Occupational Health, Zagreb HR-10001, Croatia
2
University Hospital Centre Zagreb, Zagreb HR-10000 Croatia
3
University Centre Varaždin, University North, Varaždin HR-42000, Croatia
*
Author to whom correspondence should be addressed.
These authors contribute equally to this work.
Molecules 2019, 24(8), 1560; https://doi.org/10.3390/molecules24081560
Received: 9 April 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 19 April 2019
(This article belongs to the Section Natural Products Chemistry)
Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities. View Full-Text
Keywords: acetylcholinesterase; antioxidative enzymes; brain cells; butyrylcholinesterase; genotoxicity; glutathione; comet assay; lipid peroxidation; white blood cells acetylcholinesterase; antioxidative enzymes; brain cells; butyrylcholinesterase; genotoxicity; glutathione; comet assay; lipid peroxidation; white blood cells
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Kopjar, N.; Fuchs, N.; Žunec, S.; Mikolić, A.; Micek, V.; Kozina, G.; Lucić Vrdoljak, A.; Brčić Karačonji, I. DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol. Molecules 2019, 24, 1560.

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