Abstract
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.
Highlights
The worldwide use of various forms of cannabis preparations has been known for centuries. many of them are taken for recreational purposes, today we are witnessing an increased use of approved cannabis preparations for symptoms management in cancer therapies, neurological disorders and various conditions associated with chronic pain
This paper provides evidence that brain and white blood cells responded with significant increases of DNA damage much earlier than hepatocytes, at the same tested
Produced genotoxic effects in rat hepatocytes after seven days of repeated exposure, this study provides evidence that brain and white blood cells responded with significant increases of DNA damage much earlier than hepatocytes
Summary
Many of them are taken for recreational purposes, today we are witnessing an increased use of approved cannabis preparations for symptoms management in cancer therapies, neurological disorders and various conditions associated with chronic pain. Despite the accessibility of the approved medications, many patients still rely on the use of various forms of illegal crude cannabis preparations to relieve their symptoms. After 3- and 7-day treatments, THC-treated rats showed significantly increased mean values of tail length and total comet area compared to corresponding controls (Figure 1). The extent of DNA damage in brain cells of rats treated with THC for one and three consecutive days, perceived in terms of tail length and total comet area parameters, was significantly increased compared to respective controls (Figure 1)
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