Title : Biochemical indicators of the effect of tetrahydrocannabinol against cytostatic irinotecan toxicity in a model of mice with syngeneic colon tumor
Irinotecan is one of the most commonly used cytostatics for the treatment of advanced colon cancer. The incidence of this type of cancer is a growing public health problem in all developed countries. Side effects caused by the use of irinotecan significantly reduce the quality of life of treated patients. Although they can be reduced to some extent by taking supportive therapies under medical supervision, patients treated with irinotecan often take various dietary supplements to reduce the effects of acute and delayed cholinergic syndrome and improve the general condition of the body. Due to the growing public opinion about the high antitumor potential of products with Δ-9-tetrahydrocannabinol (THC), for which the relevant scientific literature does not offer credible evidence, some cancer patients often take unregistered preparations containing up to 90% THC. Previous research has shown that the use of some bioactive substances can cause adverse interactions and disrupt the metabolism and pharmacokinetics of cytostatics. Considering the fact that the metabolic pathways of irinotecan and THC in the body overlap: (i) at the level of the first two phases of metabolic biotransformation in which the enzymes CYP3A4 and UDP-glucuronyltransferase are key; (ii) bacterial β-glucuronidase is involved in the metabolism of SN-38 (the active form of irinotecan) and THC; (iii) both compounds have an inhibitory effect on the enzyme acetylcholinesterase (AChE), it is assumed that the intake of high concentrations of THC in the body during treatment with irinotecan could worsen the side effects. This lecture will present an investigation on the potential interactions of cytostatic irinotecan and THC in an experimental mouse model in terms of biochemical toxicity indicators (cholinesterase activity and markers of oxidative stress). Given the general lack of knowledge about the potential interactions of the test compounds, and the fact that the use of THC preparations is popular, results of conducted study could provide a number of insights useful for practitioners in medical toxicology and possible application in clinical practice.