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Because of the great interest for research on the potential use of cannabis preparations as co-medication for alleviation of toxic effects in cancer management, we investigated the influence of Δ-tetrahydrocannabinol (Δ-THC) to modulate irinotecan (CPT-11)-induced toxicity. Male Wistar rats were treated either with a single irinotecan intraperitoneal dose, 100 mg/kg body-weight (b.w.), or with irinotecan in combination with THC (7 mg/kg b. w., p. o., administered repeatedly for 1, 3 and 7 days). Serial blood samples were obtained up to seven days after dosing and were analyzed for complete blood count and biochemical parameters (liver enzymes, creatinine, inflammatory markers, and lipid status). Serial urine samples were collected in the first 24 h to monitor the time-course of THC metabolite 11-nor-9-carboxy-Δ-THC (THC-COOH) excretion with concomitant irinotecan treatment or without. Both irinotecan and irinotecan + Δ-THC administration caused moderate leukopenia but a greater decrease in leukocyte count was observed in the irinotecan + Δ-THC treated compared to the single irinotecan suggesting higher cytotoxic effects in combined treatment. Irinotecan treatment induced elevation of aspartate aminotransferase (AST) in rats without diarrheal symptoms and without an increase in circulating pro-inflammatory mediators. Interestingly, the elevation of AST was not observed in the irinotecan + Δ-THC group. The median creatinine-corrected urinary THC-COOH concentration was higher in the irinotecan + THC group compared to the THC-only group in a time-dependent manner, suggesting a possible early interaction between cannabinoids and irinotecan. Further studies are needed to investigate the role of cannabinoids particularly on hematological toxicity, irinotecan metabolism and their role as a possible modifiable factor among irinotecan-treated hosts.
This article was published in the following journal.
Name: Chemico-biological interactions
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Persistent detrimental effects from treatment for a condition. Included are effects from surgery such as POSTOPERATIVE COMPLICATIONS, and from DRUG THERAPY, such as CHEMICALLY INDUCED DISORDERS, or other THERAPEUTICS. Failure to attain a desired outcome from treatment for the condition is not considered an adverse effect.
Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.
The effects on gene expression that depend on the location of a gene with respect to its neighboring genes and region of chromosome. Stable position effects are sequence dependent. Variegated position effects depend on whether the gene is located in or adjacent to HETEROCHROMATIN or EUCHROMATIN.
Specific effects of drugs and substances on metabolic pathways such as those occurring through the CYTOCHROME P-450 ENZYME SYSTEM. These include effects that often result in DRUG INTERACTIONS; FOOD-DRUG INTERACTIONS; and HERB-DRUG INTERACTIONS.
Work that is the report of a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. While most clinical trials concern humans, this publication type may be used for clinical veterinary articles meeting the requisites for humans. Specific headings for specific types and phases of clinical trials are also available.
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