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 Δ⁹-tetrahydrocannabinol (Δ⁹-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-Δ⁹-THC (THC-COOH) excretion with concomitant irinotecan treatment or without. Both irinotecan and irinotecan + Δ⁹-THC administration caused moderate leukopenia but a greater decrease in leukocyte count was observed in the irinotecan + Δ⁹-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 + Δ⁹-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.

由于对潜在吸食大麻制剂作为联合用药的癌症管理毒性作用减缓研究的极大兴趣，我们调查的影响Δ ⁹四氢大麻酚（Δ ⁹ -THC）来调节伊立替康（CPT-11）诱导的毒性。用单一伊立替康腹膜内剂量，100 mg / kg体重（bw）或伊立替康联合THC（7 mg / kg bw，口服）治疗雄性Wistar大鼠，重复给药1、3和7天）。给药后最多7天获得连续血样，并分析其全血细胞计数和生化参数（肝酶，肌酐，炎性标志物和脂质状态）。串行尿样品收集在第一个24小时监测THC的时程代谢物11-NOR -9-羧基- Δ ⁹ -THC（THC-COOH）排泄伴随伊立替康治疗或没有。伊立替康和伊立替康+Δ ⁹ -THC给药引起的白细胞减少症适中但在伊立替康+Δ中观察到白细胞计数一个更大的下降⁹与单一伊立替康相比，经-THC治疗表明联合治疗具有更高的细胞毒性作用。伊立替康治疗可在大鼠无腹泻症状且循环促炎介质不增加的情况下诱导其升高天冬氨酸转氨酶（AST）。有趣的是，AST的仰角在伊立替康+Δ中没有观察到⁹ -THC基。伊立替康+ THC组中的肌酐校正尿THC-COOH浓度以时间依赖性方式高于仅THC组，这表明大麻素和伊立替康之间可能存在早期相互作用。需要进一步的研究来研究大麻素的作用，特别是对血液毒性，伊立替康代谢及其在伊立替康治疗的宿主中可能作为可修饰因子的作用。