FIGURE 4.

Effects of coffee and caffeic acid (CA) + caffeic acid phenylethyl ester (CAPE) pretreatment on UGT activity, aminotransferases and leukopenia. (a) UGT enzyme activity against a proluciferin substrate was determined using UGT‐Glo™ Assay (Promega). UGT activity was significantly induced by coffee and CA + CAPE pretreatment in htgUGT1A‐WT and single nucleotide polymorphism (SNP) mice. Columns represent mean ± SD from five individual mice per group. (b) SN‐38 glucuronide formation analysed by LC‐MS/MS measurements (urine) was significantly increased by coffee and CA + CAPE pretreatment in both mouse lines (values represent mean of n = 10 mice per group ±SD). (c,d) Protective effects of coffee and CA + CAPE pretreatment on irinotecan‐induced elevation of aminotransferases and leukopenia (values represent mean of n = 10 mice per group ±SD). (c) ALT and AST levels were reduced by coffee and CA + CAPE pretreatment in irinotecan‐injected htgUGT1A mice. (d) Irinotecan‐induced leukopenia was reversed by pretreatment with coffee and CA + CAPE. Significance was determined as indicated by lines. *P < 0.05; n.s., non‐significant