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• W2142154255 abstract "Polyphenolic antioxidants are being identified as cancer preventive agents. Recent studies in our laboratory have identified and defined the cancer preventive and anticarcinogenic potential of a polyphenolic flavonoid antioxidant, silymarin (isolated from milk thistle). More recent studies by us found that these effects of silymarin are due to the major active constituent, silibinin, present therein. Here, studies are done in mice to determine the distribution and conjugate formation of systemically administered silibinin in liver, lung, stomach, skin, prostate and pancreas. Additional studies were then performed to assess the effect of orally administered silibinin on phase II enzyme activity in liver, lung, stomach, skin and small bowel. For tissue distribution studies, SENCAR mice were starved for 24 h, orally fed with silibinin (50 mg/kg dose) and killed after 0.5, 1, 2, 3, 4 and 8 h. The desired tissues were collected, homogenized and parts of the homogenates were extracted with butanol:methanol followed by HPLC analysis. The column eluates were detected by UV followed by electrochemical detection. The remaining homogenates were digested with sulfatase and β-glucuronidase followed by analysis and quantification. Peak levels of free silibinin were observed at 0.5 h after administration in liver, lung, stomach and pancreas, accounting for 8.8 ± 1.6, 4.3 ± 0.8, 123 ± 21 and 5.8 ± 1.1 (mean ± SD) μg silibinin/g tissue, respectively. In the case of skin and prostate, the peak levels of silibinin were 1.4 ± 0.5 and 2.5 ± 0.4, respectively, and were achieved 1 h after administration. With regard to sulfate and β-glucuronidate conjugates of silibinin, other than lung and stomach showing peak levels at 0.5 h, all other tissues showed peak levels at 1 h after silibinin administration. The levels of both free and conjugated silibinin declined after 0.5 or 1 h in an exponential fashion with an elimination half-life ( t½ ) of 57–127 min for free and 45–94 min for conjugated silibinin in different tissues. In the studies examining the effect of silibinin on phase II enzymes, oral feeding of silibinin at doses of 100 and 200 mg/kg/day showed a moderate to highly significant ( P < 0.1–0.001, Student's t -test) increase in both glutathione S -transferase and quinone reductase activities in liver, lung, stomach, skin and small bowel in a dose- and time-dependent manner. Taken together, the results of the present study clearly demonstrate the bioavailability of and phase II enzyme induction by systemically administered silibinin in different tissues, including skin, where silymarin has been shown to be a strong cancer chemopreventive agent, and suggest further studies to assess the cancer preventive and anticarcinogenic effects of silibinin in different cancer models." @default.
• W2142154255 created "2016-06-24" @default.
• W2142154255 creator A5048444823 @default.
• W2142154255 creator A5053161337 @default.
• W2142154255 date "1999-11-01" @default.
• W2142154255 modified "2023-10-17" @default.
• W2142154255 title "Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention" @default.
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• W2142154255 doi "https://doi.org/10.1093/carcin/20.11.2101" @default.
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