TitleEffects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers.
Publication TypeJournal Article
Year of Publication2009
AuthorsJubert C, Mata J, Bench G, Dashwood R, Pereira C, Tracewell W, Turteltaub K, Williams D, Bailey G
JournalCancer Prev Res (Phila)
Volume2
Issue12
Pagination1015-22
Date Published2009 Dec
ISSN1940-6215
KeywordsAdult, Aflatoxin B1, Aged, Antimutagenic Agents, Biological Availability, Chlorophyll, Chlorophyllides, Cross-Over Studies, Dose-Response Relationship, Drug, Female, Humans, Male, Mass Spectrometry, Middle Aged, Tissue Distribution
Abstract

Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats. These findings were partially extended to humans, where CHL reduced excretion of aflatoxin B(1) (AFB(1))-DNA repair products in Chinese unavoidably exposed to dietary AFB(1). However, neither AFB(1) pharmacokinetics nor Chla effects were examined. We conducted an unblinded crossover study to establish AFB(1) pharmacokinetic parameters among four human volunteers, and to explore possible effects of CHL or Chla cotreatment in three of those volunteers. For protocol 1, fasted subjects received an Institutional Review Board-approved dose of 14C-AFB(1) (30 ng, 5 nCi) by capsule with 100 mL water, followed by normal eating and drinking after 2 hours. Blood and cumulative urine samples were collected over 72 hours, and 14C- AFB(1) equivalents were determined by accelerator mass spectrometry. Protocols 2 and 3 were similar except capsules also contained 150 mg of purified Chla or CHL, respectively. Protocols were repeated thrice for each volunteer. The study revealed rapid human AFB(1) uptake (plasma k(a), 5.05 + or - 1.10 h(-1); T(max), 1.0 hour) and urinary elimination (95% complete by 24 hours) kinetics. Chla and CHL treatment each significantly impeded AFB(1) absorption and reduced Cmax and AUCs (plasma and urine) in one or more subjects. These initial results provide AFB(1) pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models.

DOI10.1158/1940-6207.CAPR-09-0099
Alternate JournalCancer Prev Res (Phila)
PubMed ID19952359
PubMed Central IDPMC5314947
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P50 ES00210 / ES / NIEHS NIH HHS / United States
P41 RR013461 / RR / NCRR NIH HHS / United States
CA090890 / CA / NCI NIH HHS / United States
ES03850 / ES / NIEHS NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
P41RR013461 / RR / NCRR NIH HHS / United States
CA65525 / CA / NCI NIH HHS / United States