Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain following a single oral dose of caffeine
- PMID:8261611
- DOI: 10.1016/0165-3806(93)90023-4
Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain following a single oral dose of caffeine
Abstract
This paper describes the disposition of caffeine and its metabolites, theophylline, theobromine and paraxanthine in the 20-day fetal and adult brains following a single maternal dose of 5 or 25 mg/kg caffeine. Brains and plasma were collected 5 and 30 min, and 1, 3, 8 and 24 h after dosing. It was found that fetal and adult caffeine AUC (area under the concentration-time curve) values did not differ between the brain and plasma at either dose. Caffeine's primary metabolites theophylline, theobromine and paraxanthine did, however, accumulate in the fetal brain at both doses resulting in a 3-fold increase in brain metabolite exposure compared to fetal circulatory levels. In contrast to the fetus, metabolite AUC values after a dose of 25 mg/kg were found to be lower in the brains of adults compared with plasma. This suggests that caffeine's primary metabolites might be selectively excluded from the adult brain. In conclusion we have shown that, unlike the adult, the fetal rat brain accumulates theophylline, theobromine and paraxanthine when exposed to caffeine doses comparable to those attainable by normal human consumption. Since many aspects of caffeine metabolism are similar in the rat and human, we suggested that particular attention should be paid to the consumption of caffeine during pregnancy.
Similar articles
- Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.Pollard I, Williamson S, Downing J, Scaramuzzi R.Pollard I, et al.J Vet Pharmacol Ther. 1996 Apr;19(2):113-7. doi: 10.1111/j.1365-2885.1996.tb00022.x.J Vet Pharmacol Ther. 1996.PMID:8735418
- Comparative pharmacokinetics of caffeine and three metabolites in clinically normal horses and donkeys.Peck K, Mealey KL, Matthews NS, Taylor TS.Peck K, et al.Am J Vet Res. 1997 Aug;58(8):881-4.Am J Vet Res. 1997.PMID:9256975
- High-performance liquid chromatographic separation of caffeine, theophylline, theobromine and paraxanthine in rat brain and serum.Parra P, Limon A, Ferre S, Guix T, Jane F.Parra P, et al.J Chromatogr. 1991 Sep 18;570(1):185-90. doi: 10.1016/0378-4347(91)80214-w.J Chromatogr. 1991.PMID:1797825
- The toxicology of cocoa and methylxanthines: a review of the literature.Tarka SM Jr.Tarka SM Jr.Crit Rev Toxicol. 1982;9(4):275-312. doi: 10.3109/10408448209037495.Crit Rev Toxicol. 1982.PMID:6765610Review.
- Methylxanthines: toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines.Stavric B.Stavric B.Food Chem Toxicol. 1988 Aug;26(8):725-33. doi: 10.1016/0278-6915(88)90073-7.Food Chem Toxicol. 1988.PMID:3058562Review.
Cited by
- Retinoic Acid Signaling Plays a Crucial Role in Excessive Caffeine Intake-Disturbed Apoptosis and Differentiation of Myogenic Progenitors.Wu N, Li Y, He X, Lin J, Long D, Cheng X, Brand-Saberi B, Wang G, Yang X.Wu N, et al.Front Cell Dev Biol. 2021 Mar 9;9:586767. doi: 10.3389/fcell.2021.586767. eCollection 2021.Front Cell Dev Biol. 2021.PMID:33791291Free PMC article.
- Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats.Soellner DE, Grandys T, Nuñez JL.Soellner DE, et al.Behav Brain Res. 2009 Dec 14;205(1):191-9. doi: 10.1016/j.bbr.2009.08.012. Epub 2009 Aug 15.Behav Brain Res. 2009.PMID:19686781Free PMC article.
- Maternal caffeine intake during pregnancy is associated with birth weight but not with gestational length: results from a large prospective observational cohort study.Sengpiel V, Elind E, Bacelis J, Nilsson S, Grove J, Myhre R, Haugen M, Meltzer HM, Alexander J, Jacobsson B, Brantsaeter AL.Sengpiel V, et al.BMC Med. 2013 Feb 19;11:42. doi: 10.1186/1741-7015-11-42.BMC Med. 2013.PMID:23421532Free PMC article.
- Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease.Camandola S, Plick N, Mattson MP.Camandola S, et al.Neurochem Res. 2019 Jan;44(1):214-227. doi: 10.1007/s11064-018-2492-0. Epub 2018 Feb 8.Neurochem Res. 2019.PMID:29417473Free PMC article.Review.
- A recursive-partitioning model for blood-brain barrier permeation.Mente SR, Lombardo F.Mente SR, et al.J Comput Aided Mol Des. 2005 Jul;19(7):465-81. doi: 10.1007/s10822-005-9001-7. Epub 2005 Dec 6.J Comput Aided Mol Des. 2005.PMID:16331406
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Medical