Influence of caffeine administered at 45°C on bone tissue development
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Department of Human Anatomy, Medical University of Lublin, Poland
Department of Biophysics, Medical University of Lublin, Poland
I Department of Radiology, Medical University of Lublin, Poland
Department of Physiotherapy, State School of Higher Education, Biała Podlaska, Poland
Corresponding author
Marek Tomaszewski   

Department of Human Anatomy, Medical University of Lublin, Poland
Ann Agric Environ Med. 2014;21(4):804-809
Introduction and objective:
Caffeine is one of the world’s most commonly ingested alkaloids which easily permeates the placenta. The teratogenic and embryotoxic influence of large doses of caffeine has been established in many experimental studies on animals. The objective of this work was to assess the influence of caffeine, administered at 45 °C, on the development of the bone tissue of rats, with particular reference to elemental bone composition using an X-ray microprobe.

Material and Methods:
The research was conducted on white rats of the Wistar strain. The fertilized females were divided into two groups: an Experimental Group (Group E) and a Control Group (Group C). The females in Group E were given caffeine orally (at 45 °C) in 30 mg/day doses from the 8th to the 21st day of pregnancy. The females in Group C were given water at the same temperature. The fetuses were used to assess the growth and mineralization of the skeleton. A qualitative analysis of the morphology and mineralization of bones was conducted using the alcian-alizarin method. For calcium and potassium analysis, an X-ray microprobe was used.

By staining the skeleton using the alcian-alizarin method, changes in 52 of Group E fetuses were observed. The frequency of the development variants in the Group E rats was statistically higher, compared with Group C.

Receiving caffeine at a higher temperature may result in different pharmacodynamics and significantly change tolerance to it. In Group E, a significant decrease in the calcium level, as well as an increase in the potassium level, was observed. The X-ray microprobe can be a perfect complement to the methods which enable determination of the mineralization of osseous tissue.

Spiller GA. The chemical components of coffee. In: Spiller GA (eds.). Progress in clinical and biological research. Tom 158. The methlyxanthine beverages and foods: chemistry, consumption and health effects. Alan R Liss, New York, 1984.p.1–47.
Gao H, Zhang Z, Wan X. Influences of charcoal and bamboo charcoal amendment on soil-fluoride fractions and bioaccumulation of fluoride in tea plants. Environ Geochem Health. 2012; 34: 551–562.
Narod SA, DeSanjose S, Victora C. Caffeine during pregnancy: a reproductive hazard? Am J Obstet Gynecol. 1991; 164: 1109–1114.
Shardein J. Chemically induced birth defects. 2nd ed. Marcel Dekker, New York, 1993.
Barone JJ, Roberts H. Caffeine consumption. Food Chem Toxicol. 1996; 34: 119–129.
Burdan F. Comparison of developmental toxity of selective and non – selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats – DFU and piroxicam study. Toxicology 2005; 211: 12–25.
Daly JW, Fredholm BB. Caffeine- an atypical drug of dependence. Drug Alcohol Depend. 1998; 51: 199–206.
Nishimura H, Nakai K. Congenital malformations in offspring of mice treated with caffeine. Proc Soc Exp Med. 1960; 104: 140–142.
Gilbert SG, Deborah CR. Somatic development of the infant monkey following in utero exposure to caffeine. Fundam Toxicol. 1991; 17: 454–465.
Food Standards Agency: Food Standards Agency publishes new caffeine advice for pregnant women. London: Food Standards Agency 2008 (access: 2012.01.14).
Hallström H, Melhus H, Glynn A, Lind L, Syvänen A-Ch, Michaëlsson K. Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study. Nutrition & Metabolism. 2010; 7: 12.
Yang DJ, Hwang LS, Lin JT. Effects of different steeping methods and storage on caffeine, catechins and gallic acid in bag tea infusions. J Chromatogr A. 2007; 1156: 312–320.
Christian MS. Test methods for assessing female reproductive and developmental toxicology. In: Hayes AW. Principles and method of toxicology. 4th ed. Taylor and Francis. Philadelphia 2001.p.1301–1381.
Christian MS, Brent RL. Teratogen update: Evaluation of the reproductive and developmental risks of caffeine. Teratology 2001; 64: 51–78.
Smith SE, McElhatton PR, Sullivan FM. Effects of administering caffeine to pregnant rats either as a single daily dose or as divided doses four times a day. Food Chem Toxicol. 1987; 25: 125–133.
Collins TFX, Welsh JJ, Black TN, Whitby KE, O’Donnell Jr. MW. Potential reversibility of skeletal effects in rats exposed in utero to caffeine. Food Chem Toxicol. 1987; 25: 647–662.
Tomaszewski M, Olchowik G, Tomaszewska M, Burdan F. X-ray microprobe to diagnosis bone tissue demineralization after caffeine administration. Folia histochemica et cytobiologica 2012; 50: 436–443.
Giannelli M, Doyle P, Roman E, Pelerin M, Hermon C. The effect of caffeine consumption and nausea on the risk of miscarriage. Paediatr Perinat Epidemiol. 2003; 17: 316–323.
Nakamoto T, Grant S, Yazdani M. The effect of maternal caffeine intake during pregnancy on mineral contents of rat bone. Res Exp Med. 1989; 189: 275–280.
Rossowska MJ, Carvajal W, Joseph F, Nakamoto T. Postnatal caffeine effects on copper, zinc and iron concentration in mam mary gland, milk and plasma of lactating dams and their offspring. Ann Nutr Metab. 1997; 41: 60–65.
Sasahara H, Cheuk SL, Wink CS, Hashimoto K, Rossowska MJ, Nakamoto T, Alteration of femoral structure in later life by chronically feeding caffeine during rapid growing period in newborn female rats. Toxicol Lett. 1994; 73: 55–64.
Sasahara H, Yamano H, Nakamoto T. Effects of maternal caffeine with zinc intake during gestation and lactation on bone development in newborn rats. Arch Oral Biol. 1990; 35: 425–430.
Wink CS, Rossowska MJ, Nakamoto T. Effects of caffeine on bone cells and bone development in fast – growing rats. Anat Rec. 1996; 246: 30–38.
Duarte PM, Marques MR, Bezerra JP, Bastos MF. The effects of caffeine administration on the early stage of bone healing and bone den sity: A histometric study in rats. Archives of oral biology. 2009; 54: 717–722.
Griggs GG, Freeman RK, Yaffe SJ. Drugs in pregnency and Lactation. 4th ed. William and Wilkins. Baltimore 1998.
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