Histopathological investigation of the Long-Term Effects of Nanoemulsion Caffeine Administration in Rats

Document Type : Original Article

Authors

1 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Zabol, Zabol, Iran.

2 h

10.22075/jvlr.2025.37523.1164

Abstract

With the expanding applications of nanoparticles, assessing their biocompatibility, particularly in vital tissues, has become increasingly important. This study aimed to investigate the histopathological effects of chronic administration of caffeine nanoemulsion at different doses on the liver, kidney, heart, brain, and testicular tissues of male Wistar rats. In this experimental study, 40 adult male rats were randomly assigned to four groups: one control group and three experimental groups receiving caffeine nanoemulsion orally at doses of 5, 15, and 30 mg/kg body weight per day for two months. At the end of the treatment period, animals were anesthetized using a combination of ketamine and xylazine, with tramadol administered for analgesia. Tissue samples were collected for histopathological examination, and blood samples were obtained to evaluate serum biochemical parameters. Histopathological analysis revealed mild vascular changes, including congestion, only in the kidney tissue of the group receiving the highest dose (30 mg/kg), with no evidence of necrosis or inflammation. All other examined tissues—liver, heart, brain, and testes—preserved their normal histological architecture, and no pathological alterations were observed. These findings suggest that caffeine nanoemulsion is relatively safe for the studied tissues at low to moderate doses. However, the observed vascular changes in the kidneys at the high dose highlight the need for further investigations, particularly regarding the long-term safety of high-dose applications.
 

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References

Anton , N ., Vandamme, T ,.(2011). Nano-emulsions and micro-emulsions: clarifications of the critical differences. Pharm Res.;28(5):978-985. doi:10.1007/s11095-010-0309-1.
Arnaud , MJ ,. (2011). The metabolism of caffeine. Food Chem Toxicol. 49(2):293-301. doi:10.1016/j.fct.2010.11.011.
Astrup A, Toubro S, Cannon S, et al (1990) . Caffeine’s metabolic effects. Am J Clin Nutr. 51(5):759-767. doi:10.1093/ajcn/51.5.759.
Barone , JJ ,.  Roberts , HR ,. (1996). Caffeine consumption. Food Chem Toxicol. 34(1):119-129. doi:10.1016/0278-6915(95)00093-3.
Benowitz , NL ,. (2010). Clinical pharmacology of caffeine. Annu Rev Med. 61:279-288. doi:10.1146/annurev.med.61.032106.115949.
Childs , E ,. Hohoff , C ,. Deckert , J ,. et al . (2008) . Caffeine-induced anxiety and genetics. Neuropsychopharmacology33(12):2791-2800. doi:10.1038/sj.npp.1301645.
Childs , E ., Hohoff , C ., Deckert , J ., Xu , K ,. et al . (2008). Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology. 33(12):2791-2800. doi:10.1038/sj.npp.1301645.
Fredholm , BB ,. Bättig , K ., Holmén , J ., et al . (1999). Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 51(1):83-133. PMID: 10049999.
Garrett , BE ., Griffiths , RR ,. (1997). The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol Biochem Behav. 57(3):533-541. doi:10.1016/S0091-3057(96)00435-2.
Guttoff , M., Saberi , AH., McClements, DJ . (2015). Formation of vitamin D nanoemulsion-based delivery systems by spontaneous emulsification: influence of lipid droplets on physicochemical properties. J Agric Food Chem.;63(4):1007-1015. doi:10.1021/jf505213t.
Heckman , MA ,. Weil , J ,. Gonzalez de Mejia , E ,. (2010). Caffeine in foods: A comprehensive review. J Food Sci.;75(3):R77-R87. doi:10.1111/j.1750-3841.2010.01561.x.
Kotta , S., Khan , AW., Pramod , K ., et al. (2012) . Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Deliv.;9(5):585-598. doi:10.1517/17425247.2012.668523.
López –Gallardo , M ., Newcombe , DS ., Craig , CR ,. (2001). Effects of caffeine and coffee consumption on plasma markers of kidney function. J Pharmacol Exp Ther. 296(2):637-642. PMID: 11160638.
Nawrot , P,.  Jordan , S ,. Eastwood , J ,. et al . (2003) . Effects of caffeine on human health. Food Addit Contam. 20(1):1-30. doi:10.1080/0265203021000007840.
Nehlig , A ,. (2010). Is caffeine a cognitive enhancer. J Alzheimers Dis. 20(Suppl 1):S85-S94. doi:10.3233/JAD-2010-091315.
Nehlig , A ., Daval , JL ., Debry , G ,. (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev. 17(2):139-170. doi:10.1016/0165-0173(92)90012-B.
Paiva , CL,.  Beserra , BT,. Reis , CE ,. et al . (2019) . Consumption of coffee or caffeine and serum concentration of inflammatory markers: A systematic review. Crit Rev Food Sci Nutr. 59(4):652-663. doi:10.1080/10408398.2017.1386159.
Sonneville-Aubrun , O ., Simonnet , JT ., L’Alloret , F ,. (2004). Nanoemulsions: a new vehicle for skincare products. Adv Colloid Interface Sci.;108-109:145-149. doi:10.1016/j.cis.2003.10.026.
Sutoo , D ., Akiyama , K ,. (2000). Chronic caffeine intake decreases brain serotonin levels in rats. Brain Res.;858(1):71-76. doi:10.1016/S0006-8993(99)02480-2.
Wong , HL ,. Bendayan , R ,.  Rauth , AM ,. Li , Y,. et al . (2007). Chemotherapy with drugs in solid lipid nanoparticles. Adv Drug Deliv Rev. 59(6):491-504. doi:10.1016/j.addr.2007.04.008.
 
 
Journal of Veterinary Laboratory Research
Volume 17, Issue 2 - Serial Number 28
In Progress
October 2025
Pages 213-221

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