title: High dose of caffeine administered to pregnant rats causes histopathological changes in the cornea of newborn pups.
abstract: BACKGROUND
  Caffeine is frequently used during pregnancy and associated with teratogenic effects, such as low birth weight, hearth and digital defects, cleft palate and abortion with fetal loss. This study investigated histopathologically the effects of caffeine on neonatal rat cornea.
  
  
  METHODS
  Fifty pregnant Wistar-Albino rats (dams) were randomly divided into five groups, one control and four experimental. Between day 9 and 21 of gestation, group 1 dams (control, n=10) were exposed to intraperitoneal (i.p.) SF daily until delivery. Group 2 (n=10), group 3 (n=10) and group 4 (n=10) dams were treated with i.p. caffeine at doses of 25, 50 and 100 mg/kg/d, respectively, for the same period. Group 5 dams were given caffeine in distilled water in a gavage at a dose of 50 mg/kg/d during the same period. After normal delivery, the litters were killed at postnatal day 1 or 30 and the eyes were enucleated for corneal histopathologic investigation.
  
  
  RESULTS
  Control and group 1 eyes had normal corneal epithelium, regular stromal fibers, descement membrane and monolayer inner corneal endothelium. The remaining experimental litters demonstrated changes, such as vacuolated endothelial cells with proliferation, hyperchromasia, polymorphism, endothelial cell agenesis, increased stromal mitotic activity and focal increase in corneal thickness with widely separated corneal lamellae in the injured area. These changes occurred most often in the litters treated with high doses of caffeine.
  
  
  CONCLUSIONS
  Excessive gestational caffeine intake has been shown histopathologically to have some teratogenic effects on newborn rat cornea.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Erciyes University, Kayseri, Turkey. evereklioglu@hotmail.com
authors.forename: Cem
authors.initials: C
authors.lastname: Evereklioglu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Sari
authors.forename: Belgin
authors.initials: B
authors.lastname: Alasehirli
authors.forename: Emin
authors.initials: E
authors.lastname: Güldür
authors.forename: Beyhan
authors.initials: B
authors.lastname: Cengiz
authors.forename: Zcan
authors.initials: Z
authors.lastname: Balat
authors.forename: Cahit
authors.initials: C
authors.lastname: Bagci
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000008:administration & dosage / Q000633:toxicity*; D003315:Cornea / Q000002:abnormalities* / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004728:Endothelium, Corneal / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D019573:Epithelium, Corneal / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D005260:Female; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002110:Caffeine