Chronic allopurinol treatment during the last trimester of pregnancy in sows: effects on low and normal birth weight offspring.
Low-birth-weight (LBW) children are born with several risk factors for disease, morbidity and neonatal mortality, even if carried to term. Placental insufficiency leading to hypoxemia and reduced nutritional supply is the main cause for LBW. Brain damage and poor neurological outcome can be the consequence. LBW after being carried to term gives better chances for survival, but these children are still at risk for poor health and the development of cognitive impairments. Preventive therapies are not yet available. We studied the risk/efficacy of chronic prenatal treatment with the anti-oxidative drug allopurinol, as putative preventive treatment in piglets. LBW piglets served as a natural model for LBW. A cognitive holeboard test was applied to study the learning and memory abilities of these allopurinol treated piglets after weaning. Preliminary analysis of the plasma concentrations in sows and their piglets suggested that a daily dose of 15 mg.kg(-1) resulted in effective plasma concentration of allopurinol in piglets. No adverse effects of chronic allopurinol treatment were found on farrowing, birth weight, open field behavior, learning abilities, relative brain, hippocampus and spleen weights. LBW piglets showed increased anxiety levels in an open field test, but cognitive performance was not affected by allopurinol treatment. LBW animals treated with allopurinol showed the largest postnatal compensatory body weight gain. In contrast to a previous study, no differences in learning abilities were found between LBW and normal-birth-weight piglets. This discrepancy might be attributable to experimental differences. Our results indicate that chronic prenatal allopurinol treatment during the third trimester of pregnancy is safe, as no adverse side effects were observed. Compensatory weight gain of treated piglets is a positive indication for the chronic prenatal use of allopurinol in these animals. Further studies are needed to assess the possible preventive effects of allopurinol on brain functions in LBW piglets.
Emotion & Cognition Group, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Elise T
ET
Gieling
Emotion & Cognition Group, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands ; Brain Center Rudolf Magnus, Utrecht University, Utrecht, The Netherlands.
Alexandra
A
Antonides
Veterinary Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Johanna
J
Fink-Gremmels
Adaptation Physiology Group of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Kim
K
Ter Haar
Pig Health Unit, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Wikke I
WI
Kuller
Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Ellen
E
Meijer
Emotion & Cognition Group, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands ; Brain Center Rudolf Magnus, Utrecht University, Utrecht, The Netherlands.
Rebecca E
RE
Nordquist
Pig Health Unit, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands.
Jacomijn M
JM
Stouten
Emotion & Cognition Group, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands ; Brain Center Rudolf Magnus, Utrecht University, Utrecht, The Netherlands.
Elly
E
Zeinstra
Emotion & Cognition Group, Department of Farm Animal Health, Faculty of Veterinary Medicine, University Utrecht, Utrecht, The Netherlands ; Brain Center Rudolf Magnus, Utrecht University, Utrecht, The Netherlands.
Franz Josef
FJ
van der Staay
D000493:Allopurinol / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects*; D001784:Blood Gas Analysis; D005260:Female; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000187:drug effects*; D013552:Swine
D000975:Antioxidants; D018696:Neuroprotective Agents; D000493:Allopurinol