Reproductive Toxicology 65 (2016) 359–364
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Reproductive Toxicology
j ourna l h o mepa ge: www.elsevier.com/locate/reprotox
Evaluation of the protective effect of thiamine pyrophosphate based
on the biochemical analysis of rabbit foetuses at 30 days of gestation
M.A. Jiménez-Bravo
a,b
, D. Mota-Rojas
c,∗
, H. Orozco-Gregorio
d
, B. Pérez-Guille
b
,
R. Soriano-Rosales
b
, P. Roldan-Santiago
c
, M. Alonso-Spilsbury
c
, E. Arch-Tirado
e
,
P. Mora-Medina
f
, J. Martínez-Burnes
g
a
Ph. D. Program in Biological Sciences and Health, Universidad Autónoma Metropolitana (UAM), Mexico City 04960, Mexico
b
Experimental Surgery Department, Instituto Nacional de Pediatría (INP), Mexico City 04530, Mexico
c
Stress Physiology and Farm Animal Welfare, Department of Animal Production and Agriculture, Universidad Autónoma Metropolitana (UAM), Mexico City
04960, Mexico
d
Facultad de Agronomía y Veterinaria, Universidad Autónoma de San Luis Potosí (UASLP), San Luis Potosí 78321, Mexico
e
Bioacoustics Laboratory, Instituto Nacional de Rehabilitación (INR), Mexico City 14389, Mexico
f
Department of Livestock Sciences, FESC., Universidad Nacional Autónoma de México (UNAM), State of Mexico 54714, Mexico
g
Postgraduate Division and Research, Veterinary Medicine Faculty, Universidad Autónoma de Tamaulipas, Ciudad Victoria, Tamaulipas, Mexico
a r t i c l e i n f o
Article history:
Received 4 November 2014
Received in revised form 3 September 2016
Accepted 9 September 2016
Available online 11 September 2016
Keywords:
Foetuses
Hypoxic-encephalopathy
Protective effect
Thiamine pyrophosphate
Foetal welfare
Cocarboxylase
a b s t r a c t
This study evaluated the effects of thiamine pyrophosphate (PPT) on the biochemical profiles of full-term
rabbit foetuses that were subjected to experimental ischemia followed by 24 h reperfusion. A total of 16
gestating rabbit dams were divided into two groups, one of which was treated by administering PPT and
subjected to a process ischemia. During this interval, fetal blood samples were drawn from each dam (in
the ischemia group) at 0, 15 and 45 min. Ischemia for 15 and 45 min was not associated with changes in
lactate levels of the Ischemia group foetuses. However, in the foetuses in the reperfusion groups without
PPT lactate levels were significantly higher after 15 and 45 min of arterial occlusion compared to time
zero. These results demonstrate that PTT alters some acute and some longer-term biochemical outcomes
of uterine ischemia perhaps important in preserving energy metabolism under hypoxic conditions.
© 2016 Elsevier Inc. All rights reserved.
1. Introduction
Disorders that damage the developing brain are a significant
cause of death or permanent disability, such as cerebral palsy.
Hypoxic-ischemia encephalopathy (HIE) occurs at a rate of about
three per thousand live-born, full-term infants [1]. While mild
forms of encephalopathy have good prognosis, in moderate and
severe cases the risk of death [2] or neurodevelopmental sequal
in the surviving offspring increases greatly [3]. Asphyxia events
have been evaluated in several animal models, including pigs [4,5],
guinea pigs [6], and rats [7]. In these animals, asphyxia triggers a
cascade of cellular biochemical events that lead to temporary alter-
ations in cellular function and/or cell death. Tissue hypoxia and
∗
Corresponding author at: Calzada del Hueso 1100, Col. Villa Quietud, 04960
Coyoacán, Mexico, D.F., Mexico.
E-mail addresses: dmota100@yahoo.com.mx, dmota@correo.xoc.uam.mx
(D. Mota-Rojas).
ischemia, meanwhile, can result in the depolarization of neuronal
membranes, alterations of cellular ion homeostasis, and changes
in energy metabolism [8]. Various alternative therapies have been
utilised to treat the secondary lesions that result from hypoxic
events, including hypothermia and the administration of free rad-
ical scavengers or calcium channel blockers [9]. Some of these
measures have been incorporated into clinical practice with rela-
tive success. However, considering that damage is progressive and
largely-dependant on the energy supplies that reach the cell, an
additional option could consist in administering molecules that
act on the enzymatic pathways associated with energy produc-
tion in order to reduce the extent of damage. Thiamine exerts its
metabolic action primarily through thiamine pyrophosphate, or
cocarboxylase (PPT), which acts through two different pathways;
first, by donating phosphate groups to form ATP and other energy
molecules, such as TATP (adenosine-thiamine-triphosphate); and,
second, as an indispensable co-factor in the activation of enzymes
involved in energy-generating processes through the Krebs Cycle or
the pentose cycle [10]. Although Valenzuela [7] has demonstrated
http://dx.doi.org/10.1016/j.reprotox.2016.09.003
0890-6238/© 2016 Elsevier Inc. All rights reserved.