Biology Reference
In-Depth Information
4.1
Introduction
Maternal alcohol consumption during pregnancy may give rise to a set of serious
childhood health problems known as fetal alcohol syndrome (Eustace et al. 2003 )
and to alcohol-related birth defects (Warren and Bast 1988 ) , among them growth
retardation, structural brain abnormalities, behavioral and cognitive problems, and
learning difficulties (Chudley et al. 2005 ). In rodents (Ikonomidou et al. 2000 ;
Dikranian et al. 2005 ) and nonhuman primates (Farber et al. 2010 ) in vivo and in
humans in vitro (Hao et al. 2003 ) alcohol induces massive death of neurons in the
developing brain by apoptosis, a kind of cell death (Hotchkiss et al. 2009 ) , this pos-
sibly accounting for the morphological and functional disorders in children prena-
tally exposed to alcohol. Prevention of ethanol-induced apoptosis can save many
neurons and significantly reduce sequences of alcohol intoxication. Among possible
drugs for apoptosis prevention taurine seems particularly attractive, since it is a
compound naturally present in abundance in the nervous system (Huxtable 1992 ;
Sturman 1993 ), involved in apoptosis regulation (Takatani et al. 2004 ; Wu et al.
2009 ) and protective to many types of cells under different pathological conditions
(Ulrich-Merzenich et al. 2007 ; Taranukhin et al. 2008 ; Das et al. 2009 ; Zhang et al.
2010 ). We have previously shown that taurine at a dose of 2 g/kg saves about 50%
of dying neurons from ethanol-induced apoptosis in the internal (Taranukhin et al.
2010 ) and external (Taranukhin et al. 2012 ) layers of the developing cerebellum of
7-day-old mice. However, a further increase in taurine doses with an eye to protect-
ing more neurons becomes dangerous for the whole organism and may even kill
treated animals. In the present work we describe the new phenomenon of combined
toxicity of taurine and ethanol and seek to establish its possible mechanisms.
4.2
Materials and Methods
4.2.1
Animals and Experimental Protocols
Adult NMRI mice for experiments and breeding were purchased from Harlan, the
Netherlands. In the experiments male and female mice of three age groups, 7 days old (day
of birth is day 0), adult (5 to 6 months old), and old (12 to 13 months old), were used.
The mice were divided into four experimental groups: control, ethanol treated,
taurine treated, and ethanol+taurine treated. Ethanol (20% w/v solution diluted in
saline) and taurine (7% w/v solution diluted in saline) were administered subcutane-
ously to 7-day-old mice and intraperitoneally to adult and old mice. The different
doses of ethanol tested ranged from 0 to 12 g/kg and of taurine from 0 to 12 g/kg
together with their combinations, the objective being to find a minimal 100% lethal
dose at each age. Taurine and ethanol were injected in two half-doses: taurine at 0
and 4 h, and ethanol at 1 and 3 h. The control animals were given saline injections
equal to those given to the ethanol+taurine-treated group. The animals were moni-
tored for 14 days to detect any signs of toxicity or lethality.
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