Lethality of Taurine and Alcohol Coadministration in Mice - Advances in Experimental Medicine and Biology - page 33

in cell protection against alcohol-induced apoptosis. However, contrary to our
expectations taurine at a dose of 4 g/kg co-administered with 5 g/kg ethanol killed
about 60% of treated mice and 6 g/kg combined with 5 g/kg ethanol 100%. Interestingly,
6 g/kg taurine and 5 g/kg ethanol alone were safe for the animals. It would thus appear
that taurine potentiates the adverse effects of ethanol.
It is well known that ethanol at high doses can induce death, but little is known
of taurine toxicity or of the combination of taurine with ethanol or other drugs. In
experiments on dogs taurine at a single intravenous dose of 2 g/kg has proved safe
for the animals and during a 14-day period of observation there were no dead ani-
mals or any signs of toxicity (Nishizawa et al. 1991 ). Experiments on Wistar rats
have shown that taurine in a single dose of 7 g/kg (intravenously) or 5 g/kg (orally)
has no toxic effect on the animals, which also survived for 14 days without any sign
of toxicity or abnormality upon autopsy (Kihara et al. 1991 ). All these studies show
that taurine is minimally toxic. We found only one study in which taurine at doses
of 7.5 and 6.0 g/kg involved 100 and 50% lethality, respectively, after a single sub-
cutaneous injection (Goldberg and Jefferies 1946 ). In our experiments taurine alone
administered at a dose of 6 g/kg was not toxic to the animals, possibly because we
injected it in two half-doses 4 h apart. When the animals received first only 3 g/kg
taurine and after 4 h again 3 g/kg, taurine from the first injection was partly incor-
porated into the bile or secreted into the urine, as shown by the decrease in taurine
levels in the blood (Lallemand and De Witte 2004 ; Taranukhin et al. 2010 ) .
To test the hypothesis that the lethality of combined taurine and ethanol not only
pertains for developing 7-day-old mice, which at this age are highly sensitive to
ethanol toxicity (Ikonomidou et al. 2000 ), we repeated our experiments on adult
(5 to 6 months old) and old (12 to 13 months old) mice. We thus established the
maximal doses of ethanol for adult (8 g/kg) and old (6 g/kg) mice which do not
induce mortality. Our present data (8 g/kg) differ slightly from the results of some
other authors (Schechter and Meehan 1995 ) with regard to the ethanol dose which
does not induce death in young adult mice (6 g/kg), probably by reason of differ-
ences in ethanol sensitivity between the two strains of mice tested. Our data on dif-
ferences in the toxicity of different doses of ethanol in adult and old mice are similar
to those obtained on rats, in which the 50% lethal dose for 3-4-month-old rats was
significantly higher than that for 10-12-month-old rats (Wiberg et al. 1970 ) . In adult
and old mice the combined toxicity of taurine and ethanol sufficient to induce 100%
mortality was significantly higher than in 7-day-old mice. Sensitivity to the com-
bined toxicity of taurine and ethanol is thus age dependent.
Taurine treatment significantly attenuates the stress-induced elevation in blood
glucose in rats (Nakagawa and Kuriyama 1975 ). Taurine exerts a hypoglycemic
action in glucose supplementation-induced hyperglycemia (Kulakowski and Maturo
1984 ; Kaplan et al. 2004 ). These findings on the ability of taurine to reduce blood
glucose and the observation that ethanol can also lower it (Huang and Sjöholm
2008 ) allow us to assume that the lethality of taurine and ethanol coadministration
can be induced by hypoglycemia. Blood glucose after taurine and ethanol coadmin-
istration was significantly decreased in adult and old mice. In adult mice the decrease
in glucose concentration was still far from the dangerous level. The old mice could