X-Message-Number: 27621
Date: Wed, 15 Feb 2006 20:31:13 -0800 (PST)
From: Doug Skrecky <>
Subject: nicotine for vitrification solutions?

[Complete block of ethanol effects was achieved by the highest
dose of nicotine (20 microM).]

Neurotox Res. 2005;7(4):319-22.
Nicotine blocks ethanol-induced apoptosis in primary cultures of
rat cerebral cortical and cerebellar granule cells.
  Nicotine's counteraction of adverse effects of ethanol on
cognitive function and motor coordination may play a major role in
the observed high incidence of smoking among alcoholics. Previously,
we have observed protective effects of nicotine against
ethanol-induced neurotoxicity in cultured cortical and cerebellar
granule cells as determined by lactate dehydrogenase assay.
Ethanol-induced apoptosis may be a contributory mechanism to its
neuronal toxicity. In this study we sought to determine whether
ethanol induces formation of caspase 3 (reflective of apoptosis) in
these cells and whether these effects may be blocked by nicotine
pretreatment. Primary cultures of cerebral cortical and cerebellar
granule cells were prepared from the brains of 20 day old
Sprague-Dawley fetuses. Exposure of cells to ethanol (10-100 mM)
for 3 days resulted in a dose-dependent increase in caspase 3
activity and cytotoxicity. Pretreatment with nicotine (5-20 microM)
dose dependently attenuated these effects of ethanol. Complete block
of ethanol effects was achieved by the highest dose of nicotine
(20 microM). Nicotine, at concentrations administered, did not
affect caspase activity or neuronal viability. These results suggest
that at least some of the neurotoxic effects of ethanol may be
mediated by apoptosis and that pretreatment with nicotine can prevent
these effects of ethanol. Anti-apoptotic effects of nicotine in this
model may be suggestive of potential use of nicotinic agonists in
neurotoxic insults and/or neurodegenerative disorders.

Neurotox Res. 2004;6(4):311-6.
Nicotine inhibits ethanol-induced toxicity in cultured cerebral
cortical cells.
  The high incidence of smoking among alcoholics may be partially
due to nicotine's ability to counteract some of the adverse
effects of ethanol on motor coordination and/or cognitive
functions. Neuroprotective effects of nicotine on ethanol-induced
toxicity in cerebellar granular cells have been observed. In this
study, we sought to determine whether similar protection is
observed in neocortical cells and if so, what specific nicotinic
receptor subtypes may be mediating the actions of nicotine.
Primary cultures of neocortical cells were prepared from 20-day
embryos obtained from time-pregnant Sprague-Dawley rats. Cells
were cultured for 10 days and were then exposed for 3 days to
various concentrations of ethanol with and without pretreatment
with nicotine and nicotinic antagonists. Cellular toxicity was
evaluated by measuring the lactate dehydrogenase level.
Administration of ethanol (10-100 mM) resulted in a dose-dependent
toxicity. Pretreatment with nicotine 5-20 microM resulted in a
dose-dependent protection against ethanol-induced toxicity. The
effects of nicotine were blocked by pretreatment with nicotinic
antagonists such as mecamylamine (1-20 microM),
dihydro-beta-erythroidine (DHBE) 50 nM-1.0 microM and
methyllycaconitine (MLA) 5 nM-1 microM in a dose-dependent manner.
Compared to previous studies, higher ethanol concentrations were
required to induce toxicity in neocortical vs cerebellar granule
cells. Moreover, the effects of nicotine in the neocortical cells
were blocked by lower concentrations of MLA, but higher
concentrations of DHBE compared to cerebellar cells. Collectively,
the results suggest differential sensitivity of various neuronal
populations to the toxic effect of ethanol. Furthermore,
protective effects of nicotine against alcohol in various regions
appear to be mediated by different nicotinic receptor subtypes.
The neuroprotective effect of nicotine against ethanol-induced
toxicity may be a contributing factor to the high incidence of
smoking among alcoholics.

Alcohol Clin Exp Res. 2000 Oct;24(10):1583-92.
Chronic, but not acute, nicotine exposure attenuates ethanol
withdrawal-induced hippocampal damage in vitro.
  BACKGROUND: Long-term ethanol use and long-term tobacco use
frequently occur together, which suggests concurrent dependence
on ethanol and nicotine. Consequences of this form of polydrug
dependence are not well understood, however. Previous evidence
suggests detrimental effects of long-term ethanol and beneficial
effects of nicotine exposure on neuronal viability. Thus, the
present study was designed to use an organotypic hippocampal slice
culture model to examine the ability of chronic and acute nicotine
exposure to reduce neurotoxicity associated with withdrawal from
long-term ethanol exposure. METHODS AND RESULTS: Twenty-four hours
of withdrawal after continuous 10 day ethanol exposure (50 or
100 mM in culture medium) resulted in cytotoxicity in hippocampal
slice explants obtained from neonatal rat, most notably in pyramidal
cell layers of the CA1 region. Exposure of slices to the
N-methyl-D-aspartate receptor blocker MK-801 during ethanol
withdrawal significantly reduced this toxicity. Exposure of slices
to nicotine (0.1-10.0 microM) during the 24 hr withdrawal period
did not reduce hippocampal damage. However, treatment of slices
with nicotine (0.1-10.0 microM) during 10 days of ethanol exposure
was associated with significant reductions in subsequent
withdrawal-induced cytotoxicity, an effect reduced by mecamylamine
coexposure with nicotine and ethanol. CONCLUSIONS: These findings
indicate the development of marked hippocampal neurotoxicity during
withdrawal from long-term ethanol exposure that is mediated, in
part, by overactivation of N-methyl-D-aspartate receptors.
Furthermore, these data suggest that one consequence of concurrent
dependence on ethanol and nicotine may be reduced neurological
damage associated with ethanol withdrawal.

Dig Dis Sci. 1990 Jan;35(1):106-12.
The influence of acute or chronic nicotine treatment on
ethanol-induced gastric mucosal damage in rats.
  The influences of acute or chronic nicotine pretreatment on
ethanol-induced changes on gastric secretion, mucosal blood flow
(GMBF), and glandular mucosal damage were studied in anesthetized
rats. Ethanol administration decreased gastric acid secretion and
GMBF, which were accompanied by a marked increase in gastric mucosal
damage. Acute nicotine incubation 2 or 4 mg dose-dependently elevated
both the titratable acid in the luminal solution and the gastric
secretory volume; it also prevented the depressive action on GMBF
and gastric mucosal damage in ethanol-treated animals. Chronic
nicotine treatment for 10 days reduced the inhibitory action of
ethanol on gastric acid secretion; the higher dose (25 micrograms/ml
drinking water) potentiated the decrease of GMBF and the ulcerogenic
property of ethanol. However, chronic treatment with the lower dose
(5 micrograms/ml drinking water) had the opposite effects; it also
markedly increased the gastric secretory volume. It is concluded that
acute nicotine pretreatment elevates, whereas chronic nicotine
pretreatment differentially affects GMBF. These effects could account
for their protective or preventive actions on ethanol ulceration. The
increase in nonacid gastric secretory volume by nicotine could
partially explain its antiulcer effect. Furthermore, the acid
secretory state of the stomach appears unrelated to the ulcerogenic
property of ethanol.

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