Adverse placental effect of formic acid on hCG secretion is mitigated by folic acid.

AIMS: Formic acid has recently been detected in maternal blood and umbilical cord blood of infants born to alcohol abusing mothers. This toxic metabolite of methanol requires folate for detoxification. We hypothesized that formic acid produced in the maternal circulation will transfer across the placenta and will be toxic to the placenta. Our objectives were, first, to determine whether formic acid transfers across the human placenta and whether it is toxic to the placenta and second, to determine whether folate can decrease transplacental transfer of formic acid and mitigate toxicity. METHODS: Dual perfusion of a single placental lobule ex vivo was used to characterize the transfer of formic acid across the placenta. After a 1-h control period, formic acid (2 mM) was introduced into the maternal circulation with (n = 4) or without folate (1 µM) (n = 4) and was allowed to equilibrate for 3 h. RESULTS: Formic acid transferred rapidly from the maternal to the fetal circulation, and transfer was not altered with the addition of folate. Compared with the control period, there was a significant decrease in hCG secretion (P = 0.03) after addition of formic acid. The addition of folic acid to the perfusate mitigated the decrease in hCG. CONCLUSIONS: Formic acid rapidly transfers across the placenta and thus has the potential to be toxic to the developing fetus. Formic acid decreases hCG secretion in the placenta, which may alter steroidogenesis and differentiation of the cytotrophoblasts, and this adverse effect can be mitigated by folate.

Prevention of hepatotoxic responses to chemicals by glycyrrhizin in rats.

To clarify whether glycyrrhizin, the aqueous extract of licorice root and a drug for treatment of chronic active hepatitis, prevents the development of hepatic injury induced by carbon tetrachloride, allyl formate, and endotoxin, the present study was undertaken in rats. The treatment with glycyrrhizin 20 hr before carbon tetrachloride administration protected the development of the pericentral hepatocellular necrosis. Glycyrrhizin treatment 2 hr prior to the administration of allyl formate also inhibited the development of the periportal hepatocellular necrosis. However, glycyrrhizin did not protect the development of endotoxin-induced focal and random hepatocellular necrosis. These experimental results suggest that glycyrrhizin has no protective effect on hepatic injury following sinusoidal circulatory disturbance as seen in the case of endotoxin and that glycyrrhizin can protect against hepatotoxicity induced by the direct action on the hepatocytes due to hepatotoxins, such as carbon tetrachloride and allyl formate.

Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity.

Application by pledget of the M1-antimuscarinic receptor agent pirenzepine (40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats inhibited the slope of the integrated phrenic response to CO2 by 32.5% (P less than 0.03) and the maximum value by 21.1% (P less than 0.01). Similar application of the imidazole-histidine blocking agent diethyl pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and the maximum value by 29.3% (P less than 0.05). Both responses confirm previous results. DEPC treatment decreased the effectiveness of subsequent pirenzepine application such that although slope and maximum were further decreased, the values were not significantly different from those after DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory effect. The results raise the possibility that the inhibitory effects of DEPC on CO2 chemosensitivity are via muscarinic receptors and that muscarinic receptor involvement in CO2 chemosensitivity requires the presence of imidazole-histidine. Analysis by scintillation counting of successive 100-micron sections of medulla after rostral area application of [3H]pirenzepine indicated that the pirenzepine and DEPC effects are most probably within 2.0 mm of the ventral surface as measured from the midline, well away from the dorsal and ventral respiratory group neurons.

[Effect of 2,4-diamino-5-chlorphenyl-6-ethylpyrimidine on the oncorporation of P32-phosphate into adenylic nucleotides of rat embryo and placenta]. / Vliianie 2,4-diamino-5-khlorfenil-6-etilpirimidina na vkliuchenie P32-fosfata v adenilovye nukleotidy embrionov i platsenty krys

Teratogenic doses of antimalaria preparation, 2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine (chloridine), known in biochemistry as a specific inhibitor of dihydrofolate reductase, result in the decrease of 32P-phosphate incorporation into ATP and ADP, coupled with the inhibitions of DNA synthesis, in rat embryo and placenta on 13th day of development, while the incorporation of 14C-formiate into free nucleotides of acid soluble embryo and placenta fractions (at the same intervals after teratogen injections), is the same as in the control. These data show that the primary blocking of folate cycle and DNA biosynthesis in 13 days old embryos with induced anomalies of development is some way coupled with disturbances of ATP metabolism.

Effect of cannabinoids on the abdominal constriction response in mice: within cannabinoid interactions.

After oral administration to mice, delta9-tetrahydrocannabinol (THC) and cannabinol (CBN) caused a dose-dependent suppression of the abdominal constriction response to formic acid. Cannabinol was 50 times less active than THC and cannabidiol (CBD) was without effect. The effects of THC and CBN were additive. CBD antagonised the antinociceptive effects of both THC and CBN in a dose-dependent manner.