Protective Effect of Liv.52 on Alcohol-Induced Fetotoxicity
Gopumadhavan, S., Jagadeesh, S., Chauhan, B.L. and Kulkarni, R.D., R&D Center, The Himalaya Drug Company, Bangalore, India.
Table 1: Maternal and fetal parameters following exposure to 20% v/v alcohol in water-feeding bottles during gestation period |
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Group dose |
Rx water (n=5) 10 ml/kg |
Rx alcohol (n=10) 20% v/v alcohol ad libitum ± 10 ml/kg water |
Rx alcohol + Liv.52 (n=9) 20% v/v alcohol ad libitum + Liv.52 3 g/kg with 10 ml/kg water as vehicle |
ANOVA |
Alcohol consumed (g/kg/day) |
— |
12.53 ± 0.42 |
11.82 ± 0.46 |
NS |
Maternal body weight gain (g) |
68.80 ± 8.69 |
47.30 ± 4.46 |
62.55 ± 4.06 |
p<0.038* |
Gestational food intake (g/rat/day) |
16.80 ± 0.81 |
14.70 ± 0.55 |
15.66 ± 0.38 |
NS |
No. of live fetuses |
10.40 ± 0.22 |
08.70 ± 0.82 |
10.44 ± 0.42 |
NS |
Mean litter weight (g) |
02.25 ± 0.08 |
02.02 ± 0.05 |
02.23 ± 0.05 |
p<0.030 |
Mean resorptions |
00.20 ± 0.18 |
02.50 ± 0.70 |
01.11 ± 0.11 |
p<0.030 |
Acetaldehyde level in amniotic fluid (µg/ml) |
— |
0.727 ± 0.046 |
0.244 ± 0.027 |
p<0.0001 |
Values are mean ± SE. Rx, treatment; ANOVA, one-way analysis of variance; NS, not significant. * RX water vs. RX alcohol (p<0.050); RX water vs. RX alcohol + Liv.52 (NS); RX alcohol vs. RX alcohol + Liv.52 (p<0.015). RX water vs. RX alcohol (p<0.022); RX water vs. RX alcohol + Liv.52 (NS); RX alcohol vs. RX alcohol + Liv.52 (p<0.013). RX water vs. RX alcohol (p<0.006); RX water vs. RX alcohol + Liv.52 (p<0.003); RX alcohol vs. RX alcohol + Liv.52 (p<0.050). RX water vs. RX alcohol + Liv.52 (p<0.0001). |
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DISCUSSION
It is known from previous studies that embryos exposed to acetaldehyde sustain fetal damage5. The mechanism of this deleterious effect of acetaldehyde is not certain, but acetaldehyde has been shown in other cell systems to form adducts with amino acids14 and to impair mitochondrial and other cellular transport functions15. More specifically, Priscott and Ford16 have studied the effects of acetaldehyde in vitro by incubating fetuses with and without placenta in a medium containing acetaldehyde. They demonstrated that the placenta can remove significant amounts of acetaldehyde from the medium and propose that placenta may be acting as an effective barrier to protect the fetus from the deleterious effects of acetaldehyde in maternal blood16. But as mentioned previously, Priscott has demonstrated direct toxic effects of acetaldehyde on fetuses in the in vitro system when acetaldehyde concentration in the amniotic fluid was 0.727 µg/ml (16.77 µM), which is far below the toxic concentration demonstrated by Priscott. The discrepancy may be due to the fact that Priscott incubated the embryos in he medium containing acetaldehyde for only 48 hr from Day 10 to Day 12, whereas in our experiments the dams were fed ethanol from Day 1 of pregnancy through Day 20 and the period of greatest sensitivity to acetaldehyde may occur at a time in development outside the range of Priscott’s exposure period. Acetaldehyde reaching the fetus through the blood supply may be more toxic and the placental barrier function in early pregnancy may not be adequate; also one does not know the acetaldehyde concentration inside the fetus in Priscott’s experiments. Further, blood acetaldehyde concentration in the mother may be higher than the amniotic fluid concentration. Unfortunately we did not measure maternal blood acetaldehyde concentrations.
In this study we observed significant deleterious effects on the fetus due to alcohol ingestion by the mother during gestation. Treatment with Liv.52 simultaneously prevented these deleterious effects on maternal gestational weight gain, the total number of live fetuses and mean litter weight (Fig.1). The mean resorptions in the Liv.52-treated group, although less than in the alcohol alone group, were nevertheless significantly more than in the control group (Fig. 2). It is also seen that the mean amniotic acetaldehyde level in the Liv.52-treated group was significantly lower than in the alcohol alone group (Fig. 3). It is, therefore, likely that the rapid acetaldehyde elimination action of Liv.52 may have caused reduction in maternal blood acetaldehyde levels8,17. This could have resulted in lesser exposure of fetuses to acetaldehyde and been responsible for the beneficial effects of Liv.52 administration. Only one dose of Liv.52 was used in this study. The possibility of Liv.52 preventing the binding of acetaldehyde to fetal tissue cannot be excluded. More definitive studies will have to be undertaken regarding acetaldehyde binding to fetal tissue and dose response of Liv.52 in preventing deleterious effects of acetaldehyde, as also simultaneous study of the effect of Liv.52 on maternal ethanol and acetaldehyde metabolism.
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Refference: http://www.himalayahealthcare.com/pdf_files/liv194.pdf
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