Embryo-Fetal Development Studies with The Dietary Supplement Vinpocetine in The Rat and Rabbit

Natasha Catlin, Suramya Waidyanatha, Eve Mylchreest, Lutfiya Miller-Pinsler, Helen Cunny, Paul Foster, Vicki Sutherland, Barry McIntyre
Birth Defects Research (2018) DOI: https://doi.org/10.1002/bdr2.1207 PMID: 29460393

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Abstract

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine.

Figures

Figure 1. Rat maternal body weight throughout gestation.

Figure 1 (62 KB)

Figure 2. Rabbit maternal body weight throughout gestation.

Figure 2 (83 KB)

Figure 3. Mean concentration of vinpocetine (A) and apovincaminic acid (B).

Mean concentration of vinpocetine (A) and apovincaminic acid (B) in pregnant rabbit plasma 1 and 2 hr following oral vinpocetine administration.

Figure 3 (46 KB)

Figure 4. Comparison of dose-normalized plasma concentrations.

Comparison of dose-normalized plasma concentrations of vinpocetine (A) and apovincaminic acid (B) in pregnant rats and rabbits at 1 and 2 hr following oral vinpocetine administration. Pregnant rat plasma samples were processed and analyzed as detailed in previously published toxicokinetics studies of vinpocetine and apovincaminic acid (Waidyanatha, 2017). The present previously published data for the rat are being presented here for direct comparison purposes to the presently reported rabbit data.

Figure 4 (43 KB)

Tables

Table 1. Dam body weight gain and food consumption.

Table 1 (112 KB)

Table 2. Dam Cesarean section observations and fetal weights.

Table 2 (116 KB)

Table 3. Rat visceral findings.

Table 3 (76 KB)

Table 4. Rat skeletal findings.

Table 4 (153 KB)

Table 5. Doe body weight gain and food consumption.

Table 5 (82 KB)

Table 6. Doe Cesarean section observations and fetal weights.

Table 6 (131 KB)