Effect of simultaneous prenatal exposure to ochratoxin a and citr1nin in the rat

Abstract

Ochratoxin A (OA) and citrinin (CT) are food-borne mycotoxins produced by several fungal species of the genera Aspergillus and Penicillium. Both are teratogenic in the rat. To determine the prenatal effects of simultaneous exposure to these toxins, pregnant Sprague-Dawley rats were injected either with a single individual subthreshold teratogenic dose of OA (1 mg/kg) or CT (30 mg/kg) or with both toxins. Toxins were dissolved in 5% sodium bicarbonate and administered subcutaneously on one of gestation d 5, 6, 7, 8, 10, 11, or 14. Maternal body weight gain of animals in the combination group was similar to other treatment groups and the control. Approximately 22-40% mortality in dams occurred on gestation d 5, 6, 7, and 14. Other than d 7, there was no significant effect on the number of implants. Treatment on d 5 or 7 resulted in increased fetal resorptions. Fetal body weights were not decreased significantly. OA and CT in combination resulted in a significant increase in gross malformations on d 6 and 7, visceral anomalies on d 5, 7, 8, and 10, and skeletal defects on d 5, 6, 7, 8, 10, and 14. When administered individually, OA and CT resulted in very few fetal resorptions. Fetal body weights were not significantly different except on d 8 of gestation following CT treatment. Individual toxin treatment resulted in minimal malformations on all gestation days. These results suggest that OA and CT, when administered concurrently, may interact to enhance prenatal toxicity and teratogenicity, and these results have focussed attention on the public health hazards of contamination of food with these mycotoxins.

Citrinin and endosulfan induced maternal toxicity in pregnant Wistar rats: pathomorphological study

“…The litter data showed 12.50% resorptions and 13.39% post implantation losses in the CIT group which was in agreement with the earlier findings in rats (Reddy et al, 1982;Mayura et al, 1984). These workers reported resorptions at a dose rate of 36 mg kg −1 b.w.…”

Hepatotoxic effect of ochratoxin A and citrinin, alone and in combination, and protective effect of vitamin E: In vitro study in HepG2 cell

“…In our combinatorial toxicity study we reduced the concentration to similar percentile values of the respective individual IC 50 values and obtained best results at 20% of the respective IC 50 values. Quite a few previous studies also reported synergistic/additive/antagonistic interaction between OTA and CTN in different models and for different end points (Summarized by F€ ollmann et al, 2014;Also, Siraj et al, 1981;Vesela et al, 1983;Mayura et al, 1984;Manning et al, 1985;Brown et al, 1986;Аnninou et al, 2014). But in nature mycotoxins can co-occur in any ratio (Bosulimi et al, 2008a), and the effect of mixtures is often dependent on the concentrations wherein an effect can change from additive to synergistic with increasing concentrations (F€ ollmann et al, 2014).…”

Ochratoxin A: The Continuing Enigma

“…to cause multiple teratogenic effects in developing rat embryos without coincident deleterious effects in the dams. 188 Thus, it appears that the teratogenic effects mediated by OTA are caused by a direct action of the parent compound on the developing fetus. The observations of Arora and coworkers 189 seem to corroborate these observations, as simultaneous administration of diethylstilbestrol and zearalenone, both of which have been shown to reduce transplacental blood flow, resulted in an overall reduction or absence of abnormal fetuses in rats exposed to OTA.…”