Effect in rats of simultaneous prenatal exposure to ochratoxin A and aflatoxin B₁. I. Maternal toxicity and fetal malformations

Abstract

Ochratoxin A (OA) and Aflatoxin B1 (AFB1), the food borne mycotoxins are produced by several fungal species of the genera Aspergillus and Penicillium. To determine the teratogenic effects, these mycotoxins were administered orally either individually or in combination to the pregnant Wistar rats on days 6-15 of gestation. OA and AFB1 were dissolved in corn oil and different doses of OA (0.125, 0.25, 0.50, and 0.75 mg/kg), AFB1 (0.125, 0.25, 0.50, and 1.00 mg/kg), and a combination of OA+AFB1 (0.125+0.125; 0.25+0.50; 0.50+0.25 mg/kg) were given by gastric intubation to rats. During dosing period, the body weight and body weight gains significantly decreased at a higher dosage, in both individual and combined treatments. In all the combination treatments, the percent implants resorbed, fetal body weights, and crown-rump lengths were comparable to those of controls and with the individual mycotoxin treatment. The number of dead fetuses was significantly increased in the high OA combination (OA+AFB1 0.50+0.25) group as compared with the other two combinations. OA and AFB1 alone and in combination caused various gross, skeletal, and visceral anomalies. The occurrence was considerably less pronounced in fetuses of AFB1 and combination groups as compared with those of OA group fetuses. The exencephaly, incomplete closure of skull, wavy and fused ribs, agenesis of the ischium bone, and enlarged renal pelvis, recorded in OA treatment and ear abnormality and incomplete ossification of skull bones observed in AFB1 when given individually, were not seen in combination groups. However, new manifestations, such as gastroschisis and syndactyly were observed and the incidence of cardiac defects was increased in fetuses due to the combined treatment. The results of the present study indicated that there is some interaction between these mycotoxins that resulted in reduced teratogenic activity of OA in the presence of AFB1. Apparently, new manifestations observed in combination treatment points to the potential threat of teratogenicity in terms of public health hazards.

Effects of Aflatoxin B1 on the skeletal system of rabbit (Oryctolagus cuniculus) fetuses

“…The fetuses of treated dams in this work by a dose of 0.1 mg/kg AFB1 showed the commencement of the membranous ossification of the bones of the dorsal surface of skull and no cartilaginous template were formed between the bones of the ventral aspect of the skull while Wangikar et al (2004bWangikar et al ( , 2005 mentioned incomplete ossification of the skull bones in the same animal with same dose of AFB1 as well as El-Tahan (2013) in rat fetuses with the same dose.…”

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

“…In rats, AFB1 and OTA showed no interaction regarding the measurement of mortality, weight gain, or most serum biological parameters but the anaplastic and hyperchromatic nuclei, necrosis and bile duct proliferation observed were more pronounced in the combined toxin group after 4 months (Rati et al, 1981). In rats and rabbits, the combination resulted in less teratogenicity than OTA alone, although some new manifestations appeared (Wangikar et al, 2004;Wangikar et al, 2005). There was no data available regarding the combined genotoxicity in vivo, but in vitro, the combination showed genotoxic additive effects in Vero cells (green monkey kidney cells) (El Golli-Bennour et al, 2010).…”

Toxico-Pathological Effects of In Ovo Inoculation of Ochratoxin A (OTA) in Chick Embryos and Subsequently in Hatched Chicks

“…In experimental studies, residues of OTA have been detected in the blood and tissues (Denli et al 2008;Biro et al 2002;Niemiec et al 1994) and also in the eggs (Frye and Chu 1978;Fuchs et al 1988;Niemiec et al 1994) of birds kept on OTAcontaminated ration. Teratogenic and embryotoxic effects of OTA alone and in combination with other mycotoxins have been reported in rat, rabbit, and chicken (Wangikar et al 2007(Wangikar et al , 2005Wangikar, Dwivedi, and Sinha 2004;Wei and Sulik 1996;Vesala, Vesely, and Jelinek 1983;Gilani, Bancroft, and Reily 1978). A significant decrease in the number of immunoglobulin bearing cells in spleen and bursa of Fabricius and also poor production performance of the progeny of breeder hens maintained on OTA-contaminated ration have been reported by Zahoor-ul-Hassan et al (2011) andSemeniuk et al (1971).…”