Coccinin

Cerebral cholinergic muscarinic receptors (MR) have been suggested as one of the sensitive biochemical endpoints of the central nervous system altered by developmental exposure to the widespread seafood contaminant methylmercury (MeHg). In adult rats, MeHg has been shown to alter MR binding both in the brain and lymphocytes, supporting the use of MR in blood cells as a surrogate marker of CNS changes. The effects of MeHg have been evaluated on rat lymphocyte MR binding (using [3H]QNB as specific muscarinic ligand) in vivo (after perinatal exposure) and in vitro. For comparison, in vitro studies were also performed on human lymphocytes. Exposure to 1 mg MeHg/kg/day during pregnancy and lactation (from GD7 to PND7) significantly enhanced lymphocyte MR density in both adult and young rats 21 days after delivery, with a more pronounced effect in the mothers (B(max) increase of 139%) than in the male offspring (+49%) and female offspring (+73%) as compared with their respective controls (33+/-4, 41+/-8, and 37+/-4 fmol/million cells), in accordance with the higher Hg levels detected in the adult blood (11.3+/-2.2 microg/mL) than in pups (1.3+/-0.4 microg/L in both genders). A lower MeHg dose (0.5 mg/kg/day) was without any effect on lymphocyte MRs. In in vitro studies, MeHg was an almost equipotent inhibitor of (3)H-QNB binding to rat and human lymphocyte MRs (IC50 values were 4.1+/-0.29, 5.2+/-0.51, and 5.0+/-0.9 microM for total rat lymphocytes, rat T lymphocytes, and total human lymphocytes, respectively). Notably, the IC50 values for MeHg to lymphocyte MRs were comparable to the Hg levels reached in blood (5-50 microM) of the PND21 rats exposed to MeHg. The finding that the MR binding is a target for the effects of MeHg in peripheral blood cells is in accordance with our previous data in brain [Coccini et al., 2006. Effects of developmental co-exposure to methylmercury and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) on cholinergic muscarinic receptors in rat brain. Neurotoxicology, in press], and supports the use of this peripheral endpoint as a biomarker of MeHg-induced cerebral muscarinic alterations. The similarity of MeHg IC50 binding data between human and rat in peripheral tissues suggests the possible application of such biomarker to humans exposed to environmental chemicals.

Mycotoxin enniatin B (ENN B) is a secondary metabolism product by Fusarium fungi. It is a well-known antibacterial, antihelmintic, antifungal, herbicidal, and insecticidal compound. It has been found as a contaminant in several food commodities, particularly in cereal grains, co-occurring also with other mycotoxins. The primary mechanism of action of ENN B is mainly due to its ionophoric characteristics, but the exact mechanism is still unclear. In the last two decades, it has been a topic of great interest since its potent mammalian cytotoxic activity was demonstrated in several mammalian cell lines. Moreover, the co-exposure in vitro with other mycotoxins enhances its toxic potential through synergic effects, depending on the concentrations tested. Despite its clear cytotoxic effect, European Food Safety Authority stated that acute exposure to ENNs, such as ENN B, does not indicate concern for human health, but a concern might be the chronic exposure. However, given the lack of relevant toxicity data, no firm conclusion could be drawn and a risk assessment was not possible. In fact, very few studies have been carried out in vivo and, in these studies, no adverse effects were observed. So, research on toxicological effects induced by ENN B is still on-going. Recently, some studies are dealing with new advances regarding ENN B. This review summarizes the information on biochemical and biological activity of ENN B, focusing on toxicological aspects and on the latest advances in research on ENN B.