Morphofunctional mitochondrial response to methylglyoxal toxicity in Bufo bufo embryos

Methylglyoxal (2-oxopropanal) is a reactive alpha -oxoaldehyde that can be formed endogenously mainly as a by-product of glycolytic pathway. It is a c ytotoxic compound with significant antiproliferative properties as it can b ind, under physiological conditions, to nucleic acids and proteins, forming stable adducts. We have recently shown that exogenous methylglyoxal (150-6 00 muM) is highly toxic for amphibian embryos where it produces, when added to the culture water, inhibition of cell proliferation in the early develo pmental stages, followed by severe malformations and strongly reduced embry onic viability. In this work we investigate the morphofunctional effect of methylglyoxal on the common toad B. bufo embryo mitochondria in order to ve rify if its dysmorphogenetic action might be also ascribed to impairment of mitochondrial functions. The mitochondria were isolated from embryos at th e developmental Stages of morula, neural plate and operculum complete and d eveloping in the presence or 600 muM methylglyoxal. The results show that e xogenous methylglyoxal is highly toxic at mitochondrial level, where it pro duces proliferation, swelling and membrane derangement. As a consequence, m itochondria from treated embryos show decreased oxidative phosphorylation e fficiency, as indicated by the significant reduction both of the respirator y control index values and of the embryonic ATP content. On the basis of th ese data, it is possible that the methylglyoxal-induced embryonic malformat ions as well as the strongly reduced viability might be also ascribed to en ergy depletion. (C) 2001 Elsevier Science Ltd. All rights reserved.