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 cytotoxic compound with significant antiproliferative properties as it can bind, under physiological conditions, to nucleic acids and proteins, forming stable adducts. We have recently shown that exogenous methylglyoxal (150-600 microM) is highly toxic for amphibian embryos where it produces, when added to the culture water, inhibition of cell proliferation in the early developmental stages, followed by severe malformations and strongly reduced embryonic viability. In this work we investigate the morphofunctional effect of methylglyoxal on the common toad B. bufo embryo mitochondria in order to verify if its dysmorphogenetic action might be also ascribed to impairment of mitochondrial functions. The mitochondria were isolated from embryos at the developmental stages of morula, neural plate and operculum complete and developing in the presence of 600 microM methylglyoxal. The results show that exogenous methylglyoxal is highly toxic at mitochondrial level, where it produces proliferation, swelling and membrane derangement. As a consequence, mitochondria from treated embryos show decreased oxidative phosphorylation efficiency, as indicated by the significant reduction both of the respiratory control index values and of the embryonic ATP content. On the basis of these data, it is possible that the methylglyoxal-induced embryonic malformations as well as the strongly reduced viability might be also ascribed to energy depletion.
Amicarelli
F
F
Dipartimento di Biologia di Base ed Applicata, Facoltà di Scienze, Università degli Studi di L'Aquila, Coppito 67100, L'Aquila, Italy. vito@ing.univaq.it
Colafarina
S
S
Cesare
P
P
Aimola
P
P
Di Ilio
C
C
Miranda
M
M
Ragnelli
A M
AM
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002023:Bufo bufo / Q000196:embryology / Q000378:metabolism*; D019069:Cell Respiration / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D011765:Pyruvaldehyde / Q000633:toxicity*; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000244:Adenosine Diphosphate; D011765:Pyruvaldehyde; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase