Evaluation of toxicological effects induced by tributyltin in clam Ruditapes decussatus using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy: Study of metabolic responses in heart tissue and detection of a novel metabolite

Abstract

Tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Its toxicity in mollusks strongly affects their performance and survival. The main purpose of this study was to elucidate the mechanisms of TBT toxicity in clam Ruditapes decussatus by evaluating the metabolic responses of heart tissues, using high-resolution magic angle-spinning nuclear magnetic resonance (HRMAS NMR), after exposure to TBT (10−9, 10−6 and 10−4 M) during 24 h and 72 h. Results show that responses of clam heart tissue to TBT exposure are not dose dependent. Metabolic profile analyses indicated that TBT 10−6 M, contrary to the two other doses tested, led to a significant depletion of taurine and betaine. Glycine levels decreased in all clam groups treated with the organotin. It is suggested that TBT abolished the cytoprotective effect of taurine, betaine and glycine thereby inducing cardiomyopathie. Moreover, results also showed that TBT induced increase in the level of alanine and succinate suggesting the occurrence of anaerobiosis particularly in clam group exposed to the highest dose of TBT. Taken together, these results demonstrate that TBT is a potential toxin with a variety of deleterious effects on clam and this organotin may affect different pathways depending to the used dose.The main finding of this study was the appearance of an original metabolite after TBT treatment likely N-glycine-N′-alanine. It is the first time that this molecule has been identified as a natural compound. Its exact role is unknown and remains to be elucidated. We suppose that its formation could play an important role in clam defense response by attenuating Ca2+ dependent cell death induced by TBT. Therefore this compound could be a promising biomarker for TBT exposure.

Effects of hypoxia in the gills of the Manila clam Ruditapes philippinarum using NMR-based metabolomics

“…Consistent with previous studies (Hanana et al, 2014;Zhang et al, 2011), the NMR spectra of the gills from the clam R. philippinarum was dominated by organic osmolytes (Fig. 3).…”

Probing the interaction of a quercetin bioconjugate with Bcl‐2 in living human cancer cells with in‐cell NMR spectroscopy

“…The spectrum of intact cells demonstrated background signals of endogenous metabolites such as glucose in the region between 3–4 ppm and at 5.25 ppm attributed to the Ha proton, pyruvate at 2.2 and 2.4 ppm, alanine which is overlapping at 1.4 ppm etc. . Figure A represents the 1 H NMR spectrum of the quercetin‐alanine bioconjugate, which was a mixture of the main 3′ quercetin‐alanine analogue and the minor 4′ quercetin‐alanine product (Scheme S2A), annotated with purple and green colors, respectively.…”

Tributyltin and Zebrafish: Swimming in Dangerous Water

“…Also, a decrease in heart rate was reported, with the differential expression of important genes related to cardiac function and development, such as cav3 that encodes caveolin 3 protein and cmlc1 , which encodes cardiac myosin light chain-1 (essential for zebrafish cardiogenesis) ( 54 , 55 ). Other studies concerning cardiac function in TBT-treated animals were published revealing that this organotin induces cardiomyopathy in clam Ruditapes ( 56 ) and increased collagen deposition in heart interstice, impaired coronary vascular reactivity to estradiol, and enhanced the number of mast cells proximate to cardiac vessels in rats ( 57 ).…”