NMR-based metabolomics analysis reveals the effect of environmental contamination exposure on fishermen living around the Mundaú Lagoon in Maceió (Alagoas, Brazil).

The Mundaú lagoon in Maceió (Alagoas, Brazil) is a crucial resource for the local population, particularly fishing communities. Recent studies have revealed potential toxic metal contamination in the lagoon, particularly with mercury (Hg) levels exceeding the maximum regulated values. This inorganic contaminant may be impacting the health of fishermen and the local population. In this context, metabolomics, a study of small-molecule metabolites, can offer insights into the physiological impact of environmental contamination on humans. Thus, volunteers from the control and exposed groups were selected, considering the main exposure criteria primarily defined by their proximity and interaction with the lagoon. Blood and urine samples were collected from the volunteers and subjected to analysis using NMR spectroscopy. The data underwent Principal Component Analysis (PCA) and Orthogonal Partial Least-Squares Discriminant Analysis (OPLS-DA) based on metabolic patterns to establish group discrimination or identification. Metabolic pathways were assessed through enrichment analysis. The study revealed several metabolic disturbances in the exposed group's urine and plasma samples compared to control group. Noteworthy findings included arginine and proline metabolism disruptions, indicative of ammonia recycling and urea cycle impairment. These changes suggest compromised ammonia detoxification in the exposed group. Disturbances in the tricarboxylic acid (TCA) cycle and the transfer of acetyl groups into mitochondria suggested systemic metabolic stress in energy metabolism. Furthermore, elevated carnitine and ketone levels may indicate compensatory responses to low TCA cycle activity. Alterations in glutamate and glutathione metabolism and imbalances in glutathione levels indicate oxidative stress and impaired detoxification. This study highlights significant metabolic changes in fishermen exposed to contaminated environments, which can affect various metabolic pathways, including energy metabolism and antioxidant processes, potentially making individuals more vulnerable to the adverse effects of environmental contaminants. Finally, this work highlights insights into the relationship between environmental contamination and metabolic pathways, particularly in regions with limited studies.

Synthesis and anti-ureolitic activity of Biginelli adducts derived from formylphenyl boronic acids.

Urease is a metalloenzyme that contains two Ni(II) ions in its active site and catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The development of effective urease inhibitors is crucial not only for mitigating nitrogen losses in agriculture but also for offering an alternative treatment against infections caused by resistant pathogens that utilize urease as a virulence factor. This study focuses on synthesizing and investigating the urease inhibition potential of Biginelli Adducts bearing a boric acid group. An unsubstituted or hydroxy-substituted boronic group in the Biginelli adducts structure enhances the urease inhibitory activity. Biophysical and kinetics studies revealed that the best Biginelli adduct (4e; IC50 = 132 ± 12 µmol/L) is a mixed inhibitor with higher affinity to the urease active site over an allosteric one. Docking studies confirm the interactions of 4e with residues essential for urease activity and demonstrate its potential to coordinate with the nickel atoms through the oxygen atoms of carbonyl or boronic acid groups. Overall, the Biginelli adduct 4e shows great potential as an additive for developing enhanced efficiency fertilizers and/or for medical applications.