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.

Trypanosoma cruzi Letm1 is involved in mitochondrial Ca2+ transport, and is essential for replication, differentiation, and host cell invasion.

Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca2+ and K+ homeostasis in mammalian cells. Here, we demonstrate that the Letm1 orthologue of Trypanosoma cruzi, the etiologic agent of Chagas disease, is important for mitochondrial Ca2+ uptake and release. The results show that both mitochondrial Ca2+ influx and efflux are reduced in TcLetm1 knockdown (TcLetm1-KD) cells and increased in TcLetm1 overexpressing cells, without alterations in the mitochondrial membrane potential. Remarkably, TcLetm1 knockdown or overexpression increases or does not affect mitochondrial Ca2+ levels in epimastigotes, respectively. TcLetm1-KD epimastigotes have reduced growth, and both overexpression and knockdown of TcLetm1 cause a defect in metacyclogenesis. TcLetm1-KD also affected mitochondrial bioenergetics. Invasion of host cells by TcLetm1-KD trypomastigotes and their intracellular replication is greatly impaired. Taken together, our findings indicate that TcLetm1 is important for Ca2+ homeostasis and cell viability in T cruzi.

Impact of early malnourishment on the chronic inflammatory response and its implications for the effect of indomethacin on Wistar rats.

The objective of the present study was to investigate whether early undernutrition changes the chronic inflammatory response, so as to study its influence on pharmacological response to indomethacin. Rat offspring of dams fed from the first day of gestation to term or throughout the lactation period received a balanced diet (NN) or a basic regional diet (BRD) from northeast Brazil. According to their dams, the offspring were divided into three groups: NN; basic regional diet during gestation (BRD-g, undernourished during gestation); basic regional diet during gestation and lactation (BRD-gl, undernourished during gestation and lactation). At 2 months of age, Freund's adjuvant (0·2 ml) was inoculated into the plantar surface of the hind paw (day 0) of animals. All animals orally received saline (0·9 %) for 28 d. Another group of adult offspring was subjected to the same procedure as described above, but orally received indomethacin (2 mg/kg) instead of saline, and divided into three subgroups: NN treated with indomethacin (NNI); BRD-g treated with indomethacin (BRDI-g); BRD-gl treated with indomethacin (BRDI-gl). The hind paw volume was calculated on days 0 (initial paw volume), 7, 14 and 28. Hind paw swelling, blood albumin and C-reactive protein (CRP) levels and leucocyte counts were evaluated as markers of inflammation. Reduced hind paw swelling and the blood levels of serum albumin and CRP were found in the BRD-g and BRD-gl offspring. However, no difference was found in the leucocyte count. Compared with their respective saline-treated groups (NN, BRD-g and BRD-gl), the anti-inflammatory effect of indomethacin was lower in the BRDI-g and BRDI-gl groups than in the NNI group. We conclude that early undernutrition attenuated the chronic inflammatory response and the anti-inflammatory effect of indomethacin.