Neurotoxicity evaluation of meloxicam in the alternative in vivo model, Caenorhabditis elegans

Inflammatory processes cause changes in the permeability of the blood brain barrier. Non-steroidal anti-inflammatory drugs (NSAID) are most commonly used to treat these inflammatory processes, including meloxicam, and they can reach the central nervous system (CNS) and cause neurotoxicity. Since there are no studies evaluating the neurotoxicity of NSAID in alternative models of toxicity, the aim of this study was to evaluate the acute neurotoxicity (through nematodes changes in behavior) of meloxicam in an alternative in vivo model, Caenorhabditis elegans, as well as, to determine meloxicam toxicity through LD50 and development assessments. Meloxicam LD50 was high (50.03 mg/mL) and only the highest dose (100 mg/mL) caused a decrease in the nematode body size, indicating low toxicity in this alternative model. Besides, a neurological effect was observed only in the highest dose. Meloxicam showed neurotoxicity only at a very high dose, suggesting low potential to cause toxicity in the CNS. However, further studies are necessary to evaluate meloxicam neurotoxicity

Evaluation of the potential toxicity of haloperidol, clozapine and a new putative antipsychotic molecule, PT-31, in an alternative toxicity model, C. elegans

Schizophrenia is a disabling mental illness that affects approximately 1% of the world population. The treatment of this disorder is based on two generations of substances, typical antipsychotics, such as haloperidol, and atypical antipsychotics, such as clozapine, which can cause severe adverse effects. Therefore, the development of novel molecules that are safe and efficacious to treat the disease is crucial. PT-31 is a putative α2-adrenoceptor agonist effective against schizophrenia positive and cognitive symptoms in mice. C. elegans is an alternative model that has been successfully used to investigate the toxicity of a variety of substances. The present study aimed to evaluate the potential toxicity of the new molecule PT-31 and the antipsychotics haloperidol and clozapine in C. elegans. The evaluation was carried out based on toxicity endpoint tests, survival, developmental and behavioral assays. The antipsychotics haloperidol and clozapine decreased nematode survival by 30 and 40%, respectively, exposing the potential toxicity of these substances whereas PT-31 was safer based on this parameter. Similar results were obtained in the nematode developmental assay: haloperidol and clozapine significantly reduced nematode body length and area, whereas PT-31 preserved the normal development of the nematodes. The behavioral assessment was based on the frequency of body bends; none of the antipsychotics affected the locomotion rate of the nematodes, and PT-31 also did not compromise this parameter, demonstrating the safety of this new compound and reinforcing the recognized toxicity of antipsychotics

Water quality assessment in the region of Vale dos Sinos using the alternative model Caernorhabditis elegans

The determination of the condition of river water quality is critical to establishing sustainable water resource management policies. The use of bioindicators tests for the evaluation of water quality is a valuable tool, and the nematode C. elegans is described as a good organism to assess toxicological risks in aquatic and soil environments. The samples of water were collected in three stretches of the Paranhana and Ilha rivers (P1, P2 and P3) in November (spring) of 2018, January (summer) of 2019, April (autumn) of 2019, and August (winter) of 2019. The physic-chemical parameters were analyzed according to the standard methods (Standard Methods for the examination of Water and Wastewater 23rd edition). The nematode strains used are savage lineage N2 and were obtained through the Caenorhabidits Genetics Center (CGC) for the bioindicator test. The development evaluation was verified by the body surface area measurement of 20 nematodes which were quantified thru the ImageJ software. Most of the physic-chemical parameters were within the limits recommended by CONAMA, but aluminum, that presented values ten times higher than the recommended limit. Significant differences were observed in the nematodes development from all the samples when compared to the control group (p<0,001). The analysis of nematode development demonstrated that the bioindicator was sensitive to the research, showing that ecotoxicological assays are important for a more realistic scenario of threats to water quality, and C. elegans allows this assessment to be performed adequately.  The determination of the condition of river water quality is critical to establishing sustainable water resource management policies. In this scenario, the objective of this study is to verify the use the nematode Caenorhabidits elegans as a bioindicator test to evaluate water quality to assess toxicological risks in aquatic environment. The samples of water were collected in three stretches of the Paranhana and Ilha rivers (P1, P2, and P3) in November (spring) of 2018, January (summer) of 2019, April (autumn) of 2019, and August (winter) of 2019. The physicochemical parameters were analyzed according to the standard methods (Standard Methods for the examination of Water and Wastewater 23rd edition). The nematode strains used are savage lineage N2 and were obtained through the Caenorhabidits Genetics Center (CGC) for the bioindicator test. The development evaluation was verified by the body surface area measurement of 20 nematodes quantified through the ImageJ software. Most physicochemical parameters were within limits recommended by CONAMA, but aluminum presented values ten times higher than the recommended limit. Significant differences were observed in the nematode development from all the samples compared to the control group (p<0,001). The results obtained in this study, using C. elegans as a bioindicator, showed possible toxicological effects due to pollutants present in aquatic environment that can affect live organisms. The nematode C. elegans was sensitive, showing that ecotoxicological assays are important for a realistic scenario of threats to water quality