Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Abstract Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 µM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 µM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 µM) and CLO (0.01 and 1 µM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 µM. HAL and CLO present cytotoxicity at 0.1 µM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Permitted daily exposure from preclinical studies of Ginkgo biloba L. dry extract

Abstract Resolution 658/2022 of the Brazilian Regulatory Agency requires the determination of the permitted daily exposure (PDE) of pharmaceutical agents. Ginkgo biloba L. is used therapeutically to treat memory deficits and other brain diseases. However, published results indicate that more studies are needed to confirm the safety of Ginkgo biloba. This study aimed to evaluate the dry extract of Ginkgo biloba L. leaves PDE as an ingredient in an oral pharmaceutical product in preclinical studies using mice. Acute oral toxicity and repeated dose experiments were performed based on OECD guidelines, as well as genotoxicity tests. The results indicate that Ginkgo biloba L. has low acute toxicity, no liver toxicity, and does not alter blood glucose levels. No changes in weight gain were observed, but food intake decreased in males during the first week of treatment at the highest dose. Hematological parameters were not altered in males, whereas females presented lower leukocyte and lymphocyte counts and higher neutrophil counts at the highest dose. The lipid profile was not altered in males, whereas total cholesterol was increased in females. The estimated PDE was 0.1 mg/day and, when related to the maximum residual concentration, indicates that the cleaning process used is safe and does not require reassessment.

Impact of Anthropogenic Activities on Water Quality of The Paranhana River, Southern Brazil

Abstract: The Paranhana River, located in Southern Brazil, is one of the major tributaries of the Sinos River basin and receives mainly industrial and domestic effluents. In the present study, water physicochemical and microbiological analyses, condition factor, micronucleus test, gill histopathology and metal bioaccumulation in the muscle of the native fish Bryconamericus iheringii collected at two sites (S1 and S2) of the Paranhana River under different degrees of anthropogenic pressures were assessed in four sampling campaigns. Data from water quality parameters, condition factor, mucous cells proliferation in fish gills and bioaccumulation of chromium and manganese in muscle evidenced higher impacts at S2, whereas a higher genotoxic potential was observed at S1. Gill histopathological alterations were found in fish captured at both sampling sites. Temporal variations in all biomarkers analyzed and bioaccumulation of manganese and nickel were observed at S1, whereas only variations in condition factor, gill alterations and bioaccumulation of manganese and aluminum were found at S2. Our study evidences that S1 is under minor anthropogenic impacts and that the high urbanization at S2 reflects in a poor water quality. Nonetheless, the human consumption of fish from the Paranhana River should be avoided given the high concentrations of cadmium, chromium and lead.