Unraveling the metabolomic profile and acute toxicity of ethanolic extract from Mimosa tenuiflora (Willd.) Poir. root bark.

Mimosa tenuiflora (Fabaceae) is popularly known in Brazil as "Jurema preta". From the bark of its root, "jurema wine" is obtained, a psychedelic drink used in Indigenous religious rituals in Northeastern Brazil. This work aimed to investigate the chemical composition and acute oral toxicity of the ethanolic extract of the root bark from M. tenuiflora (EEMt). EEMt was analyzed by UPLC-QToF-MS/MS and DI-ESI-IT-MSn. Oral administration of EEMt was performed once at doses of 300 and 2000 mg/kg in female Swiss mice. Signs and symptoms of intoxication, as well as mortality were monitored for 14 days. Thirteen compounds were annotated in EEMt: eight type B proanthocyanidins, three alkaloids, a glycosylated flavonol, and a dihydrochalcone derivative. The acute administration of 300 and 2000 mg/kg of EEMt did not show mortality. It also did not change the food intake or body weight of the animals. However, the relative weights of the kidneys were significantly changed for both doses. Changes in hematological and biochemical parameters were found. In addition, histopathological changes were also observed in the heart, liver, and kidneys. Thus, based on our findings, EEMt presented an LD50 greater than 2000 mg/kg and was therefore classified in category 5 of the Globally Harmonized Classification System (GHS). EEMt showed acute oral toxicity by altering hematological, biochemical and histological parameters.

Acute Oral Toxicity Evaluation of Almond Hull Powders in BALB/c Mice.

Almond hull, a substantial byproduct constituting more than half of almond fresh weight, has garnered recent attention due to its abundance in fiber and bioactive content. Despite this huge interest, data on its toxicity remain scarce. In line with the Organization for Economic Cooperation and Development (OECD) 423 guidelines, this study conducted an acute oral toxicity test using almond hull powders processed from three major almond varieties of Butte, Monterey, and Nonpareil on BALB/c female mice, administering dosages of 300 mg/kg body weight (bw), 2000 mg/kg bw, and 5000 mg/kg bw, with observations over a 14-day period. The results indicated that almond hull powders were non-toxic, aligning with the Globally Harmonized System's classification. Administering up to 5000 mg/kg bw of all three varieties of almond hull powders (female BALB/c mice) and 10,000 mg/kg bw of Monterey almond hull powders (both female and male mice) induced no adverse effects in terms of mortality, body weight changes, food intake, organ to weight ratio, and clinical biochemistry. Additionally, histopathological examination revealed no organ abnormalities. This study demonstrates the non-toxic nature of almond hull as an edible food ingredient under experimental conditions, encouraging the further exploration of its potential for safe consumption and its health benefits.

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds.

Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1, BCL2, and FLT3. The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

Investigations on acute oral toxicity studies of purpurin by application of OECD guideline 423 in rodents.

The anticancer, anti-inflammatory and antioxidant properties of Purpurin were generated from in vitro studies, and no scientific reports were found on its safety and efficacy, related to their in vivo studies; thus, the present study was focused on acute oral toxicity of purpurin in female Wistar rats as per the OECD 423 guidelines. In this study, purpurin was administered at starting dosage of 300 mg/kg followed by 2000 mg/kg, p.o, and animals were observed for toxic signs at 24 h and for the next 14 days to different animal groups. Animals were observed for mortality, behavioral changes, biochemistry, hematological parameters, and histopathological examination after a follow up on the 14th day. The oral lethal dose for mice was greater than 2000 mg/kg, b.wt. in female rats and classified under category 5 as per the acute oral toxicity study. It was found that there were no significant differences in body weight changes, food/water intake, hematology, and clinical biochemistry. The histopathological study directly depicted that there were no pathological changes observed in the vital organs of rats treated with the different dose of Purpurin. The present work advocates that an acute oral administration of Purpurin was found to be a non-toxic and safe drug in the tested experimental conditions.

Preclinical toxicity of innovative molecules: In vitro, in vivo and metabolism prediction.

The lack of predictivity of animal's models has increased the failure rate of drug candidates. Thus, the reversion of this scenario using preliminary in vitro assays and metabolism prediction can reduce the unnecessary use of animals, as well as predict toxic effects at preclinical and clinical stages. The present study aimed to evaluate safety of four biologically active molecules (RN104, RI78, ICH, PCH) with potential therapeutic applications synthesized in our laboratory. Initially, we used MTT cytotoxicity against A549, H9C2, HepG2, LLC-PK1 and NEURO-2 cell lines. RN104 showed the lowest cytotoxicity and further studies were conducted with it. The neutral red (NR) test was performed according to OECD-129 and then acute toxicity test (OECD-423). According to NR results we administered at 300 mg/kg on animals; however, no toxic effect was observed, while 2,000 mg/kg resulted in the death of one animal per group. After, metabolism prediction studies, performed using both ligand-based and structure-based, suggests three potential metabolites. In silico results suggested that potential metabolites could be fast eliminated and, then, this could be an explanation for lower observed toxicity in in vivo experiments. The results showed limitations of the NR as a predictor of the initial dose for the acute toxicity study, which may be related to metabolism. Therefore, the combination of theoretical and experimental studies is relevant to a general understanding of new molecule's toxicity.

Luminescent Marker for GSR: Evaluation of the Acute Oral and Inhalation Toxicity of the MOF [Eu(DPA)(HDPA)].

The metal-organic framework (MOF) [Eu(DPA)(HDPA)] (where DPA is dipicolinic acid) has been previously reported as an efficient marker for gunshot residues (GSRs). Since this marker will be in contact with various shooters, industrial workers, and the environment, however, it is important to identify its toxicity. In this work, the oral and the inhalation acute toxicities of the MOF [Eu(DPA)(HDPA)] (also called R-Marker) were evaluated in young Wistar rats using Guidelines 423 (oral) and 436 (inhalation) from the Organisation for Economic Co-operation and Development (OECD). Animal behavior; body weight, water, and food intake; and organ weight, as well as biochemical parameters were evaluated in both evaluations. For the inhalation test, a concentration of 1 mg·Lair-1·(4 h-1) was reached in a whole-body inhalation chamber. When the respiratory tract was analyzed, it was observed that part of the marker had been swallowed instead of inhaled by the animal. For the oral test, the highest administrated dose was 2000 mg/kg with no sign of toxicity. This marker has been classified in the least toxic category of the Globally Harmonized System (GHS; category 5), with an oral median lethal dose (LD50) of 5000 mg/kg. After the oral administration, the feces of the animals were collected using a metabolic cage. Luminescent feces were present up to 24 h after administration, indicating that the marker had been excreted by the organism without causing intoxication. This study has opened perspectives for drug delivery and toxicity studies, since it enables visual detection of the marker.

Application of the Metal-Organic Framework [Eu(BTC)] as a Luminescent Marker for Gunshot Residues: A Synthesis, Characterization, and Toxicity Study.

The 3D metal-organic framework (MOF) [Eu(BTC)] (where BTC = trimesic acid) was synthesized in 20 min by a microwave-assisted hydrothermal method with a yield of 89%. A structural and spectroscopic study, performed by X-ray diffraction, thermogravimetry, and photoluminescence spectroscopy, showed that this framework has high crystallinity, thermal stability, and luminescence. This MOF had a red-orange luminescence when excited with ultraviolet (UV) radiation (λ = 254 nm) and a high potential for use as a luminescent marker for gunshot residues (GSR). When added to 9 mm nontoxic ammunition, it greatly improved quality of the crime scene investigation, allowing for direct visualization of the luminescent GSR on the shooter's hand and firearm and at the firing range using only a portable UV lamp. The marked luminescent GSR was easily collected and characterized by nondestructive techniques, including with a Video Spectral Comparator and scanning electron microscopy/energy-dispersive spectroscopy, wherein the presence of Eu3+ ions was confirmed. Furthermore, the oral acute toxicity of this MOF was assessed in adult female Wistar rats using the Organisation for Economic Cooperation and Development 423 guidelines. This study classified the MOF [Eu(BTC)] in a less toxic Globally Harmonized System category (category 5), with a LD50 (lethal dose) of 5000 mg/kg, ensuring a wide security range for its application.