Cytotoxicity of Nine Medicinal Plants from San Basilio de Palenque (Colombia) on HepG2 Cells.

The utilization of plants with medicinal properties is deeply rooted in the traditional knowledge of diverse human populations. This study aims to investigate the cytotoxicity of nine plants commonly used by communities in San Basilio de Palenque, Bolivar (Colombia), for managing inflammation-related illnesses. Hydroethanolic extracts from various plant parts such as roots, stems, barks, or leaves were prepared through a process involving drying, powdering, and maceration in an ethanol-water (7:3) solution. The extracts were subsequently freeze-dried and dissolved in DMSO for the bioassays. Cytotoxicity against the human hepatoma HepG2 cell line was assessed using the MTT assay, with extract concentrations ranging from 0 to 500 µg/mL and treatment durations of 24 and 48 h. The total phenolic content of the nine extracts varied from 96.7 to 167.6 mg GAE/g DT. Among them, eight hydroethanolic extracts from Jatropha gossypiifolia L., Piper peltatum L., Malachra alceifolia, Verbesina turbacensis, Ricinus communis, Desmodium incanum, and Dolichandra unguis-cati showed low toxicity (IC50 > 500 µg/mL, 24 h) against HepG2 cells. On the other hand, the extracts of Aristolochia odoratissima L. (IC50 = 95.7 µg/mL) and Picramnia latifolia (IC50 = 128.9 µg/mL) demonstrated the highest cytotoxicity against the HepG2 cell line, displaying a modest selectivity index when compared to the HEKn cell line after 48 h of treatment. These findings suggest that medicinal plants from San Basilio de Palenque, particularly Picramnia latifolia and Aristolochia odoratissima, have potential activity against cancer cells, highlighting their potential for further research and development.

Cytoprotective, Antiproliferative, and Anti-Oxidant Potential of the Hydroethanolic Extract of Fridericia chica Leaves on Human Cancer Cell Lines Exposed to α- and ß-Zearalenol.

Fridericia chica (Bignoniaceae) is a Colombian Caribbean plant with numerous health benefits, including properties such as wound healing, immune system stimulation, and antioxidant capacity, among others. Mycotoxins alpha-zearalenol (α-ZEL) and beta-zearalenol (ß-ZEL) are phase I metabolites of zearalenone, a natural product involved in endocrine disruption and cell proliferation processes. This study aimed to investigate the cytotoxic potential of the hydroethanolic extract of F. chica leaves (HEFc) and determine their protective effects against proliferation induced by α-ZEL and ß-ZEL on human hepatoma HepG2, lung cancer Calu-1, and primary normal human epidermal keratinocytes, neonatal (HEKn). The cytotoxicity of HEFc was measured in a range from 4 to 1000 µg/mL and from 0.4 to 100 µM for both α-ZEL and ß-ZEL. Cell production of intracellular ROS was monitored using the H2-DCFDA probe. The cells exposed to HEFc presented IC50 of 128, 249, and 602 µg/mL for the HepG2, Calu-1, and HEKn cells, respectively. A greater selectivity was seen in HepG2 cells [selectivity index (SI) = 3.5] than in Calu-1 cells (SI = 2.4). Cells treated with mycotoxins remained viable during the first day, and cell proliferation increased at low tested concentrations (0.4-6.3 µM) in all three cell lines. However, after 48 h treatment, cells exposed to 50 and 100 µM of α-ZEL and ß-ZEL displayed decreased viability. HEFc at 16 µg/mL was able to give some protection against cytotoxicity induced by high concentrations of ß-ZEL in HepG2, reducing also cell proliferation elicited at low levels of α-ZEL and ß-ZEL. ROS production was not observed in cells treated with this HEFc concentration; however, it prevented ROS formation induced by treatment with 50 µM α-ZEL or ß-ZEL. In summary, HEFc isolated from plants grown in northern Colombia displayed promising results against cell proliferation and oxidative stress caused by mycotoxins.

Hydroalcoholic extract of Haematoxylum brasiletto protects Caenorhabditis elegans from cadmium-induced toxicity.

BACKGROUND: H. brasiletto is used in popular culture due to its therapeutic properties, including antioxidant, anti-inflammatory and antiproliferative properties, although little is known about its role as a protector against metal toxicity. This study aimed to investigate the chemical composition and efficacy of the hydroalcoholic extract from H. brasiletto (HAE-Hbrasiletto) collected in northern Colombia to defend against cadmium (Cd)-induced toxicity. METHODS: Phytochemical characterization was performed using HPLC-ESI-QTOF. Caenorhabditis elegans was employed to assess the shielding effect of HAE-Hbrasiletto against Cd toxicity in vivo, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was utilized to measure radical scavenging activity. RESULTS: The main secondary metabolites identified by HPLC-ESI-QTOF in the extracts were hematoxylins (brazilein and hematein) and protosappanins (protosappanin A, B and C, 10-O-methylprotosappanin B, and protosappanin A dimethyl acetal). The HAE-Hbrasiletto elicited low lethality in N2 worms and significantly reduced the Cd-induced death of the nematodes. It also improved Cd-induced motility inhibition, as well as body length and reproduction reduction provoked by the heavy metal. The extract displayed a good capacity to halt Cd-induced DAF-16 translocation. As this last process was associated with lethality (r = 0.962, p < 0.01), the antioxidant properties of the extract may contribute to ameliorating tissue damage induced by oxidative stress from Cd exposure. CONCLUSION: HAE-Hbrasiletto has remarkable properties to protect against Cd-induced toxicity.

Biomonitoring of Lead Exposure in Children from Two Fishing Communities at Northern Colombia.

Lead (Pb) exposure is a growing concern in developing countries, especially in vulnerable children. The objective of this study was to evaluate blood lead levels (BLL) in children from two fishing populations at Northern Colombia, Loma de Arena and Tierrabomba, as well as their association with morphometric parameters, markers of hematological status, liver function, and mRNA expression of genes related to Pb toxicity. A total of 198 blood samples were collected from participants aged 5-16 years old. The mean (± standard error) BLL for the studied sample was 3.6 ± 0.3 µg/dL, and the 97.5th percentile was 21.0 µg/dL. The participants of Loma de Arena and Tierrabomba presented BLL of 3.9 ± 0.5 and 2.9 ± 0.3 µg/dL, respectively. Children born preterm had greater BLL than those born at full term. Boys had greater BLL than girls, which also occurred for participants between 12 and 16 years old, compared with those aged 5-11 years old. The BLL were negatively correlated with body mass index in children from Loma de Arena, but an opposite behavior was observed for Tierrabomba. In Loma de Arena, the mRNA expression of interferon gamma, a pro-inflammatory cytokine, increased with the BLL, but that of δ-aminolevulinic acid dehydrogenase, a sensor for Pb poisoning, decreased. In Tierrabomba, gene expression did not change with BLL. These results show that in fishing communities, lead exposure promotes different health impacts depending on age, sex, and other site-specific factors. In any case, appropriate educational and intervention programs should be carried out to minimize Pb exposure in children.

Protective Effects of the Hydroethanolic Extract of Fridericia chica on Undifferentiated Human Neuroblastoma Cells Exposed to α-Zearalenol (α-ZEL) and ß-Zearalenol (ß-ZEL).

Fridericia chica (Bignoniaceae) is a traditional medicinal plant. The aim of this research was to determine the protective effects of the hydroethanolic extract from the F. chica leaves (HEFc) against the cytotoxicity of zearalenone (α-ZEL) and ß-ZEL on SH-SY5Y cells. Free radical scavenging activity of HEFc was evaluated using the DPPH method. The cytotoxicity of both zearalenone metabolites and HEFc was examined using MTT test, as was the cytoprotective effects of the HEFc on cells treated with these mycotoxins. The chemical composition of HEFc was determined using UPLC-QTOF-MS/MS. HEFc elicited good DPPH radical scavenging activity following a concentration-dependent relationship. Cells exposed to α-ZEL exhibited a viability ˂50% after 48 h of treatment (25 and 50 µM), while those exposed to ß-ZEL showed viability ˂50% (100 µM) and ˂25% (25-100 µM) after 24 and 48 h of exposure, respectively. HEFc showed a significant increase in cell viability after exposure to α-ZEL (25 and 50 µM) and ß-ZEL (6-100 µM) (p < 0.05). UPLC-QTOF-MS/MS analyses allowed the identification of 10 phytochemical components in the HEFc. In short, the hydroethanolic extract of F. chica grown in Colombian Caribbean can protect against the effects of mycotoxins and it is a valuable source of compounds with antioxidant properties.

Oxidative stress, glutathione, and gene expression as key indicators in SH-SY5Y cells exposed to zearalenone metabolites and beauvericin.

The co-presence of mycotoxins from fungi of the genus Fusarium is a common fact in raw food and food products, as trace levels of them or their metabolites can be detected, unless safety practices during manufacturing are carried out. Zearalenone (ZEA), its metabolites α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL) and, beauvericin (BEA) are co/present in cereals, fruits or their products which is a mixture that consumer are exposed and never evaluated in neuronal cells. In this study the role of oxidative stress and intracellular defense systems was assessed by evaluating reactive oxygen species (ROS) generation and glutathione (GSH) ratio activity in a human neuroblastoma cell line, SH-SY5Y cells, treated individually and combined with α-ZEL, ß-ZEL and BEA. It was further examined the expression of genes involved in cell apoptosis (CASP3, BAX, BCL2) and receptors of (endogenous or exogenous) estrogens (ERß and GPER1), by RT-PCR in those same conditions. These results demonstrated elevated ROS levels in combinations where α-ZEL was involved (2.8- to 8-fold compared to control); however, no significant difference in ROS levels were detected when single mycotoxin was tested. Also, the results revealed a significant increase in GSH/GSSG ratio at all concentrations after 24 h. Expression levels of CASP3 and BAX were up regulated by α-ZEL while CASP3 and BCL2 were down regulated by ß-ZEL, revealing how ZEA´s metabolites can induce the expression of cell apoptosis genes. However, BEA down-regulated the expression of BCL2. Moreover, ß-ZEL + BEA was the only combination treatment which was able to down regulate the levels of cell apoptosis gene expression. Relying to our findings, α-ZEL, ß-ZEL and BEA, induce injury in SH-SY5Y cells elevating oxidative stress levels, disturbing the antioxidant activity role of glutathione system and finally, causing disorder in the expressions and activities of the related apoptotic cell death genes.

Toxicological effects in children exposed to lead: A cross-sectional study at the Colombian Caribbean coast.

Lead (Pb) is an environmental pollutant with a toxicity that is a serious public health problem. The aim of this research was to evaluate the associations between Pb exposure and morphometric, hematological and biochemical parameters, mRNA expression of the P53, SOD1, ALAD, TNF and INF-γ genes, ALAD polymorphisms (db SNP ID: rs1800435) and Intelligence Quotient (IQ) in children from the Colombian Caribbean. Blood lead levels (BLL) were determined in 554 participants between the ages of 5-16 years old, from different places of the Colombian Caribbean. A health survey was given to assess risk factors. Whole blood was used for hematology and plasma employed to analyze markers of hepatic toxicity. Gene expression was quantified from blood mRNA by RT-PCR. The ALAD polymorphism was characterized by PCR-RFLP, and the Kaufman's brief intelligence test was employed to estimate the IQ. The mean BLL was 3.5 ±â€¯0.2 µg/dL. The site of greatest exposure to Pb was Tasajera, a poor fishing community, with an average of 8.9 ±â€¯0.8 µg/dL. Breastfeeding was associated with high BLL. Morphometric characteristics and IQ were negatively correlated with BLL. The blood platelet count and the mean corpuscular hemoglobin concentration showed positive and negative correlations with BLL, respectively. Negative relationships with BLL were observed with the ratios Neutrophils/Eosinophils and Neutrophils/Basophils, whereas for BLL and Neutrophils/Monocytes the association was positive. The associations between morphometric and some hematological parameters with BLL were age- and gender-related. The expression of ALAD, SOD1, INF-γ and P53 mRNA was down-regulated according to the BLL, whereas TNF showed an opposite trend. In short, fishing communities are at a high risk of Pb exposure. This xenobiotic can affect physical development and IQ, as well as hematological parameters, even at low concentrations. In addition, it can regulate the transcription of genes associated with inflammation, apoptosis, cell cycle, heme synthesis, and oxidative stress.

Low blood lead levels impair intellectual and hematological function in children from Cartagena, Caribbean coast of Colombia.

Lead produces numerous biochemical and physiological changes in humans, including hematological disorders, toxic effects on the central nervous system and in the function of several organs. The aim of this study was to determine blood lead levels (BLL) in children from Cartagena, Colombia, associating those with hematological and liver damage markers, the intelligence quotient (IQ), as well as with gene expression of the aminolevulinate dehydratase (ALAD), superoxide dismutase 1 (SOD1), gamma interferon (INF-γ), tumor necrosis factor (TNF) and tumor protein (p53). To achieve this purpose, 118 blood samples were collected from children 5-16 years old, with their respective informed consent from their parents. BLL was measured by atomic absorption; hematological parameters were obtained with automated systems; plasma was utilized to analyze hepatic toxicity markers, alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP); the Kaufman Brief Intelligence Test (K-BIT) was administered to measure the IQ; and gene expression was quantified from blood RNA. The mean BLL was 1.7±0.3µg/dL. A low proportion of the children (3.4%) had BLL above the CDC recommended limit (5µg/dL). BLL were correlated weakly, but negatively with child age, weight, height, body mass index, platelets wide distribution, mean platelet volume, γ-GT and IQ. There were not significant changes in the expression of evaluated genes. These results support the hypothesis that BLL below 5µg/dL may still be a detrimental factor on children's cognitive abilities, development and hematology, in line with recent concerns that there is no safe level of pediatric lead exposure.

Eriptosis: mecanismos moleculares y su implicación en la enfermedad aterotrombótica / Eryptosis: molecular mechanisms and their implications in atherothrombotic disease

Introducción: La eriptosis se ha descrito como el proceso de muerte celular programada en el eritrocito antes de la senectud. Puede desencadenarse en situaciones como: el estrés osmótico, el estrés oxidativo, la exposición a metales pesados, entre otros factores. Diversos estudios sugieren que los eritrocitos pueden desempeñar un papel activo en la hemostasia normal o anormal en ciertas condiciones en las que se produce perturbación de la membrana de estas células. Objetivo: Describir los mecanismos involucrados en la eriptosis y su estrecha relación con los procesos de adhesión a la pared vascular que conllevan a la enfermedad trombótica. Método: Se hizo una revisión narrativa a partir de la literatura encontrada en las bases de datos PubMed y Science Direct utilizando las palabras claves. Se seleccionaron 51 artículos originales, 20 revisiones de la literatura y un estudio de casos, que se ajustaban a las exigencias del objetivo. Se revisaron los resúmenes de forma separada e independiente. Seguidamente se buscaron las publicaciones en el texto completo para la revisión. Conclusiones: La eriptosis se caracteriza por la disminución del volumen celular, la vesiculación y la translocación del fosfatidil serina hacia la superficie externa de la membrana plasmática. Las alteraciones en la distribución de los fosfolípidos favorecen los procesos de adhesión celular a la pared vascular, conllevando al deterioro de la microcirculación, lo cual puede ocasionar importantes trastornos a nivel cardiovascular. La comprensión y el esclarecimiento de la eriptosis pueden ser esenciales para la búsqueda de nuevas dianas terapéuticas, encaminadas a ofrecer otras alternativas farmacológicas en el tratamiento de la enfermedad cardiovascular.

Introduction: Eryptosis has been described as programmed process of cellular death in erythrocytes before old age. It can be triggered, among other factors, by situations such as osmotic stress, oxidative stress or exposure to heavy metals. Several studies suggest that erythrocytes can play an active role in normal or abnormal haemostasis in certain conditions where the membrane of these cells is perturbed. Objetive: To describe the mechanisms involved in eryptosis and their close relationship with the processes of adhesion to the vascular wall that entail the thrombotic disease. Methods: A narrative review was carried out from the literature found in data base PubMed and Science Direct by using the key words. 51 original articles, 20 literature reviews and one case study complying with the requirements were selected. Abstracts were reviewed separately and independently. Complete publications were then located for review. Conclusions: Eryptosis is characterised by the decrease in cell volume, the vesiculation and the translocation of phosphatidylserine towards the outer surface of the plasma membrane. Disorders in the distribution of the phospholipids favour processes of cell adhesion to the vascular wall, causing impairment of microcirculation, which can result in important cardiovascular diseases. Understanding and clarifying eryptosis could be essential for finding new therapeutic targets, aimed at offering other pharmacological alternatives for the treatment of cardiovascular diseases.