Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats.

BACKGROUND: Ischemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats. METHODS: Twenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1ß, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization. RESULTS: The administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1ß and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.

Virus del papiloma humano en carcinoma colorrectal / Human papilloma virus in colorectal carcinoma

Resumen Introducción: Previos trabajos han reportado una asociación entre la infección del virus del papiloma humano (VPH) y el desarrollo de cáncer colorrectal, aunque existe controversia al respecto. Materiales y Método: Estudio observacional, transversal, descriptivo, retrospectivo, no ciego. Se utilizaron 50 muestras de patología con diagnóstico de adenocarcinoma colorrectal, incluidas en parafina, para aislar ADN de las muestras. Se realizó la extracción de ADN mediante protocolos establecidos para extracción, lisis y rehidratación de muestra. Se identificó y genotipicó el ADN del virus para amplificar y detectar subtipos oncogénicos de entre 35 subtipos diferentes incluidos en la prueba, secuenciando las muestras positivas, utilizando protocolos ya establecidos de purificación y análisis de muestra, mediante microarreglos. Resultados: Se identificaron 14 muestras de 50 (28%) estudiadas positivas para el virus de papiloma humano de las cuales 11 (22%) incluyen uno o más subtipos de alto riesgo para neoplasia. No se identificaron diferencias estadísticamente significativas entre grupos en cuanto a edad, sexo, localización del tumor, grado de diferenciación, infiltración, ganglios afectados, metástasis o número de paquetes/año. Conclusión: La detección de los subtipos de VPH de alto riesgo en un alto porcentaje de las muestras positivas, sugiere una asociación entre la infección con el desarrollo de cáncer colorrectal.

Introduction: Previous works have reported an association between human papilloma virus (HPV) infection and the development of colorectal cancer, and although controversy regarding this association exists. Materials and Method: This was an observational, cross-sectional, descriptive, retrospective unblinded study. Fifty pathology samples embedded in paraffin with a diagnosis of colorectal adenocarcinoma were used to isolate DNA from the tissue. DNA was extracted according to established protocols for extraction, lysis and sample rehydration. Viral DNA was identified and genotypified to amplify and detect oncogenic subtypes among 35 different subtypes included in the study, sequencing positive samples with established protocols of purification and sample analysis using microarrays. Results: Fourteen of 50 (28%) samples were identified as positive for human papilloma virus; of these 11 (22%) included one or more high-risk subtypes for neoplasia. Statistically significant differences were not found between the groups regarding age, sex, tumor location, degree of differentiation, infiltration, affected lymph nodes, metastasis and number of pack years. Conclusion: The detection of high-risk VPH subtypes in a high percentage of positive samples, suggests an association between infection and the development of colorectal cancer.