Paracetamol poisoning induces acute liver injury in rats: inhibition of miR-155/cd45 axis-mediated antioxidant depletion and hepatotoxicity using quercetin and resveratrol / La intoxicación por paracetamol induce daño hepático agudo en ratas: inhibición de la depleción de antioxidantes mediado por el eje miR-155/cd45 y hepatotoxicidad usando quercetina y resveratrol

SUMMARY: Ingestion of an overdose of paracetamol (also called acetaminophen, or APAP) induces hepatotoxicity that can lead to liver failure. The link between the pro-inflammatory microRNA-155 (miR-155) and leukocyte infiltration (CD45) in APAP- antioxidant depletion and liver toxicity with and without the natural polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) has not been previously studied. Therefore, acute hepatic injury was induced in rats by 2 g/kg APAP (single dose, orally) and another group started QUR (50 mg/kg) plus RES (30 mg/kg) treatment one week prior to APAP ingestion. Animals were culled 24 hours post the paracetamol treatment. APAP overdose induced hepatic and blood levels of miR-155 expression, CD45 (leukocyte common antigen) immunostaining, degenerated hepatocytes, and hepatic injury enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which were markedly decreased by QUR+RES. Whereas, APAP intoxication ameliorated liver tissue levels of the antioxidants, glutathione peroxidase and superoxide dismutase that were augmented by QUR+RES. Moreover, a significant (p<0.05) correlation between miR-155/CD45 axis and liver tissue injury was observed. These findings show that paracetamol intoxication augments miR- 155/CD45 axis-mediated modulation of antioxidants and liver injury in rats, and is protected by QUR+RES.

RESUMEN: La ingestión de una sobredosis de paracetamol (también llamado acetaminofeno o APAP) induce hepatotoxicidad que puede provocar insuficiencia hepática. El vínculo entre el microARN-155 proinflamatorio (miR-155) y la infiltración de leucocitos (CD45) en el agotamiento de APAP- antioxidante y la toxicidad hepática con y sin los compuestos polifenólicos naturales, quercetina (QUR) más resveratrol (RES) no ha sido previamente investigado. En este estudio, se indujo daño hepático agudo en ratas con 2 g/kg de APAP (dosis única, por vía oral) y otro grupo comenzó el tratamiento con QUR (50 mg/ kg) más RES (30 mg/kg) una semana antes de la ingestión de APAP. Los animales se sacrificaron 24 horas después del tratamiento con paracetamol. La sobredosis de APAP indujo niveles hepáticos y sanguíneos de expresión de miR-155, inmunotinción de CD45 (antígeno leucocitario común), degeneración de los hepatocitos y daño hepático enzimático; alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST), disminuyeron notablemente con QUR+RES. Mientras que la intoxicación con APAP mejoró los niveles de antioxidantes, glutatión peroxidasa y superóxido dismutasa en el tejido hepático los que aumentaron con QUR+RES. Además, se observó una correlación significativa (p<0,05) entre el eje miR-155/CD45 y la lesión del tejido hepático. Estos hallazgos muestran que la intoxicación por paracetamol aumenta la modulación mediada por el eje miR-155/CD45 de los antioxidantes y la lesión hepática en ratas, y está protegida por QUR+RES.

Thyroid disorders, epidemiology and outcome among patients in South Western region: Southern Saudi Arabia

Background: Thyroid gland may have a group of a medical condition that affects its main function. The thyroid gland is located at the front of the neck and produces thyroid hormones. The released hormones go through the blood to many body organs for regulating their function, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development. The study aimed to assess the epidemiology of thyroid disorders among cases in the south-western region, Saudi Arabia, and to assess the reporting quality for these cases data.Methods: A retrospective record based descriptive approach was used through reviewing medical records of all cases that were admitted and diagnosed as thyroid related disorders for different indications in the main hospital (king Khalid Hospital) during the period from January 2018 to January 2020. Data extracted throng pre-structured questionnaire including patient's bio-clinical data, preoperative radiological and laboratory investigations. Also, laryngoscope pre and post operatively was reviewed to record findings.Results: The study included 405 cases with thyroid disorders whose ages ranged from 15 to 71 years old with a mean age of 30.5±10.6 years. Females were 82.7% of the included cases, and 83.8% were Saudi. Thyroid related symptoms were recorded for 1-2 years among 58.1% of the cases and for more than 5 years among 15.8%. Thyroid enlargement was recorded for 73.1% of the cases. The multinodular enlargement was recorded for 53.5% of the cases followed with diffuse thyroid enlargement (27.3%). Regarding the type of surgery undergone, total thyroidectomy was the most recorded followed with lobectomy.Conclusions: The study revealed that the majority of the cases were females at middle age presented with benign lesions with Euthyroid status. The most important conclusion was the significant remarkable underreporting of the different clinical data for the cases with many missing items.