Effects of Trihalomethanes on Liver Mitochondria

Introduction: Trihalomethanes (THMs), namely dibromochloromethane (DBCM) and bromodichloromethane (BDCM), are disinfection byproducts of chlorinated water. This experiment aimed to evaluate the mitochondrial dysfunction induced by THMs at low levels in a mouse model

Effects of trihalomethanes on liver: a mouse model

Introduction and objectives: Trihalomethanes (THMs) are disinfection byproducts found in chlorinated water. They are associated with cancer of various organs in human populations and experimental animal models. The aim of this study was to evaluate by histopathology the hepatic changes induced by THMs administered at low levels in a mouse model. Materials and methods: All procedures were made in accordance to the European Directive 2010/63/EU. Forty-two ICR male mice were randomly divided into 4 experimental groups: DBCM-exposed (n=11), BDCM-exposed (n=11), methanol-exposed (n=11) and a negative control (n=9). Animals from DBCM, BDCM and methanol-exposed groups received dibromochloromethane (DBCM), bromodichloromethane (BDCM) and methanol, respectively at a concentration of 117µg/Kg, once daily, by gavage, to a total of four administrations. Animals from control group only received water. Animals were sacrificed 4 weeks after DBCM, BDCM and methanol administrations. Blood biochemistry was performed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), albumin (Alb), total protein (TP), creatinine and urea. Hepatic samples were histopathological evaluated using hematoxylin and eosin (H&E), reticulin and Masson’s trichrome methods. Results: During the experimental protocol, 12 animals died and were excluded from the study. Animals exposed to THMs showed high levels of ALT and TB compared with methanol and control groups (p < 0.05). Histopathological analysis did not reveal any hepatic architectural changes. However, animals from the DBCM, BDCM and methanol groups exhibited multifocal inflammatory cell infiltrates, multifocal hepatocellular necrosis and cytoplasmic vacuolar degeneration, most frequently in the DBCM and BDCM-exposed groups. Hepatocellular nuclei exhibited a disperse chromatin pattern and prominent nucleoli in all animals from DBCM, BDCM and methanol-exposed groups. Reticulin and Masson’s trichrome methods showed normal collagen expression patterns in all groups, with no differences between exposed and control animals. Conclusions: The high levels of blood markers of hepatocellular damage (ALT and TB) and the histopathological findings indicate that both THMs, DBCM and BDCM when ingested at low doses exert toxic effects on hepatocytes.FCT [PTDC/DES/114122/2009], European Regional Development Found (COMPETE, FCOMP-01-0124-FEDER-014707/022692) and CI&DETS (PEst-OE/CED/UI4016

Trihalomethanes in liver pathology: Mitochondrial dysfunction and oxidative stress in the mouse

Trihalomethanes (THMs) are disinfection byproducts found in chlorinated water, and are associated with several different kinds of cancer in human populations and experimental animal models. Metabolism of THMs proceeds through enzymes such as GSTT1 and CYP2E1 and gives rise to reactive intermediates, which form the basis for their toxic activities. The aim of this study was to assess the mitochondrial dysfunction caused by THMs at low levels, and the resulting hepatic histological and biochemical changes in the mouse. Male ICR mice were administered with two THMs: dibromochloromethane (DBCM) and bromodichloromethane (BDCM); once daily, by gavage, to a total of four administrations. Animals were sacrificed four weeks after DBCM and BDCM administrations. Blood biochemistry was performed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), albumin (Alb), total protein (TP), creatinine, and urea. Animals exposed to DBCM and BDCM showed elevated ALT and TB levels (p < 0.05) as compared with controls. Histological analysis confirmed the presence of vacuolar degenerescence and a multifocal necrotizing hepatitis in 33% of animals (n = 2). Mitochondrial analysis showed that THMs reduced mitochondrial bioenergetic activity (succinate dehydrogenase (SQR), cytochrome c oxidase (COX), and ATP synthase) and increased oxidative stress (glutathione S-transferase (GST)) in hepatic tissues (p < 0.05). These results add detail to the current understanding of the mechanisms underlying THM-induced toxicity, supporting the role of mitochondrial dysfunction and oxidative stress in liver toxicity caused by DBCM and BDCM. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P &lt; 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety of hospital discharge before return of bowel function after elective colorectal surgery

© 2020 BJS Society Ltd Published by John Wiley & Sons LtdBackground: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P < 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients