Methotrexate (MTX) is a first-line synthetic antimetabolite agent routinely used to treat some cancers, rheumatoid arthritis, and other chronic autoimmune and inflammatory diseases such as psoriasis. However, among the side effects of this substance, the most serious is hepatotoxicity, which can lead the patient to progressive liver fibrosis and cirrhosis (LERTNAPAWAN; CHONPRASERTSUK; SIRAMOLPIWAT, 2019).

Currently, several drugs are used to prevent the toxic effects of methotrexate. Polyethylene glycol (PEG) is a safe substance with an osmotic laxative effect widely used in medicine and has antioxidant effects. It is an accessible, effective, and low-cost drug whose performance as a preventive agent of hepatotoxicity has already been recorded in the scientific literature.

In an article published in Acta Cirúrgica Brasileira (v. 37, n. 5), scientists from Turkey propose an unprecedented histopathological and biochemical analysis focused on the antifibrotic effect of PEG 3350 to prevent liver damage induced by methotrexate.

The research was carried out in the laboratory of the Center for Research and Application of Experimental Animals at Istanbul Bilim University, using male albino Wistar rats of the same weight and age range. Ten were in a control group, while the other 20 had a methotrexate-induced liver injury. Among these, ten received PEG 3350, and ten had only a saline solution (NaCl) administered peritoneally for two weeks.

Analyzes of liver tissue histopathology showed significantly higher levels of hepatocyte necrosis, fibrosis and cellular infiltration in the saline group compared to PEG-treated individuals. In the latter, the incidence of bridging necrosis, fibrosis and cell infiltration in the portal area was also lower.

The biochemical analysis performed from a blood sample taken by cardiac puncture confirmed that the levels indicative of ALT, TNF-α and TGF-β damage, as well as the plasma levels of MDA, hepatic MDA and pentraxin-3, which indicate oxidative stress, were significantly lower in the group that received PEG compared to the saline group.

Such results, illustrated in the study with figures and tables, allow the authors to conclude that polyethylene glycol is effective in preventing liver damage from toxicity, not only in the case of MTX but also with other substances that cause liver damage by triggering oxidative stress of the organ’s cells.

Thus, although the findings presented are still limited to research with rats, their data increase the knowledge of the effects of PEG in preventing liver toxicity, calling for further studies.

Read more (References)

Lertnawapan R, Chonprasertsuk S, Siramolpiwat S. Association between cumulative methotrexate dose, non-invasive scoring system and hepatic fibrosis detected by Fibroscan in rheumatoid arthritis patients receiving methotrexate. Int J Rheum Dis. 2019;22(2):214-221. https://doi.org/10.1111/1756-185X.13442

Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016;16(Suppl. 6):s104-9. https://doi.org/10.7861/clinmedicine.16-6-s104

To read the article, access:

Acar, Hüseyin et al. Antifibrotic preventive effect of polyethylene glycol (PEG) 3350 in methotrexateinduced hepatoxicity model. Acta Cirúrgica Brasileira [online]. 2022, v. 37, n. 5 [Accessed 23 July 2022] , e370507. Available from: <https://doi.org/10.1590/acb370507>. Epub 22 July 2022. ISSN 1678-2674.

Full article available at: https://doi.org/10.1590/acb370507

Links

Istanbul Bilim University (Demiroğlu Bilim Üniversitesi): https://demiroglu.bilim.edu.tr/

Acta Cirurgica Brasileira – ACB: https://www.scielo.br/j/acb/

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Preclinical and preliminary clinical data strongly suggest that valproic acid (VPA), due to its epigenetic effects, may be an effective drug to combat solid tumors, in combination therapy with classical cytotoxic drugs, with other molecularly targeted drugs or radiation.

In an article published in v. 37, n. 4 of Acta Cirúrgica Brasileira, researchers from the Federal University of Paraná UFPR, in southern Brazil, analyzed the effects of VPA on the skin healing process in a murine model. Sixty male Wistar rats were divided into two groups: the experimental group, treated with VPA (100 mg/kg/day); and the control group, which received only a saline solution, also by gavage.

A median incision of approximately 5 cm was made in the ventral abdominal wall, and the healing of the skin was studied in three moments (third, seventh and 14th day).

The article indicates the parameters, techniques, equipment and procedures used in the research and displays the results in tables. On the third day examination, the inflammatory reaction was either acute or subacute in both groups. On the seventh and 14th days, the inflammatory reaction was chronic in the control group and subacute in the experimental group, which was treated with VPA.

Although the number of leukocytes was higher in the analysis of the cellularity of the histological section of the experimental group on the third day, the difference was not significant for the result of the analysis on the other days. Thus, it appears that initially the inflammatory process was more intense in the group that received VPA.

Regarding angiogenesis, the number of vessels was lower in the experimental group at the three moments. In the three moments of collagen analysis by immunohistochemistry, the density of collagen I was higher in the control group, with the group treated with VPA showing higher density of collagen III. Myofibroblasts appeared rare on the third day and in moderate quantities in the other periods.

The article indicates the parameters, techniques, equipment and procedures used in the research and displays the results in tables. In addition to the results focused on the analysis of the epigenetic effect of VPA, caution is recommended in the application of the treatment, since epigenetic blockade can potentiate the damage eventually caused by chemotherapy or radiotherapy.

Read more

Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med, 6(265):265sr6, 2014. https://doi.org/10.1126/scitranslmed.3009337

To read the full article, access:

Biondo-Simões, Rachel et al. The effects of valproic acid on skin healing: experimental study in rats. Acta Cirúrgica Brasileira [online], v. 37, n. 4, 2022. https://doi.org/10.1590/acb370403

Links

Acta Cirurgica Brasileira – ACB: https://www.scielo.br/j/acb/

Universidade Federal do Paraná – UFPR: http://www.ufpr.br/portalufpr/

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When there is blunt abdominal injury, this function can be severely impaired, making the intestine a gateway for systemic inflammatory processes, which can rapidly progress to multi-organ dysfunction, leading to life-threatening complications.

In this scenario, understanding the pathogenesis of intestinal damage caused by abdominal trauma is essential to a better prognosis.

In the article Potential influences of expression levels of MFGE8 and HMGB1 on the intestinal mucosal barrier function and inflammatory response after blunt abdominal injury in rats published in Acta Cirúrgica Brasileira, vol. 37, n. 3, researchers from the Department of Trauma Surgery at the First Affiliated Hospital of Wenzhou Medical University, China, present their findings from the analysis of the expression of MFGE8 and HMGB1 proteins in the recovery of intestinal injuries caused by abdominal trauma.

Many studies have already proven the benefits of MFGE8 in recovering injured tissues (BU et al., 2007). The results obtained in the presented article converge with the literature, which attributes the therapeutic effects of MFGE8 overexpression to the negative regulatory effect (downregulation) it exerts on the HMGB1 protein. However, this is just one of the interesting reflections of the complex relationship between these proteins.

The work developed by the authors seeks to analyze this dynamic only in the context of a blunt abdominal injury that affects the intestinal mucosal barrier. In the presented scenario, it is demonstrated the attenuation of the inflammatory response and a significant improvement in the recovery of the intestinal barrier, thanks to the intravenous intervention with human recombinant MFGE8, reducing the expressive levels of HMGB1.

With a description of the reagents, equipment and technical procedures performed, the study evaluated the RhoA/ROCK signaling pathway (INOUE et al., 2004) in Sprague Dawley (SD) rats, which were submitted to abdominal contusion. Trauma provoked an inflammatory response in intestinal tissues, with increased serum levels of TNF-α, IL-1β, IL-6 and MDA. Upregulation of HMGB1, RhoA and ROCK2 also occurred while MFGE8 showed downregulation. Such effects and the relief provided by the intervention with rhMFGE8 are demonstrated in the article, including the use of figures and tables.

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Ribeiro AB, Giusti H, Souza APT, Franci CR, Saia RS. Dexamethasone prevents lipopolysaccharide-induced epithelial barrier dysfunction in rat ileum. Shock. 2018;49(3):334-344. https://doi.org/10.1097/SHK.0000000000000930

Bu HF, Zuo XL, Wang X, Ensslin MA, Koti V, Hsueh W, et al. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007;117(12):3673-83. https://doi.org/10.1172/JCI31841

Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med. 2004;10(7):712-718. https://doi.org/10.1038/nm1060

To read the article, access:

Tao, Lijun, Xu, Hongbo and He, Qianggui Potential influences of expression levels of MFGE8 and HMGB1 on the intestinal mucosal barrier function and inflammatory response after blunt abdominal injury in rats. Acta Cirúrgica Brasileira [online], v. 37, n. 3, e370303, 2022. https://doi.org/10.1590/acb370303

Links

The First Affiliated Hospital of Wenzhou Medical University: http://english.wenzhou.gov.cn/art/2018/1/2/art_1231307_14752810.html

Acta Cirúrgica Brasileira – ACB: https://www.scielo.br/j/acb/

O post Downregulation of the high-mobility protein HMGB1 (amphoterin) induced by overexpression of MFGE8 (lactaderin) improves the prognosis of blunt abdominal injury apareceu primeiro em ACTA Cirúrgica Brasileira.

Portal hypertension is a health problem that can lead to serious complications, including death from hemorrhagic shock due to rupture of esophagogastric varices. The high incidence and mortality rates of frontal hypertension in patients admitted with upper gastrointestinal bleeding at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), where the study was carried out, justify this unprecedented study developed by researchers from São Paulo and Rio de Janeiro, in southeastern Brazil.

The article “Experimental model of portal hypertension and esophagogastric varices in minipigs: pressure and endoscopic pilot study”, published by ACTA Cirúrgica Brasileira (v.37 ed 1, 2022) , sought to validate an unprecedented experimental model in br1 mini pigs, using the partial portal vein ligation technique to induce portal hypertension and esophageal varices described by Jensen et. al. in the 80s.

In their study, the researchers observed that the technique – already tested in small to medium-sized animals, from rodents to dogs – is undoubtedly effective in producing portal hypertension, but the formation of esophagogastric varices was not observed in all species. Noting that these different results could be related to differences in the portal system of each species, the authors proposed this experiment with five specimens of br1 mini pigs. The portal systems of humans and pigs are similar at a morphological and microstructural level. The minipig has splenic hemodynamics and hepatic metabolism like humans, providing more accurate results.

After a clear and detailed description of the technical procedure to which the models were submitted – including the compliance of these actions with the current legislation on ethics in animal research – the authors concluded that the animal model obtained is valid for the production of portal hypertension in mini pigs br1, but not in the formation of esophageal varices. Thus, the study suggests a starting point for the development of research in this field with medium-sized animals, and indicates the direction to follow in future experiments to obtain a reproducible and reliable model.

Jensen LS, Krarup N, Larsen JA, Juhl C, Nielsen TH. Effect of acute portal hypertension on hepatosplanchnic hemodynamics and liver function. Scand J Gastroenterol. 1986;22:463-70. https://doi.org/10.3109/00365528609003101

Mariano M. Miniature swine (minipig) in biomedical experimental research: the Minipig br1. Acta Cir Bras. 2003;18(5):387-91.

To read the article, access:

Release for the original article “Experimental model of portal hypertension and esophagogastric varices in minipigs: pressure and endoscopic pilot study” by MALUF FILHO et al. (fauze.maluf@terra.com.br), published in the vol. 37, no. 1 of ACTA Cirúrgica Brasileira, 2022

Check out the full article at: https://doi.org/10.1590/acb370103

Links

Laboratórios de Investigação Médica- LIM/HCFMUSP : https://limhc.fm.usp.br/portal/

MINIPIG Pesquisa e Desenvolvimento LTDA : http://www.minipig.com.br/minipig.asp

Acta Cirúrgica Brasileira – ACB: https://www.scielo.br/j/acb/

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