Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia - Online version e-ISSN: 1678-2674

Available and affordable, Polyethylene Glycol (PEG) offers antioxidant and preventive effect of Methotrexate (MTX)-induced liver damage

Drug-induced liver injury is a frequent condition, accounting for up to 5% of all cases of liver damage (KATAREY; VELMA, 2016). And it can be fatal if left untreated.

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.

Seis imagens de microscópio lado a lado. Fundo rosa com pequenas manchas brancas e pequenos círculos roxos em cada uma. As images têm diferentes aproximações. Na terceira e na quarta, uma forma roxa mais alongada. Na última, uma forma branca em formato oval.
Figure 1. Liver histolopathology haematoxylin and eosin (20× and 40× magnification). (a and b) Normal liver, central vein (CV) and portal vein (PV); (c and d) methotrexate and saline groups have bridging necrosis, fibrosis and cellular infiltration in portal area (PV) (arrow); (e and f): methotrexate and polyethylene glycol groups have decreased bridging necrosis fibrosis and cellular infiltration in portal area (PV) (arrow).

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.

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

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: <>. Epub 22 July 2022. ISSN 1678-2674.

Full article available at:


Istanbul Bilim University (Demiroğlu Bilim Üniversitesi):

Acta Cirurgica Brasileira – ACB: