4.7 Article

Effects of losartan and L-serine in a mouse liver fibrosis model

Journal

LIFE SCIENCES
Volume 278, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119578

Keywords

L-Serine; Losartan; Carbon tetrachloride; Liver fibrosis; Inflammation; Collagen

Funding

  1. National Research Foundation of Korea (NRF) - Korea government (Ministry of Science and ICT) [2017R1E1A1A01072781]
  2. National Research Foundation of Korea [2017R1E1A1A01072781] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The study demonstrates that L-serine can reduce the extent of hepatic fibrosis and holds potential for clinical applications.
Hepatic fibrosis is a common liver disease caused by excessive collagen deposition in the liver. Since liver transplantation is the only current treatment for cirrhosis with worsened fibrosis, a new strategy to develop antifibrosis drugs with no adverse effects is necessary. In recent studies, amino acids have been applied as a type of therapy in various fields. L-serine plays a major role in antioxidant production via the maintenance of nicotinamide adenine dinucleotide phosphate hydride production in the mitochondria. L-serine may reduce fibrotic lesions in a mouse model of chronic liver injury. This study used 27 six-week-old C57BL/6 mice and injected them three times a week for eight weeks with carbon tetrachloride (CCl4) (1.5 mg/kg, 10% v/v CCl4 in olive oil) to create a hepatic fibrosis mouse model. The mice, which weighed approximately 20-30 g, were randomly classified into four groups: 1) the olive oil group, which received intraperitoneal injection of olive oil (1.5 mg/kg, 3 times per week for 8 weeks); 2) the CCl4-only group; 3) the CCl4 + losartan (10 mg/kg, PO, 5 days on, weekend off for 8 weeks) group; and 4) the CCl4 + L-serine (100 g/L, free access for 8 weeks) group. Hematoxylin and eosin staining and Masson's trichrome staining showed reduced inflammatory cell deposition and collagen deposition in the liver tissue in the L-serine supplemented group. L-serine was found to reduce the spread of hepatic fibrosis and has potential use in clinical settings. Based on these histopathological observations, L-serine is a potential anti-fibrosis drug.

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