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

Life Sci. 2021 Aug 1:278:119578. doi: 10.1016/j.lfs.2021.119578. Epub 2021 May 6.

Abstract

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 anti-fibrosis 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.

Keywords: Carbon tetrachloride; Collagen; Inflammation; Liver fibrosis; Losartan; l-Serine.

MeSH terms

  • Animals
  • Body Weight
  • Carbon Tetrachloride / chemistry
  • Collagen / chemistry
  • Disease Models, Animal
  • Inflammation
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis, Experimental / metabolism
  • Losartan / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reactive Oxygen Species
  • Serine / pharmacology*

Substances

  • Reactive Oxygen Species
  • Serine
  • Collagen
  • Carbon Tetrachloride
  • Losartan