Therapeutic Potential of Diosgenin in Amelioration of Carbon Tetrachloride-Induced Murine Liver Injury

Drug Res (Stuttg). 2024 Apr;74(4):156-163. doi: 10.1055/a-2263-1329. Epub 2024 Mar 8.

Abstract

Diosgenin is a sapogenin with antidiabetic, antioxidant, and anti-inflammatory properties. The current study investigated whether diosgenin could ameliorate carbon tetrachloride (CCL4)-induced liver injury. To cause liver injury, CCL4 was injected intraperitoneally twice a week for 8 weeks. Daily oral administration of diosgenin at doses of 20, 40, and 80 mg/kg was started one day before CCL4 injection and continued for 8 weeks. Finally, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also albumin were assessed. Catalase and superoxide dismutase (SOD) activities in addition to glutathione (GSH) and malondialdehyde (MDA) levels were also quantified in the liver homogenate and routine histological evaluation was also conducted. Elevated serum levels of liver enzymes and decreased serum level of albumin caused by CCL4 were significantly restored following diosgenin administration at doses of 40 and 80 mg/kg. Long-term administration of CCL4 increased inflammatory and apoptotic factors such as IL-1β, caspase 3, TNF-α, and IL-6 and decreased SOD and catalase activities as well as GSH level in liver homogenates; while MDA level was increased. Treatment with diosgenin increased SOD and catalase activities and GSH levels in the liver of injured animals. In addition, liver MDA, IL-1β, caspase 3, TNF-α, and IL-6 level or activity decreased by diosgenin treatment. Additionally, diosgenin aptly prevented aberrant liver histological changes. According to obtained results, diosgenin can dose-dependently diminish CCl4-induced liver functional deficits and histological changes in a dose-dependent manner, possibly due to its antioxidant and anti-inflammation properties, and its beneficial effect is comparable to known hepatoprotective agent silymarin.

MeSH terms

  • Alanine Transaminase
  • Albumins / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Carbon Tetrachloride / toxicity
  • Caspase 3
  • Catalase
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / pathology
  • Glutathione
  • Interleukin-6
  • Liver
  • Mice
  • Superoxide Dismutase
  • Tumor Necrosis Factor-alpha

Substances

  • Antioxidants
  • Carbon Tetrachloride
  • Catalase
  • Caspase 3
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Glutathione
  • Anti-Inflammatory Agents
  • Superoxide Dismutase
  • Albumins
  • Alanine Transaminase