Selenium-Alleviated Hepatocyte Necrosis and DNA Damage in Cyclophosphamide-Treated Geese by Mitigating Oxidative Stress

Biol Trace Elem Res. 2020 Feb;193(2):508-516. doi: 10.1007/s12011-019-01717-3. Epub 2019 Apr 25.

Abstract

Selenium (Se) has been well recognized as an immune-enhancing agent with antioxidant and anti-tumor properties. The commonly used chemotherapy drug, cyclophosphamide (CTX), induces liver injury by increasing the reactive oxygen species (ROS) level. However, little is known about how Se alleviates CTX-induced liver injury in geese. In this study, 90 male Magang geese (3 days old) were randomly allocated into three groups (control, CTX, and Se + CTX group) with three replicates per group and ten geese per replicate. The control and CTX groups were fed a basal diet (Se content was 0.03 mg/kg). The Se + CTX group was fed a basal diet containing 0.44 mg/kg sodium selenite (Se content was 0.2 + 0.03 mg/kg). The control group was injected with 0.5 mL saline, while the CTX and Se + CTX groups were injected with CTX at 40 mg/kg body weight per day on days 21-23. The liver index, liver histology, and ultra-micromorphology detected antioxidant enzyme activity in the liver and serum. In addition, we detected the liver marker enzymes and protein levels in serum, and hepatocyte DNA damage. Se could alleviate liver development dysregulation, hepatocyte structural damage, the disturbances in antioxidant enzyme (GPx, CAT, and SOD) activity, and malondialdehyde (MDA) levels in the serum and liver. Besides, Se could alleviate the dysregulation of liver marker enzyme (ALT and AST) activity and protein (ALB and TP) levels in the serum, and DNA migration induced by CTX. In conclusion, Se may inhibit hepatocyte necrosis and DNA damage by inhibiting CTX-induced oxidative stress.

Keywords: Cyclophosphamide; DNA damage; Liver; Oxidative stress; Selenium.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity
  • Catalase / blood
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Cyclophosphamide / toxicity*
  • DNA Damage / drug effects*
  • Geese
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Male
  • Malondialdehyde / blood
  • Malondialdehyde / metabolism
  • Necrosis / prevention & control
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Reactive Oxygen Species / metabolism
  • Selenium / pharmacology*
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / metabolism
  • Trace Elements / pharmacology

Substances

  • Antineoplastic Agents, Alkylating
  • Reactive Oxygen Species
  • Trace Elements
  • Malondialdehyde
  • Cyclophosphamide
  • Catalase
  • Superoxide Dismutase
  • Selenium