Dietary Supplementation With Cysteine Prevents Adverse Metabolic Outcomes of Repeated Cures With Paracetamol in Old Rats

Br J Nutr. 2017 Dec;118(11):889-896. doi: 10.1017/S0007114517002847. Epub 2017 Nov 27.

Abstract

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

Keywords: 4-hydroxy-acetanilide); APAP paracetamol (acetaminophen; CT control; Cys cysteine; Cys–gly cysteinyl–glycine; Hcy homocysteine GM gastrocnemius; N-acetyl-para-aminophenol; Cysteine; GSH; Liver; Skeletal muscles.

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Cysteine / pharmacology*
  • Dietary Supplements*
  • Glutathione / metabolism
  • Homocysteine / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Rats
  • Rats, Wistar
  • Sarcopenia / drug therapy*

Substances

  • Homocysteine
  • Acetaminophen
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
  • Cysteine