Repeated cures with paracetamol worsen sarcopenia in old rats with suboptimal food intake.

The availability of all amino acids is of prime importance to prevent the ageing-associated decrease in skeletal muscle mass i.e. sarcopenia. Cysteine is the precursor of sulfate and glutathione that are both utilized in the liver to detoxify paracetamol (APAP). Cysteine availability could become limiting under repeated cures with APAP, especially when food intake is suboptimal. The aim of the study was to determine whether repeated cures with APAP could worsen sarcopenia. Twenty-two-month-old male Wistar rats received 3 two-week-long cures of APAP (1% of the diet) intercalated with washout periods of two weeks (APAP group). They were compared to untreated control rats euthanatized prior to the experiment (CT group) and rats pair-fed to the APAP group (PF group). Skeletal muscle mass and protein metabolism, as well as plasma amino acids and glutathione were assessed at the end of the third cure. APAP cures reduced food intake by 33, 23 and 33 % during the successive cures leading to an overall body weight loss of 8%. APAP rats lost lean mass during the experiment (-11%). This loss tended (P = 0.09) to be higher than in the PF group (-9%). The mass of hind limb muscles and the absolute synthesis rate of muscle proteins were 13 and 17% lower in the APAP group than the PF group, respectively. Plasma free cyst(e)ine (i.e. all free forms of cysteine not bound to proteins) and glutathione were 25% lower in the APAP group than the PF group. Repeated cures with APAP worsened sarcopenia in old rats with suboptimal food intake likely as a consequence of the APAP-induced shortage in cysteine/glutathione. Clinical studies are needed to clarify the effect of repeated treatments with paracetamol on skeletal muscle mass in older persons having suboptimal or insufficient dietary intakes.