Effects of acetylsalicylic acid, paracetamol and caffeine and a combination of these substances on kidney glutathione levels.

Following preliminary tests in which rats proved to be fairly insensitive to the depletory effect of paracetamol (CAS 103-90-2) on kidney glutathione levels, old male mice from a strain exhibiting particular susceptibility to paracetamol were investigated in respect of the comparative effects of paracetamol, acetylsalicylic acid (CAS 50-78-2, ASA) and caffeine (CAS 58-08-2), and a combination of these substances, on kidney glutathione levels. Additionally, the effects of paracetamol and ASA on hepatic glutathione in mice were also measured. When administered separately at oral doses of 150-600 mg/kg both paracetamol and ASA produced dose- and time-dependent depletion of kidney glutathione concentrations in the mice. The effect of ASA at a given dose was weaker than that of paracetamol. Caffeine showed only a very weak and transient depletory effect up to an oral dose of 60 mg/kg. The effects of the combined administration of paracetamol and ASA on kidney glutathione levels were only additive in nature. The administration of caffeine did not increase the reduction in kidney glutathione levels produced by the combination of paracetamol and ASA. The reduction in hepatic glutathione induced in the mice by paracetamol was considerably more pronounced than that observed in the kidneys. ASA, on the other hand, did not affect glutathione in the mouse liver at those doses which had led to a reduction in kidney glutathione levels.