An evaluation of methods to decrease the availability of inorganic sulphate for sulphate conjugation in the rat in vivo

The concentration of inorganic sulphate in serum of the rat (about 0.9 mM) could be lowered in the following three different ways. (1) Oral administration of sodium chloride (8 mmol/kg) decreased serum sulphate within 2 hr to 0.5 mM. Eight hours after administration serum sulphate had returned to the control level. (2) Feeding of a low-protein diet (8 per cent casein, without supplements of sulphur-containing amino acids or inorganic sulphate salts) reduced urinary sulphate excretion in 2 days to 10 per cent of control. Concomitantly, serum sulphate was decreased to half the control level. (3) Paracetamol (1.0 or 1.5 mmol/kg, orally), a substrate of sulphation, reduced serum sulphate within 3 hr to 30 per cent of control. Eight hours after administration the sulphate concentration tended to rise again. Fasting initially increased serum sulphate; after 3 days of fasting still considerable amounts of inorganic sulphate were excreted in urine (50–70 per cent of control). Even after 3 days serum sulphate was not yet significantly decreased below control. Lowering of the serum sulphate concentration results in a decreased availability of inorganic sulphate.Sulphation of a high dose of phenol (266 μmol/kg) was decreased at a serum concentration of sulphate of 0.3 mM, presumably because sulphate was depleted by the high dose of phenol. Feeding the low-protein diet, however, caused no decrease in sulphation at a tracer dose of [¹⁴C]-phenol (1.25 μmol/kg), while paracetamol pretreatment did cause a decrease in the fraction of the dose that became sulphated, probably because remaining unconjugated paracetamol competed with phenol for sulphation; the tracer dose of [¹⁴C]-phenol did not further deplete sulphate. The findings are discussed in relation to implications for the toxicity of many xenobiotics that are eliminated as sulphate conjugates.