Induction by perfluorooctanoic acid of microsomal 1-acylglycerophosphocholine acyltransferase in rat kidney. Sex-related difference.

Response of rat kidney to the challenges by perfluorooctanoic acid (PFOA) was studied using microsomal 1-acyglycerophosphocholine (1-acyl-GPC) acyltransferase as a parameter. Marked induction of the enzyme was brought about in kidney of male rats, whereas the induction in kidney of female rats was far less pronounced. The sex-related difference in the response of kidney to PFOA was much more marked than those seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethy-lenedithio)diethanol (tiadenol). Hormonal manipulations revealed that the sex-related difference in the response of kidney to PFOA was strongly dependent on the state of gonadal hormones of rats. Even after a prolonged administration of PFOA for up to 26 weeks, this sex-related difference was still evident. Induction of peroxisomal beta-oxidation was brought about concurrently with microsomal 1-acyl-GPC acyltransferase and a high correlation was confirmed between the inductions of these two parameters.

Effects of chronic administration of perfluorooctanoic acid on fatty acid metabolism in rat liver: relationship among stearoyl-coenzyme A desaturase, 1-acylglycerophosphocholine acyltransferase, and acyl composition of microsomal phosphatidylcholine.

Male and female rats were fed on a diet containing 0.01% (w/w) perfluorooctanoic acid (PFOA) for 2, 22, or 26 weeks and effect of PFOA on activities of microsomal 1-acylglycerophosphocholine acyltransferase, microsomal stearoyl-coenzyme A (CoA) desaturase, peroxisomal beta-oxidation and on acyl composition of microsomal phosphatidylcholine in liver were studied. The treatment of male rats with PFOA for 2 weeks caused increases in the activities of stearoyl-CoA desaturase, 1-acylglycerophosphocholine acyltransferase, and peroxisomal beta-oxidation. The elevated activities of microsomal 1-acylglycerophosphocholine acyltransferase and peroxisomal beta-oxidation were unchanging throughout the long-term treatment. The induced activity of microsomal 1-acylglycerophosphocholine acyltransferase was found to be highly correlated with the induced activity of peroxisomal beta-oxidation. In contrast to these two enzymes, the increased activity of stearoyl-CoA desaturase by the short-term treatment of rats with PFOA did not last for 26 weeks, although the activity in rats treated for the long-term was higher than that of age-matched controls. The treatment of male rats with PFOA caused great alterations in the acyl composition of microsomal phosphatidylcholine. The high correlation seen between proportion of 18:1 in the C-2 position of phosphatidylcholine and activities of both stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase suggest that these two enzymes participate actively in the regulation of acyl composition of phosphatidylcholine in rat liver. The present results show that hepatic responses to PFOA remain consistent throughout the period of the administration, but the elevated activities of the hepatic enzymes and the altered acyl composition of microsomal phosphatidylcholine returned to control levels within 4 weeks after PFOA was withdrawn from the diet. Even after the chronic administration of PFOA, these parameters of female rats responded only slightly to the challenges by the chemical, which indicates a marked sex-related difference being still apparent in the response of rat liver to PFOA.

Isolation of urinary p-hydroxylated metabolites of mephentermine and phentermine in male Wistar rats.

1. p-Hydroxymephentermine (p-hydroxy-MP) and p-hydroxyphentermine (p-hydroxy-Ph) were isolated as hydrochlorides from urine of male Wistar rats repeatedly dosed with mephentermine (MP). In addition, p-hydroxy-Ph was isolated as the hydrochloride from urine of the rats dosed with phentermine (Ph). 2. These results substantiate previous indications that p-hydroxylation of MP and Ph was a primary metabolic reaction in the rat.

Sex-related differences in the enhancing effects of perfluoro-octanoic acid on stearoyl-CoA desaturase and its influence on the acyl composition of phospholipid in rat liver. Comparison with clofibric acid and tiadenol.

The effects of the peroxisome proliferators clofibric acid (p-chlorophenoxyisobutyric acid), tiadenol [2,2'-(decamethylenedithio)diethanol] and perfluoro-octanoic acid (PFOA) on hepatic stearoyl-CoA desaturation in male and female rats were compared. Treatment of male rats with the three peroxisome proliferators increased markedly the activity of stearoyl-CoA desaturase. Administration of clofibric acid or tiadenol to female rats increased greatly the hepatic activity of stearoyl-CoA desaturase, the extent of the increases being slightly less pronounced than those of male rats. In contrast with the other two peroxisome proliferators, however, PFOA did not change the activity of stearoyl-CoA desaturase in female rats. Hormonal manipulations revealed that this sex-related difference in the effect of PFOA on stearoyl-CoA desaturase activity is strongly dependent on testosterone. The increase in stearoyl-CoA desaturase activity by peroxisome proliferators was not accompanied by any notable increases in the microsomal content of cytochrome b5 or the activity of NADH: cytochrome b5 reductase. The administration of the peroxisome proliferators greatly altered the acyl composition of hepatic phosphatidylcholine and phosphatidylethanolamine (namely the proportions of C18:1 and C20:3,n-9 fatty acids increased in both phospholipids), and the alterations were partially associated with the increase in stearoyl-CoA desaturase activity.

Sex-related difference in the inductions by perfluoro-octanoic acid of peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver.

Inductions by perfluoro-octanoic acid (PFOA) of hepatomegaly, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase were compared in liver between male and female rats. Marked inductions of these four parameters were seen concurrently in liver of male rats, whereas the inductions in liver of female rats were far less pronounced. The sex-related difference in the response of rat liver to PFOA was much more marked than that seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethylenedithio)diethanol (tiadenol). Hormonal manipulations revealed that this sex-related difference in the inductions is strongly dependent on sex hormones, namely that testosterone is necessary for the inductions, whereas oestradiol prevented the inductions by PFOA.