Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.

ABSTRACT:The distribution and the metabolic fate of 4-n-nonylphenol were investigated in male and female Wistar rats dosed orally with 1 g/kg ("low-dose") or 10 mg/kg ("high-dose") labeled 4-n-nonylphenol. Following a 4-day metabolic balance study, neither the distribution pattern nor the residual levels of 4-n-nonylphenol were found to be different between groups, and no unexpected tissuespecific accumulation of 4-n-nonylphenol was detected. Most of the radioactivity was eliminated in urine, and consisted of hydrophilic metabolites very likely resulting from extensive ␤-oxidation of the nonyl side chain and from the conjugation of the phenol to sulfate or to glucuronic acid. Traces of ring-hydroxylated nonylphenol were also characterized. Fecal excretion was mainly associated with unchanged 4-n-nonylphenol and with side chain hydroxylated 4-n-nonylphenol. Experiments carried out in pregnant rats exposed to a low-dose of 4-n-nonylphenol from day 3 to day 19 of gestation demonstrated similar metabolic pathways for this xeno-estrogen. Very limited amounts, if any, of non metabolized 4-n-nonylphenol did reach fetuses. The oxidative metabolism of 4-n-nonylphenol leads to the formation of both ring-hydroxylated and side chain hydroxylated metabolites. The latter metabolic pathway may be a major metabolic pathway for branched 4-nonylphenols and may be a clue to understand their biological activity.