To obtain definitive information about the mechanisms of
urinary calculus formation and the structural characteristics of the
calculi induced by
biphenyl administration in rats, with a focus on the sex dependency, the constituents of the
urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (ICP), micro Fourier transform infrared spectroscopy (mFT-IR), and ion chromatography (IC), and structural analyses were carried out by microscopy, mFT-IR, and the electron probe microanalyzer (EPMA) method. We attempted to account for the appreciably higher incidence of
calculi in males than in females. mFT-IR analysis revealed that the
biphenyl-induced
urinary calculi in male rats are composed mainly of
potassium 4-hydroxybiphenyl-o-sulfate (4-HBPOSK), whereas the
calculi in female rats are composed mainly of
4-hydroxybiphenyl (4-HBP) and KHSO(4) produced by the hydrolysis of 4-HBPOSK. Observations of photomicrographs and the results of mFT-IR analysis indicated that the
calculi in males have a multilayer structure consisting of alternating layers of 4-HBPOSK and
calcium phosphate, whereas the
calculi in females have no multilayer structure, but open holes in which needle-shaped crystals are present in some places. In view of the results of these analyses, including the EPMA analysis, it appears that
calculus formation in males may involve a series of successive and irreversible reactions, whereas
calculus formation in females may result from a series of reversible reactions, including the hydrolysis of 4-HBPOSK. It was inferred that the series of irreversible reactions involved in
calculus formation in males is relatively more stable than that in the case of females, and thus, a sex difference in the reaction features may be responsible for the observed difference in the incidence of
calculus formation.