Porphyric enzymes in hamster Harderian gland, a model of damage by porphyrins and their precursors. A chronobiological study on the role of sex differences

The Syrian hamster Harderian gland (HC), representing a highly porphyrogeni c organ. was used as a model system for studying physiologically occurring damage of biomolecules by porphyrins and their precursors. phenomena associ ated with from the pathological situation of porphyrias. The species used e xhibits the peculiarity of much higher porphyrogenesis in females than in m ales. offering possibilities for comparison of effects by different porphyr in levels in one species. Since concentrations of free. and therefore, radi cal-generating porphyric metabolites are difficult to determine in the pres ence of high amounts of secreted and crystallizing porphyrins. which are, m oreover, mainly surface-reactive, and since indications existed fur tempora l changes in the oxidative stress caused by these molecules. the following approach was chosen in HGs of both females and males. activities of the rel evant porphyric enzymes, delta -aminolevulinate synthase (ALA-S), delta -am inolevulinate dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D). we re determined throughout the circadian cycle. Results were compared with th e temporal patterns of lipid peroxidation and protein damage in the same gl ands. In females, a strong correspondence was observed between protein carb onyl and lipid peroxidation, peaking at the end of both photophase and scot ophase: maximal activities of the three porphyric enzymes ALA-S, ALA-D. and PBG-D either coincided or slightly preceded the peaks of oxidative damage. In males, lower enzyme activities, especially in PBG-D, were associated wi th weakly expressed rhythmicity. Correspondingly, lipid peroxidation was lo wer and exhibited a smaller rhythm amplitude; protein carbonyl of males sho wed a temporal pattern differing from that of females, with regard to ampli tude and phasing. These data are in agreement with morphological observatio ns demonstrating particularly severe cell damage in the female HG under nor mal conditions. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.