Effects of the circadian mutation 'tau' on the Harderian glands of Syrian hamsters

The Syrian hamster Harderian gland (HG) is an organ continually exposed to oxidative stress caused by high concentrations of porphyric metabolites. Ac cording to previous studies, melatonin, which is rhythmically secreted by t he pineal gland and tonically produced by the HG, antagonizes the oxidative damage. HGs exhibit a strong gender-dependent correlation between porphyri ns, melatonin, and histological appearance. In HGs of both sexes, we have i nvestigated effects of a single gene defect in the circadian clock system ( tau mutation) causing a shortened free-running period and an advanced maxim um of circulating melatonin. Comparisons were made with wild-type animals, one group of which received daily pharmacological injections of melatonin i n late photophase. Changes were observed in histological characteristics, p orphyrin content, antioxidant enzyme activities, and damage of proteins and lipids. HGs of tau hamsters showed morphological changes which can be part ially interpreted in terms of increased damage. Additionally, tau females e xhibited a many-fold augmentation in the percentage of so-called type II ce lls, which are otherwise typical for the male glands. In tau hamsters of bo th sexes, major antioxidative enzyme activities (superoxide dismutase, glut athione reductase, and catalase) were markedly enhanced, a presumably compe nsatory response to increased oxidative stress. Higher oxidative damage in tau HGs was directly demonstrable by a many-fold increase in protein carbon yl. Rises in antioxidative enzymes were also observed upon injections of me latonin; this was, however, not accompanied by changes in protein carbonyl, so that enzyme inductions by the hormone should be understood as protectiv e actions. Our data are not only in accordance with findings on protective effects by melatonin, but also with our earlier observation made in Drosoph ila that perturbations in the circadian system lead to increased oxidative stress. J. Cell. Biochem. 83: 426-434, 2001. (C) 2001 Wiley-Liss, Inc.