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We examined the correlation between histopathological changes and porphyrin levels in the Harderian glands of male rats after treatment with atropine sulfate. After a single administration of atropine sulfate (250 mg/kg/day), the porphyrin levels in the Harderian glands gradually increased, beginning from 2 hr after administration, and at 36 hr reached a maximum level, which was about 7 times higher than that of the control animals. Histopathologically, the Harderian glands showed marked luminal dilatation and a brownish pigment accumulation in the lumina 6 hr after a single dose. Under daily repeated administrations of atropine sulfate (250 mg/kg/day), the highest porphyrin levels in the Harderian glands were observed 24 hr after the third dose, and were about 9 times higher than those of the control animals. However, beginning from one week after the initial dose, much lower peak porphyrin levels were observed 6 hr after each dose. The maximum porphyrin levels were only twice as high as those of the control animals, and they returned to the control levels 24 hr after each atropine dose. Histological examinations of the Harderian glands revealed that repeated administrations of atropine sulfate induced the same histopathological changes observed after a single atropine administration, and that no aggravated dilation of the lumina or pigmentation in the lumina appeared after such repeated administrations. The degree and incidence of the histopathological changes observed correlated well with the porphyrin levels. Some animals showed a degeneration of the glandular epithelium after 4 weeks of treatment, and the frequency increased slightly after 13 weeks of treatment. The present study suggests that atropine suppresses the expulsion of secretory materials, including porphyrin, from the glandular lumen of the Harderian glands, and thereafter an excessive accumulation of porphyrin induces luminal dilatation. These changes were gradually reduced by repeated administrations. The degeneration of the glandular epithelium after repeated administration might be a consequence of retention of an excessive accumulation of porphyrin.

Effects of atropine sulfate on rat harderian glands. Correlation between morphological changes and porphyrin levels.