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Estrogen-dependent activity of kidney lysosomal proteolytic enzymes
E Radzikowska1, K Janicki, R Maciejewski
1Human Anatomy Department, Medical University of Lublin.
Abstract:
Drug-induced kidney injury is a potential complication of a number of medicaments. The wide-spread use of estrogens in the form of oral contraceptives and in the form of hormonal replacement therapy, has necessitated extensive studies on the biochemical alterations. The following effects of estrogens on kidney are discussed in greater detail with special regard to enzyme induction. The aim of the study was to evaluate the influence of long-term activity estrogens on kidney lysosomal enzymes like cathepsin B, D and L. Female rats were divided randomly into eight experimental groups. Oestradiolum benzoicum was used for the purpose of this study. Estrogens were given i.m. one time per week for 8 weeks in different doses, respectively: E1--0.00075 g/kg b.w., one time per week; E1.1--0.00075 g/kg b.w. every three days; E2--0.0015 g/kg b.w.. one time per week. E2.1--0.0015 g/kg b.w.. every three days; E3--0.03 g/kg b.w.. one time per week; E3.1--0.003 g/kg b.w.. every three days; KO--untreated animals; K1--treated control, rats received oleum pro injection at the dose of 1.2 ml/100 g b.w. The activity of free and bound fractions of lysosomal enzymes, such as cathepsin B, D and L were assayed in kidney homogenates using spectrophotometric methods. Differences between various experimental groups were tested with ANOVA test. The activity of cathepsin B, D and L fractions showed significant changes compared to control groups. The observed changes were not characteristic in all the studied groups. The most important changes referred to the activity of cathepsin B and D. Differences were noted between the enzymes activity in animals treated with the smallest dose of estrogen and that in control groups. It was smaller in group E1 than in groups K0 and K1. The activity of cathepsin B was higher in group E1 than in control groups. There was no correlation between the dose of injected estrogens and the observed lysosomal activity changes. The changes in lysosomal activity were uncharacteristic.
Insights
Long-term estrogen use can alter kidney lysosomal enzymes, including cathepsin B, D, and L. While significant changes were observed, they were uncharacteristic and showed no clear dose-response relationship in female rats.
Area of Science:
- Biochemistry
- Toxicology
- Endocrinology
Background:
- Drug-induced kidney injury is a recognized complication of various medications.
- Widespread use of estrogens in oral contraceptives and hormone replacement therapy necessitates understanding their effects on kidney function.
- Estrogen's impact on kidney biochemical alterations, particularly enzyme induction, requires detailed investigation.
Purpose of the Study:
- To evaluate the influence of long-term estrogen exposure on kidney lysosomal enzymes.
- Specifically assess the activity of cathepsin B, D, and L in female rats following estrogen administration.
Main Methods:
- Female rats were divided into eight groups, including untreated and vehicle-treated controls.
- Oestradiolum benzoicum was administered intramuscularly weekly or every three days for eight weeks at varying doses.
- Activity of free and bound fractions of lysosomal enzymes (cathepsin B, D, L) was measured in kidney homogenates using spectrophotometry.
- Statistical analysis was performed using the ANOVA test.
Main Results:
- Significant changes in the activity of cathepsin B, D, and L fractions were observed compared to control groups.
- The most pronounced changes were noted in the activity of cathepsin B and D.
- Differences in enzyme activity were detected even at the lowest estrogen dose compared to controls.
- No direct correlation was found between the administered estrogen dose and the observed changes in lysosomal enzyme activity.
- The observed alterations in lysosomal activity were generally uncharacteristic.
Conclusions:
- Long-term estrogen administration can induce changes in kidney lysosomal enzyme activity.
- The observed effects on cathepsin B, D, and L are complex and not consistently dose-dependent.
- Further research is needed to fully elucidate the mechanisms and clinical implications of estrogen-induced kidney alterations.
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