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The effect of Met-enkephalin on mice liver lysosomes
V Sverko1, T Marotti, M Gavella
1Department of Experimental Biology and Medicine, Ruder Boskovic Institute, Zagreb, Croatia.
Abstract:
The unsedimentable activities of acid phosphatase (AP) and beta-glucosidase (BG), from mice liver lysosomes significantly increased 6 h after a single i/p injection of Met-enkephalin (MENK). The activity of AP in the serum at the same time remained unchanged. Multiple injections of MENK (8 x 10 mg/kg) induced a significant decrease in AP activity in the serum and no change in the unsedimentable activities of AP or BG. MENK did not elicit any significant extracellular release of lactate dehydrogenase (LDH) either, indicating that, under the experimental conditions described, the cells remained intact. Other parameters, such as the activities of AP and BG in the liver and total sialic acid content in the serum and spleen remained unaltered. Moreover, MENK in concentrations of 10(-12) M, 10(-8) M, 10(-6) M or 10(-4) M did not change the activities of the lysosomal enzyme markers AP or BG in vitro. These data indicate far less pronounced transient effects of MENK on lysosomal membranes and enzymes compared to Leu-enkephalin which may be relevant for the use of MENK in combined chemo-immunotherapy.
Insights
Met-enkephalin (MENK) transiently increased lysosomal enzyme activity in mouse liver after a single injection. Multiple doses, however, decreased serum acid phosphatase, suggesting MENK has limited effects on cell integrity.
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Lysosomal enzymes play crucial roles in cellular processes.
- Met-enkephalin (MENK) is an endogenous opioid peptide with potential therapeutic applications.
- Understanding MENK's effects on cellular components is vital for its clinical use.
Purpose of the Study:
- To investigate the effects of Met-enkephalin (MENK) on lysosomal enzyme activity in mice.
- To determine if MENK impacts cell integrity and extracellular enzyme release.
- To compare MENK's effects with Leu-enkephalin for potential therapeutic relevance.
Main Methods:
- Mice received single or multiple intraperitoneal injections of MENK.
- Assessed unsedimentable acid phosphatase (AP) and beta-glucosidase (BG) activities in liver lysosomes.
- Measured serum AP activity, lactate dehydrogenase (LDH) release, and total sialic acid content.
- Evaluated in vitro effects of MENK on lysosomal enzyme activities.
Main Results:
- A single MENK injection significantly increased lysosomal AP and BG activity at 6 hours.
- Serum AP activity remained unchanged after a single injection but decreased with multiple injections.
- MENK did not induce significant LDH release, indicating preserved cell integrity.
- In vitro MENK exposure did not alter AP or BG enzyme activities.
Conclusions:
- MENK induces transient increases in mouse liver lysosomal enzyme activity after acute administration.
- Chronic MENK administration affects serum AP levels but not lysosomal enzyme activity.
- MENK exhibits limited impact on cell integrity and lysosomal enzyme activity in vitro.
- MENK demonstrates less pronounced effects on lysosomal membranes compared to Leu-enkephalin, relevant for chemo-immunotherapy.