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Side-effects of peptidoglycan monomer (PGM) treatment in mice
V Sverko1, T Marotti, M Gavella
1Department of Experimental Biology and Medicine, Ruder Bosković Institute, Zagreb, Croatia.
Abstract:
The influence of single (4 mg/mouse) and multiple (1 mg/mouse per day for 5 consecutive days) injections of PGM on some hepatic enzymes, lipid peroxide generation in serum and liver, sialic acid concentration in serum and spleen and hepatic lysosomal membrane permeability was investigated. The studies performed showed that a single injection of PGM in vivo changed temporarily the permeability of lysosomal membranes, lipid peroxidation products and sialic acid concentration, and when administered in vitro modulated superoxide anion production and did not affect the activity of lysosomal membrane enzymes. Multiple injections of PGM did not cause significant changes in the examined parameters. Although the metabolic changes were time-limited and from the toxicological point of view, provoked transient effects, the results obtained may be of importance when using PGM in combined chemo-immunotherapy.
Insights
Single injections of PGM temporarily altered lysosomal membrane permeability, lipid peroxidation, and sialic acid levels. Multiple PGM doses showed no significant effects, suggesting transient impacts relevant for chemo-immunotherapy.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Parenteral administration of drugs can induce metabolic and toxicological changes.
- Understanding the impact of PGM on hepatic and systemic parameters is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the effects of single and multiple PGM injections on hepatic enzymes, lipid peroxidation, sialic acid concentration, and lysosomal membrane permeability.
- To assess the toxicological profile of PGM in vivo and in vitro.
Main Methods:
- In vivo studies involved single and multiple injections of PGM (4 mg/mouse and 1 mg/mouse/day for 5 days, respectively).
- In vitro studies assessed PGM's effect on superoxide anion production and lysosomal membrane enzyme activity.
- Measurements included hepatic enzymes, serum and liver lipid peroxides, serum and spleen sialic acid, and hepatic lysosomal membrane permeability.
Main Results:
- A single PGM injection transiently increased lysosomal membrane permeability, lipid peroxidation products, and sialic acid concentration.
- In vitro, PGM modulated superoxide anion production but did not affect lysosomal membrane enzyme activity.
- Multiple PGM injections did not induce significant changes in the evaluated parameters.
Conclusions:
- PGM administration can induce transient metabolic and toxicological effects, particularly after single doses.
- These time-limited effects are important considerations for the use of PGM in combined chemo-immunotherapy protocols.