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The influence of dfp, atropine and toxogonine on tryptophan pyrolase activity in mouse liver
Abstract:
It was found that fluorostigmine (DFP) in doses 0-4 mg/kg i.p. reduced significantly tryptophan pyrolase activity in mouse liver homogenates.se liver homogenates 120 and 180 min after the administration of the drug. On the other hand, fluorostigmine administered in doses 0-8 mg/kg i.p. increases the activity of the enzyme studied at 30 and 60 min after the injection. DFP (0.4 mg/kg i.p.) given in combination with atropine (10 mg/kg i.p.) causes a significant increase in enzyme activity determined 30, 60, 120 and 180 min after the administration of the drug. Toxogonine (in doses 5 mg/kg s.c.) given together with DFP (0.4 mg/kg i.p.) intensifies the activity of tryplophan pyrolase at 180 min after their administration. Simultaneous treatment with toxogonine (5 mg/kg s.c.), atropine (10 mg/kg i.p.) and DFP (0.4 MG/KG I.P.) reduced significantly the activity of the enzyme studied at all time of determination. Moreover, the experiment in vitro showed that DFP in concentrations of 4x10(-9) M; 8X10(-9) M; 1.6X10(-8) M and 3.2x10(-8) M increased tryptophan pyrolase activity in mouse liver homogenates.
Insights
Fluorostigmine (DFP) affects mouse liver tryptophan pyrolase activity, with low doses inhibiting and higher doses activating the enzyme. Combinations with atropine and toxogonine show varied effects on enzyme activity.
Area of Science:
- Biochemistry
- Pharmacology
- Enzymology
Background:
- Tryptophan pyrolase is a key enzyme in tryptophan metabolism.
- Organophosphates like fluorostigmine (DFP) are known enzyme inhibitors.
- Understanding DFP's effect on tryptophan pyrolase is crucial for its toxicological profile.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of fluorostigmine (DFP) on mouse liver tryptophan pyrolase activity.
- To evaluate the influence of co-administration with atropine and toxogonine on DFP's effect.
- To determine the dose-dependent and time-dependent responses of tryptophan pyrolase to DFP.
Main Methods:
- In vivo studies involving intraperitoneal (i.p.) and subcutaneous (s.c.) administration of DFP, atropine, and toxogonine to mice.
- Measurement of tryptophan pyrolase activity in mouse liver homogenates at various time points post-administration.
- In vitro experiments assessing the direct effect of DFP on enzyme activity in liver homogenates at different concentrations.
Main Results:
- DFP (0-4 mg/kg i.p.) significantly reduced tryptophan pyrolase activity at 120 and 180 minutes.
- DFP (0.8 mg/kg i.p.) increased enzyme activity at 30 and 60 minutes.
- Co-administration of DFP with atropine increased activity, while simultaneous treatment with DFP, atropine, and toxogonine decreased it.
- In vitro, DFP increased tryptophan pyrolase activity across tested concentrations (4x10(-9) M to 3.2x10(-8) M).
Conclusions:
- DFP exhibits biphasic effects on mouse liver tryptophan pyrolase activity, depending on dose and time.
- Atropine and toxogonine modulate DFP's impact on enzyme activity, with combined administration showing complex interactions.
- The in vitro results suggest a direct activating effect of DFP on tryptophan pyrolase at specific concentrations.