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A simple method for long-term drug infusion in mice: evaluation of guanazole as a model (38488)
Abstract:
A simplified technique for iv infusion in unrestricted DBA/2-J inbred mice has been described. The method, which involves direct cannulation of the tail vein with polyethylene tubing, is suitable for routine use. Guanazole, an antileukemic agent with a short plasma half-life, was evaluated as a model compound. After administration for 47 hr at the rate of 0.3 ml/hr, guanazole (30 mg/ml) caused a marked inhibition of incorporation of 14 C-uridine, administered 15 min before sacrifice, primarily into DNA of spleen, thymus and bone marrow in decreasing order. Inhibition of incorporation into RNA was less marked but followed a similar pattern. The effects on the incorporation of uridine in nucleic acids of kidney, heart and brain were minimal. Increased incorporations into RNA and DNA occurred in liver. The data for the hemopoietic and lymphoid organs, namely spleen, thymus and marrow, are consistent with the reported immunosuppressive and mylelosuppressive effects of the drug and also with the inhibition of ribonucleoside diphosphate reducaste by guanazole.
Insights
A new simplified intravenous infusion technique for mice enables routine drug administration. This study shows guanazole effectively inhibits nucleic acid synthesis in lymphoid organs, indicating its potential as an antileukemic agent.
Area of Science:
- Pharmacology
- Molecular Biology
- Animal Models
Background:
- Intravenous (IV) drug delivery requires precise techniques, especially in small animal models.
- Guanazole is an antileukemic agent with a short plasma half-life, necessitating efficient administration methods.
- Understanding drug effects on nucleic acid synthesis is crucial for evaluating therapeutic efficacy.
Purpose of the Study:
- To describe a simplified IV infusion technique for DBA/2-J mice.
- To evaluate the effects of guanazole on nucleic acid synthesis in various organs.
- To correlate observed effects with guanazole's known pharmacological properties.
Main Methods:
- Developed a simplified IV infusion technique using tail vein cannulation with polyethylene tubing in DBA/2-J mice.
- Administered guanazole (30 mg/ml) at 0.3 ml/hr for 47 hours.
- Measured the incorporation of 14C-uridine into DNA and RNA in spleen, thymus, bone marrow, kidney, heart, and brain post-administration.
Main Results:
- Guanazole markedly inhibited 14C-uridine incorporation into DNA and RNA in spleen, thymus, and bone marrow.
- Minimal effects on uridine incorporation were observed in kidney, heart, and brain.
- Increased incorporation into nucleic acids was noted in the liver.
- Results align with guanazole's known immunosuppressive and myelosuppressive activities.
Conclusions:
- The described IV infusion technique is suitable for routine use in mice.
- Guanazole effectively inhibits nucleic acid synthesis in hemopoietic and lymphoid organs.
- Findings support guanazole's potential as an antileukemic agent and its mechanism involving ribonucleoside diphosphate reductase inhibition.
