Acute toxicity of folic acid in mice

Area of Science:

• Toxicology
• Pharmacology
• Genetics

Background:

• Folic acid (PGA) is essential for numerous biological processes.
• Understanding its toxicity is crucial for safe therapeutic use.
• Inbred mouse strains offer a model for studying genetic influences on drug toxicity.

Purpose of the Study:

• To investigate the toxicity profile of folic acid (PGA) across different inbred mouse strains.
• To characterize the observed toxicological effects and identify target organs.
• To explore potential strain-specific susceptibility to PGA toxicity.

Main Methods:

• Administration of folic acid (PGA) via intraperitoneal (i.p.) route to various inbred mouse strains.
• Determination of LD50 values to quantify acute toxicity.
• Clinical observation for neurological signs such as convulsions, ataxia, and weakness.
• Histopathological examination of tissues, particularly kidneys, for signs of damage.

Main Results:

• Folic acid (PGA) demonstrated a unique toxicity pattern across different mouse strains.
• Neurological symptoms including convulsions, ataxia, and weakness were observed in susceptible strains.
• Histopathological analysis revealed acute renal tubular necrosis in strains S/RVCri, BDF1, DBA/2, and DBA/2fNCri.
• LD50 values varied significantly between strains, indicating differential susceptibility.

Conclusions:

• Folic acid (PGA) possesses a distinct toxicity profile in mice, influenced by genetic background.
• The kidneys are a primary target organ for PGA-induced toxicity, leading to acute tubular necrosis.
• Strain-specific differences in response highlight the importance of genetic factors in xenobiotic metabolism and toxicity.
• Further investigation into the mechanisms underlying strain-dependent PGA toxicity is warranted.