Topical CCL3 Is Well-Tolerated and Improves Liver Function in Diabetic Mice: Evidence from a 14-Day Toxicity Study

Area of Science:

• Immunology
• Wound Healing
• Pharmacology

Background:

• Diabetic wounds show impaired immunity, delayed neutrophil recruitment, and increased infection risk, hindering healing.
• CCL3 (macrophage inflammatory protein-1 alpha) is a chemokine involved in immune cell recruitment.

Purpose of the Study:

• To evaluate the safety and efficacy of topical CCL3 in accelerating diabetic wound healing.
• To assess the systemic toxicity of topical CCL3 in diabetic mice.

Main Methods:

• A 14-day acute toxicity study was performed on diabetic mice using topical CCL3 at 1 µg and 10 µg doses.
• Mice were monitored for clinical signs, body weight, and food intake.
• Serum biochemistry and histopathology of major organs were analyzed on day 14.

Main Results:

• Topical CCL3 treatment restored neutrophil influx, reduced bacterial infection by ~99%, and accelerated wound healing in diabetic mice.
• No adverse clinical effects or systemic organ toxicity were observed in CCL3-treated mice.
• CCL3 treatment showed improved ALT levels and reduced hepatic pathology, suggesting hepatoprotective effects and reduced systemic inflammation.

Conclusions:

• Topical CCL3 is well-tolerated in diabetic mice at doses up to 10 times the effective therapeutic concentration.
• These findings support the preclinical development of CCL3 as a novel therapy for diabetic wound care.