Propane 1, 2-diol (propylene glycol): A new phlogistic agent in miceKala M Mogre1, SR Amladi1, PD Soman2, UK Sheth1
1 Department of Pharmacology, Seth G. S. Medical College, Parel, Bombay-400012, India
2 Radiopharmaceutical Division, Bhabha Atomic Research Centre, Bombay, India
Propane 1, 2-diol (CH 3 -CHOH. CH 2 OH mol. wt. 76.10), a low molecular weight substance produced well defined inflammatory edema in hind paw of mice. Edema was concentration dependent. Submaximal edema occurred with 50% propylene glycol. Hydrocortisone, aspirin, phenylbutazone, indomethacin given orally were significantly effective against this edema. There was also an increase in the capillary permeability with propylene glycol edema. Lack of effect of chlorpheniramine, cyproheptadine and polymyxin B on edema suggest that histamine and serotonin are not involved in the mechnism of propylene glycol edema.
Propane 1, 2-diol (CH 3 -CHOH. CH 2 OH., mol. wt. 76.10), propylene glycol was found to possess prostaglandin-like activity when tested against heat induced protein denaturation (unpublished observation). Since prostaglandins have been claimed to be involved in inflammatory processes,  it was thought worthwhile to investigate if propylene glycol had any phlogistic activity in mice, and to study response to various known anti-inflammatory agents.
Hind Paw Edema
White mice of either sex, weighing between 20-30 gms, were used. Each group consisted of 10 mice.
(a) Extent of edema:
The left hind paw was injected subcutaneously in the plantar pedis with 0.1 ml of 50% concentration of propylene glycol in normal saline. Two hours later the mice were sacrificed with ether and both paws were amputated at tarsotibial joint and weighed on torsion balance. Difference in the weight of two paws was taken as the weight of the edema.
(b) Dose-effect relationship:
The edema was produced with 10, 25, 50 and 100% concentration of propylene elvcol.
(c) Time-course of edema:
This was studied with 50% concentration of propylene glycol.
(d) Effect of anti-inflammatory drugs:
The effect of hydrocortisone, aspirin, phenylbutazone and indomethacin was studied against propylene glycol edema. Drugs were given orally one hour before the injection of propylene glycol.
(e) Effect on capillary permeability:
To observe the increase in capillary permeability involved in acute inflammatory process,  intravenous injection of 0.1 ml of 0.5% concentration of Evans blue More Details was given and extravasation of the dye was observed in edematous paw.
(f) Role of chemical mediators:
In order to elucidate the role of probable mediators alleged in increasing capillary permeability,  the following compounds were tested.
(i) Chlorpheniramine maleate, 5 mg/ kg, orally one hour before the injection of propylene glycol.
(ii) Polymyxin-B, 5 mg/kg, intraperitoneally for three consecutive days.
(iii) Cyproheptadine, 5 mg/kg, orally one hour before the injection of propylene glycol.
Propylene glycol was found to induce edema in mouse hind paw. Edema was concentration dependent. Submaximal edema occurred with 50% concentration [Figure 1],[Figure 2]. Time course of edema suggests that peak edema occurred at 2 hours. R 50 (Period of 50% recovery in Hydrocortisone, aspirin, phenylbutazone and indomethacin given orally were significantly effective against propylene glycol edema. The maximum inhibition of edema occurred with hydrocortisone, 100 mg/kg, aspirin 400 mg/kg, phenylbutazone 200 mg/kg and indomethacin 25 mg/kg [Table 1].
The extravasation of Evans Blue in edematous paw indicated increase in capillary permeability with propylene glycol edema. Chlorpheniramine (antihistamine); polymyxin B (histamine, 5-HT depleter) and Cyproheptadine did not affect the edema [Table 2].
Propylene glycol produced well defined inflammatory edema in mice. Optimum edema was produced with 50% concentration of propylene glycol. Peak edema occurred at 2 hour. R 50 was 30 hours; complete recovery occurred after 10 days. There was increase in the capillary permeability in propylene glycol edema but lack of effect of chlorpheniramine, cyprolheptadine and polymyxin-B suggests that histamine and serotonin are not involved in the mechanism of increase in capillary permeability. Hydro cortisone, aspirin, phenylbutazone and indomethacin were significantly effective in inhibiting the edema but the doses required to suppress the edema are larger than those to suppress carageenin edema. (our unpublished observations). It was our objective to replace carrageenin which needs to be imported for experimental studies by a new phlogistic agent and propylene glycol may serve the purpose provided one keeps into account that doses of standard anti-inflammatory agents required to suppress the edema are proportionately much larger.
[Figure 1], [Figure 2]
[Table 1], [Table 2]