Letter to the Editor: Administration of TGF-ß Inhibitor Mitigates Radiation-induced Fibrosis in a Mouse Model

To the Editor,

We read the study by Gans et al. [4] with great interest. In their study, the authors reported that “mice treated with placebo (n = 10) received daily intraperitoneal injections of only a dimethyl sulfoxide vehicle for 8 weeks (10 survived to histologic analysis)” [4]. We would like to further discuss dimethyl sulfoxide (DMSO).

Dimethyl sulfoxide is a widely used solvent for hydrophobic compounds like plant monomers and signaling pathway inhibitors for in vitro and in vivo experiments. Unfortunately, the authors did not offer the dosage, the concentration of DMSO, or whether there were any adverse effects such as weight loss, decreased appetite, or liver or kidney dysfunction [4]. Can DMSO be used as a vehicle for intraperitoneal injection in laboratory animals? [1]

We are in the process of evaluating intraperitoneal injections of DMSO in mice; our preliminary results suggest that daily intraperitoneal injections of 10 mL/kg DMSO at a concentration of 5% for 7 days did not show any adverse effects, but the experiments are ongoing.

Intraperitoneal injection is a common method of drug administration in animal experiments, and the solubility and the accurate injection of the drug into the peritoneal space affects the absorption of the drug [2]. Gad et al. [3] found that mice could tolerate daily intraperitoneal injections of 0.1 mL/kg DMSO at a concentration of 100% for 1 month. However, we have concerns about this [3]. Assuming a mouse weighs 20 g, the dose per mouse is 0.002 mL, and a dose so small is nearly impossible to measure and inject with confidence into the peritoneal space. Additionally, findings from Worthley et al. [5] also call into question the safety of intraperitoneal injections of DMSO in mice. In that study [5], the LD50 of mice intraperitoneally injected with DMSO at concentrations of 25%, 50%, 75%, or 100% was 15.4, 13.3, 11.9, and 10.9 g/kg, respectively [5]. Intraperitoneal injection of DMSO at concentrations exceeding 25% is harmful to mice and would interfere with the experiment results.

We believe that pure DMSO should not be used as a solvent for intraperitoneal injections in experimental animals. Researchers can prepare the storage solutions with as little pure DMSO dissolving drugs as possible, but in doing so, they will need to dilute the DMSO to the appropriate concentrations to ensure animal safety before intraperitoneal injection.