The dual-action monophenolic antioxidant TS-13 accelerates hair coat restoration in a mouse model of chemotherapy-induced alopecia

Chemotherapy remains a mainstay in the treatment of malignant neoplasms, and the search for strategies to overcome or mitigate its side effects, including hair loss (CIA, chemotherapy-induced alopecia), remains extremely important. Despite the proven role of oxidative stress in the pathogenesis of CIA, the number of studies on the potential use of antioxidants for its prevention and treatment is limited. The aim of the study was to investigate the effect of the monophenol sodium 3-(3′-tert-butyl-4′-hydroxyphenyl) propylthiosulfonate (TS-13), which possesses direct and indirect antioxidant activity, on hair regrowth in mice modeling CIA.

Material and methods. The study was performed on 30 outbred mice of both sexes, divided into 4 groups. Group 1 animals served as controls (n = 7). Mice in Group 2 received TS-13 in drinking water at a dose of 100 mg/kg body weight starting 14 days before depilation and throughout the experiment (Group “TS-13”, n = 7). CIA was modeled in mice of Group 3 (Group “CIA”, n = 8) and Group 4 (Group “CIA + TS-13”, n = 8). Animals in Group 4 received TS-13 in drinking water throughout the entire experiment. The backs of all animals were shaved, and the treated areas were depilated. On day 9, mice in Groups 3 and 4 received an intraperitoneal injection of cyclophosphamide solution (120 mg/kg body weight). Subsequently, the backs were photographed every other day, and the obtained images were analyzed. On day 51, the animals were euthanized, organs (liver, heart, left kidney, spleen) were extracted and weighed.

Results and discussion. No significant differences in body weight dynamics were observed between the groups during the experiment; only a tendency towards weight loss was detected in males receiving cyclophosphamide on day 17 (p = 0.0662). In mice of the control group and those receiving TS-13 in drinking water, intensive hair growth began on days 11–13 of the experiment, with complete hair regrowth occurring by days 13–15. In animals of the CIA group, the phase of pronounced hair growth was significantly delayed, starting on day 25 and reaching complete regrowth only by day 40. Administration of TS-13 to mice with CIA (Group 4) accelerated the process, although not to the level of the intact control (Group 1, p = 0.015) or the positive control (Group 2, p = 0.002). Rapid hair growth began on day 17, and complete hair regrowth occurred on day 31; the difference compared to Group 3 was statistically significant (p = 0.004).

Conclusions. TS-13 administration accelerates hair regrowth in mice with CIA model, although it does not completely abolish cyclophosphamide’s ability to induce hair loss. We consider the latter a positive outcome, indicating that the substance does not negate the key therapeutic effect of antitumor agents – their antiproliferative action.

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