A paclitaxel-induced rat model of chemotherapy-induced alopecia

Chemotherapy-induced alopecia (CIA) is one of the most visible and distressing toxicities of cancer therapy, disproportionately affecting women with breast and ovarian cancers, where paclitaxel remains a cornerstone treatment. Despite its widespread use, no standardized animal model exists to study paclitaxel-induced alopecia or evaluate protective strategies. Here, we report the first reproducible rat model of paclitaxel-induced alopecia. Fourteen-day-old Sprague-Dawley rats were randomized to control (n = 20), low-dose paclitaxel (n = 10), or high-dose paclitaxel (n = 10), administered subcutaneously for three consecutive days. Animals were monitored daily, with peak alopecia observed after two weeks. Alopecia severity was graded by blinded assessors using a quintile grading scale (0 = no hair loss, 4 = complete alopecia). Safety endpoints (weight, grooming, activity) were recorded. On day 28, animals were euthanized and a representative biopsy from each group was acquired, formalin-fixed, paraffin-embedded, and stained with H&E. Alopecia severity differed significantly across treatment groups (p < 0.0001, Kruskal-Wallis). Median alopecia scores were 3 in controls, 1 in low-dose paclitaxel (p = 0.0015, Dunn's post hoc), and 1 in high-dose paclitaxel (p < 0.0001), with no significant difference between paclitaxel doses. Dermoscopy demonstrated localized alopecia at the medial rump injection site. Histopathology revealed reduced follicular density and follicular miniaturization, consistent with classical CIA. Paclitaxel administration reliably induced localized alopecia replicating key clinical and histologic features of CIA. This represents the first standardized paclitaxel rat model of CIA and addresses a critical gap in preclinical dermatology and oncology research. This model provides a biologically relevant platform for mechanistic studies and therapeutic testing, particularly relevant to women, for whom alopecia carries substantial psychosocial burden and may influence treatment adherence.