Alpha-Lipoic Acid Attenuates Fibrotic and Inflammatory Dermal Remodelling in a Bleomycin-Induced Skin Model

Bleomycin (BLM) is a widely used chemotherapeutic agent associated with cutaneous toxicity characterised by inflammation, oxidative stress, and progressive fibrosis. However, effective strategies to mitigate these adverse tissue responses remain limited. This study aimed to evaluate potential protective effects of alpha-lipoic acid (ALA) against the BLM-induced skin model, focusing on fibrotic, inflammatory, and proliferative alterations. Thirty adult Wistar albino rats were randomly assigned to four groups: Control, ALA, BLM, and BLM + ALA. BLM (30 mg/m²) was administered intramuscularly on Days 1, 8, and 15, whereas ALA (50 mg/kg/day, subcutaneously) was administered once daily from Days 1-14. Skin tissues were collected immediately after the final scheduled treatment on Day 15 for histopathological and immunohistochemical analyses. Histopathological evaluation was performed using H&E, Masson's trichrome, and Toluidine blue staining. Immunohistochemical staining was conducted to evaluate the expression levels of collagen types I and III, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), caspase-1, and the proliferation marker Ki-67, followed by quantitative image analysis. BLM exposure resulted in marked epidermal thickening, inflammatory cell infiltration, increased collagen deposition, and elevated mast cell density compared with controls. These histopathological alterations were significantly attenuated in the BLM + ALA group. Consistently, BLM significantly increased the expression of collagen I/III, IL-6, iNOS, caspase-1, and Ki-67, whereas ALA treatment significantly reduced these elevations. Overall, ALA attenuated BLM-induced dermal alterations. ALA treatment was associated with reduced collagen deposition and decreased IL-6, iNOS, caspase-1, and Ki-67 immunoreactivity in the experimental skin model. Further mechanistic studies are required to establish the causal relationships underlying these observations.