Effect of intra-arterial cisplatin on dorsal hoof wall tissue of isolated perfused equine limbs

Abstract

Equine hoof canker is a chronic proliferative condition of the hoof tissues that is often time-consuming and frustrating to treat. After surgical debridement, topical application of cisplatin (cis-Diamindichlorplatin II) has been reported, requiring repeatedly handling this hazardous substance during bandage changes. Alternatively, intraarterial application of cisplatin could be used, similar to the treatment of some human neoplastic diseases. As the side effects of such a treatment are currently unknown, evaluation of associated risks is necessary before treating live horses. Thus, forelimbs of thirteen horses underwent an eight-hour perfusion protocol; nine limbs received a 20-minute intraarterial cisplatin infusion (14 mg/600 ml autologous blood-plasma perfusate). Post-treatment, dorsal hoof wall samples were subjected to histological (hematoxylin and eosin) and immunohistochemical (laminin, Ki-67) analysis. Comparisons were carried out using a linear mixed model analysis to investigate the effect of cisplatin. Appearance of primary and secondary epidermal lamellae was not significantly affected by the cisplatin treatment. Notable basal membrane damage was evidenced by significantly weaker laminin staining intensity in the limbs of the cisplatin group than in the control group (p = 0.005). Cisplatin samples showed 54 % weak, 37 % moderate and 9 % strong staining intensities, and control samples showed 12 % weak, 53 % moderate and 35 % strong staining intensities. Median numbers of Ki-67 positive basal cells in the primary epidermal lamellae were not affected by cisplatin. Specifically, even short-term cisplatin exposure significantly compromises the basal membrane of the dorsal hoof wall creating a considerable risk of laminitis.