Oxidative stress in the pathogenesis of canine zinc-responsive dermatosis

Zinc deficiency causes skin diseases both in humansand in animals. The underlying pathogenic mechanismsremain unclear, but a growing body of evidenceindicates a role for zinc in skin protectionagainst free radical-induced oxidative damage. Theimmunohistochemical expression of heat shock proteins(HSPs; Hsp27, Hsp72, Hsp73 and Hsp90), Cu⁄ Znsuperoxide dismutase (SOD), metallothionein (MT),Ki-67 antigen and active caspase-3 were evaluated innormal canine skin and in samples from eight dogswith zinc-responsive dermatosis. All investigatedHSPs showed intense cytoplasmic immunostainingin the affected epidermis. Focal nuclear positivity ofHsp72 was also detected in keratinocytes. AlthoughCu ⁄ Zn SOD expression was similar to that observedin normal skin, MT immunoreactivity occurred inboth the cytoplasm and the nucleus of basal cells innormal skin but was absent from the affected epidermis.Caspase-3 activation was also absent in theinvolved epidermis, which revealed a high Ki-67index (a 3.5- to 9-fold increase compared with normalskin). These results support the hypothesis that cellularresponse to stress, particularly oxidative stress, isinvolved in the pathogenesis of skin lesions in caninezinc-responsive dermatosis. The lack of MT immunoreactivityin the affected epidermis may be indicativeof low zinc levels, thus resulting in vulnerability tooxidative damage. In contrast, high expression levelsof HSPs in skin during zinc deficiency may conferprotection against a variety of dangerous stimuli,contributing to inhibition of apoptosis and to cellcycle regulation of proliferating keratinocytes.[...