Oxidative stress in the pathogenesis of canine zinc-responsive dermatosis.
Zinc deficiency causes skin diseases both in humans and in animals. The underlying pathogenic mechanisms remain unclear, but a growing body of evidence indicates a role for zinc in skin protection against free radical-induced oxidative damage. The immunohistochemical expression of heat shock proteins (HSPs; Hsp27, Hsp72, Hsp73 and Hsp90), Cu/Zn superoxide dismutase (SOD), metallothionein (MT), Ki-67 antigen and active caspase-3 were evaluated in normal canine skin and in samples from eight dogs with zinc-responsive dermatosis. All investigated HSPs showed intense cytoplasmic immunostaining in the affected epidermis. Focal nuclear positivity of Hsp72 was also detected in keratinocytes. Although Cu/Zn SOD expression was similar to that observed in normal skin, MT immunoreactivity occurred in both the cytoplasm and the nucleus of basal cells in normal skin but was absent from the affected epidermis. Caspase-3 activation was also absent in the involved epidermis, which revealed a high Ki-67 index (a 3.5- to 9-fold increase compared with normal skin). These results support the hypothesis that cellular response to stress, particularly oxidative stress, is involved in the pathogenesis of skin lesions in canine zinc-responsive dermatosis. The lack of MT immunoreactivity in the affected epidermis may be indicative of low zinc levels, thus resulting in vulnerability to oxidative damage. In contrast, high expression levels of HSPs in skin during zinc deficiency may confer protection against a variety of dangerous stimuli, contributing to inhibition of apoptosis and to cell cycle regulation of proliferating keratinocytes.
Romanucci
Mariarita
M
Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
Bongiovanni
Laura
L
Russo
Anita
A
Capuccini
Silvia
S
Mechelli
Luca
L
Ordeix
Laura
L
Della Salda
Leonardo
L
D000818:Animals; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000627:therapeutic use*
D006360:Heat-Shock Proteins; D008668:Metallothionein; D013482:Superoxide Dismutase; D015032:Zinc