Tubular Stress Proteins and Nitric Oxide Synthase Expression in Rat Kidney Exposed to Mercuric Chloride and Melatonin

Alessandra Stacchiotti ^1*, Francesca Ricci ¹, Rita Rezzani ¹, Giovanni Li Volti ¹, Elisa Borsani ¹, Antonio Lavazza ¹, Rossella Bianchi ¹ and Luigi Fabrizio Rodella ¹

¹ Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy (AS,FR,RR,GLV,EB,RB,LFR), and Laboratory of Electron Microscopy, Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia-Romagna, Brescia, Italy (AL)

^* To whom correspondence should be addressed. E-mail: stacchio{at}med.unibs.it.

Submitted on January 24, 2006
Accepted on 13 June 2006

	Abstract

Stress proteins, such as HSP70 members (HSP72 and GRP75) and metallothionein (MT), protect the kidney against oxidative damage and harmful metals, whereas inducible nitric oxide (iNOS) regulates tubular functions. A single dose of mercuric chloride (HgCl₂) can cause acute renal failure in rats, its main target being the proximal tubule. Oxidative damage has been proposed as one of its pathogenic mechanisms. Here, we tested whether Melatonin (MEL), a powerful antioxidant compound, is effective against HgCl₂-nephrotoxicity. Rats were treated with saline, HgCl₂ (3.5 mg/kg), MEL (5 mg/kg) and MEL+HgCl₂ and examined after 24h for HSP72, GRP75, MT and iNOS by immunohistochemistry and immunoblotting. The tubular effects of the treatment were then characterized by ultrastructure. In HgCl₂ group, all markers were overexpressed in convoluted proximal tubules and sometimes in distal tubules. In MEL+HgCl₂ group, GRP75 and iNOS decreased in convoluted and straight proximal tubules, whereas HSP72 and MT persisted more than the saline and MEL only groups. Tubular damage and mitochondrial morphometry were improved by MEL pretreatment. In conclusion, the beneficial effect of MEL against HgCl₂-nephrotoxicity was outlined morphologically and by the reduction of the tubular expression of stress proteins and iNOS. These markers could represent sensitive recovery index against mercury damage.

Key Words: mercury, nephrotoxicity, melatonin, stress proteins, nitric oxide synthase

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