Role of midkine in cadmium-induced liver, heart and kidney damage.
Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p < 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p < 0.05, p < 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.
Yazihan
Nuray
N
Pathophysiology Department, Faculty of Medicine, Ankara University, Ankara, Turkey. nurayyazihan@yahoo.com
Kocak
Mehtap Kacar
MK
Akcil
Ethem
E
Erdem
Onur
O
Sayal
Ahmet
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019256:Cadmium Chloride / Q000493:pharmacokinetics / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D000078792:Midkine; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D015854:Up-Regulation
D016207:Cytokines; D004785:Environmental Pollutants; D000078792:Midkine; D019256:Cadmium Chloride