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Role of midkine in cadmium-induced liver, heart and kidney damage
Nuray Yazihan1, Mehtap Kacar Kocak, Ethem Akcil
1Pathophysiology Department, Faculty of Medicine, Ankara University, Ankara, Turkey. nurayyazihan@yahoo.com
Abstract:
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.
Insights
Chronic cadmium exposure increases inflammation and apoptosis in rat organs. This study found that midkine (MK) expression also significantly rises in response to cadmium toxicity, suggesting MK
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Cellular Pathology
Background:
- Cadmium (Cd) is a widespread environmental toxin causing tissue toxicity, inflammation, and apoptosis.
- Midkine (MK) exhibits various biological activities, including antiapoptotic functions.
- Previous in vitro studies indicated increased MK expression following Cd exposure.
Purpose of the Study:
- To investigate the relationship between tissue Midkine (MK) levels, tumor necrosis factor-alpha (TNF-α), and apoptosis in a rat model of chronic cadmium toxicity.
Main Methods:
- Male Wistar rats were exposed to 15 ppm Cadmium (Cd) for 8 weeks.
- MK protein and mRNA levels were quantified using ELISA and RT-PCR, respectively.
- Apoptosis was assessed by measuring tissue caspase-3 activity.
- Cadmium accumulation was measured in liver, kidney, and heart tissues.
Main Results:
- Chronic Cd exposure significantly elevated TNF-α and caspase-3 levels, indicating inflammation and apoptosis.
- MK mRNA and protein levels were significantly upregulated in Cd-treated rats across liver, kidney, and heart tissues.
- Apoptosis was most pronounced in the liver, followed by the kidney and heart, correlating with Cd accumulation.
Conclusions:
- Chronic cadmium administration induces significant inflammation and apoptosis in rat liver, kidney, and heart.
- Midkine (MK) expression is upregulated in response to cadmium-induced tissue damage.
- MK appears to be involved in the mechanisms underlying cadmium toxicity, warranting further investigation.