Role of midkine in cadmium-induced liver, heart and kidney damage

Abstract

<jats:p> 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 &lt; 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p &lt; 0.05, p &lt; 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. </jats:p>

Chronic cadmium toxicity induces midkine and galectin-3 production in rat testis

“…In the same study they showed that cytokine secretion was also lower in midkine deficient mice [8]. We previously reported that heart, liver and kidney tissue midkine levels increase in Cd toxicity [10]. This part of our study showed that Cd toxicity induces midkine secretion also in testis tissue.…”

“…It was shown that midkine expression was upregulated in a marine gastropod limpet patella caerulea after they were exposed to sublethal doses of Cd [9]. We previously showed that midkine expression increases in different organ systems of the body in Cd toxicity [10].…”

“…Latest studies have shown that galeetin-3 also takes part in the mechanism of the ischemia induced damages [14]. It behaves as an inflammatory substance like midkine and its level increases in heart tissue after Cd toxicity [10]. Roles of galectin-3 and midkine during Cd toxicity have not been reported in testis tissue yet.…”

Inhibition of DNA methylation attenuates low‐dose cadmium‐induced cardiac contractile and intracellular Ca2+ anomalies

“…For instance, TNF-α is a common marker in the heart in response to stress such as cadmium. 47 An increase in TNF-α may play an important role in cadmium-induced DNA methylation as TNF-α may decrease the SERCA2a RNA and protein levels in the heart with an increased methylation in the SERCA2a promoter region, both of which were attenuated by 5-AZA. In addition, TNF-α may upregulate the expression of MeTase 1 in the heart.…”

Antagonistic effects of selenium against necroptosis injury via adiponectin-necrotic pathway induced by cadmium in heart of chicken

“…[3][4][5][6] In addition, Cd-induced disruption of the blood-testis barrier, testicular damage, germ cell impairment, cardiomyopathy, renal failure, hypertension, arteriosclerotic heart disease 6 and immunosuppression in organs including the heart were reported in mice. 7,8 Furthermore, a signicant decrease of cell viability and Cd cytotoxicity to chicken hepatocytes were observed in the cells treated with Cd.…”