Background:

Accumulation of the wide spread environmental toxin cadmium in tissues results in toxicity. Cadmium (Cd) exposure induces inflammation and apoptosis in the effected tissue. It is shown that, all mRNAs of various genes, which are known to be upregulated by HIF-1 activation under hypoxia, were suppressed by Cd in a dose-dependent manner in hypoxic Hep3B cells.

Aim:

The present study was focused to evaluate the hypoxia inducible factor-1 (HIF-1) mRNA expression in kidney in a chronic Cd toxicity model and their relationships between tissue inflammation stage , apoptosis.

Methods:

Male Wistar rats were exposed to Cd at the dose of 15 ppm for 8 weeks. TNF-a, IL-6 levels were measured by ELISA in renal tissue. Apoptosis was evaluated with tissue caspase-3 levels. HIF-1 mRNA expressions were analyzed by RT-PCR.

Results:

A significant increase in caspase-3, TNF-a, IL-6 tissue levels was seen after Cd toxicity (p<0.001), this was accompanied with a significant decrease in the HIF-1 mRNA expressions. Chronic Cd administration significantly suppressed HIF-1 mRNA expression in renal tissue. This decrease was correlated with TNF-a and caspase-3 levels (p<0.001).

Conclusion:

Chronic Cd administration induces, inflammation, apoptosis in rat kidney. HIF-1 is proposed to be an important molecule in anti-apoptotic responses. Our results showed that Cd is one of regulator of HIF-1 and hypoxia inducible genes. Cd, induces toxicity not only by proinflammatory mechanism but also blocking endogenous protective mechanism of the body, HIF-1 mRNA expression.