Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Cadmium (Cd) is one of the toxic heavy metals spread in the environment. The primary effects of Cd poisoning are acute hepatic toxicity and chronic renal and bone toxicity. Cd is daily ingested to humans through diverse foods, such as rice, vegetables, and seafood, and through smoking. Cd accumulates in the kidney and liver due to the dietary exposure over a lifetime, because the biological half-life of Cd is very long (15–30 years). It is concerning that renal dysfunction diagnosed in elderly people may be exacerbated by Cd accumulation. Damage to the proximal tubular cells is the characteristic of Cd-induced renal toxicity. However, the precise molecular mechanism involved in Cd renal toxicity is remaining elucidated. Our previous studies demonstrated that several transcription pathways regulate Cd toxicity in proximal tubular cells. Recently, it is found that retinoic acid (RA) which coordinates the gene expressions as one of the ligands of retinoic acid receptors (RARs), reduced Cd toxicity in human proximal tubular (HK-2) cells. Moreover, the pretreatment with retinol, the precursor of RA, also reduced Cd toxicity in HK-2 cells. However, knockdown of each gene coding for RARs did not affect Cd toxicity. Besides, the treatment with RA did not affect intracellular Cd concentration in the Cd-treated HK-2 cells. Cd renal toxicity is known to involve the apoptosis pathway. Complementarily, Cd induced apoptosis in the HK-2 cells; in addition, RA reduced not only Cd-induced apoptosis but also caspase-3 activation. These results indicate that RA may protect cells from Cd toxicity through the inhibition of apoptosis, without RAR pathway nor Cd accumulation.
