Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

Hepatocytes display a compensatory survival response against cadmium toxicity by a mechanism mediated by EGFR and Src.

Although the liver is a cadmium-target organ, hepatocyte response involved in its toxicity is not yet elucidated. A link between this heavy metal treatment and Stat3 signaling pathways was examined in primary mouse hepatocytes. We provided evidence of a novel link among NADPH oxidase and Stat3 signaling, mediated by Src, EGFR, and Erk1/2. Cadmium activates NADPH oxidase. ROS produced by this oxidase activates Src, enable that in turn, transactivates EGFR that activates Stat3 in tyrosine, allowing its dimerization. Also, ROS from NADPH oxidase favors ERK1/2 activation that phosphorylates Stat3 in serine, resulting in a compensatory or adaptive survival response such as production of metallothionein-II in short Cd exposure times. However, after 12h CdCl2 treatment, cell viability diminished in 50%, accompanied by a drastic decrease of metallothionein-II production, and an increase in p53 activation and the pro-apoptotic protein Bax.

Analysis of the DNA damage induced by praziquantel in V-79 Chinese hamster fibroblasts and human blood cells using the single-cell gel electrophoresis assay.

The analysis of the genotoxicity of praziquantel, an effective antihelminthic widely used in countries where parasitic infections are still serious public health problems, has been extensively performed using diverse in vitro and in vivo assays and endpoints. However, results are not conclusive, since reports to date indicate either praziquantel is mutagenic, comutagenic, or even antimutagenic. In the present work, the clastogenic potential of praziquantel was investigated in V-79 Chinese hamster fibroblasts and human peripheral blood using a sensitive technique such as the single-cell electrophoresis assay. Results indicate that even though praziquantel induced DNA single-strand breaks both in V-79 cells and unstimulated human leukocytes, this effect was not translated into persistent DNA damage, since neither SCE nor HPRT mutations were induced. This suggests that the effect observed in the SCGE assay is an early event not closely related to praziquantel mutagenicity, because this DNA damage could be efficiently repaired.