Long-term exposure to arsenic in drinking water leads to myocardial damage by oxidative stress and reduction in NO.

Chronic arsenic exposure causes myocardial damage. The aim of this study is to investigate if oxidative stress and reduction in NO is involved in the myocardial damage induced by arsenic in drinking water. Rats were divided into a control group and different doses of sodium arsenite. With increasing sodium arsenite concentrations in drinking water, localised inflammatory foci and necrotic myocardial tissues were gradually observed. Compared to the control group, the activities and gene expression of antioxidant enzymes in arsenic-exposed rats decreased. NO content and the NOS activity as well as the expression of NOS mRNA in the myocardial tissue of exposed rats, decreased, and the extracellular NO content of cardiomyocytes treated with sodium arsenite also decreased. The rate of cell apoptosis induced by sodium arsenite decreased after treatment with sodium nitroprusside (an NO donor). In conclusion, arsenic exposure in drinking water can lead to myocardial injury and cardiomyocyte apoptosis through oxidative stress and a reduction in NO content.

Endoplasmic reticulum stress pathway mediates T-2 toxin-induced chondrocyte apoptosis.

T-2 toxin leads to chondrocyte apoptosis and excessive extracellular matrix degradation. The aim of this study is to investigate if endoplasmic reticulum stress (ERS) - initiated apoptosis is involved in the chondrocyte damage induced by T-2 toxin. In vivo, rats were divided into a control group, T-2 toxin 200 ng/g BW/d group, the protein levels of GRP78, CHOP, and caspase-12 were detected using immunohistochemistry in articular cartilage tissues. In vitro, C28/I2 and ATDC5 chondrocytes were treated with various concentrations of T-2 toxin. For the salubrinal protection assay, cells were pretreated with 20 µM salubrinal for 1 h, and treated with and without T-2 toxin for 24 h. The cell viability was determined using the MTT assay; and the cell apoptosis was determined using the Flow Cytometry Assay; the mRNA and protein levels of the ERS markers and ECM were determined using RT-PCR and western blotting. This study found that the expressions of GRP78, CHOP, and caspase-12 is higher in T-2 toxin group than in control group both in vivo and in vitro, and the T-2 toxin administration promoted chondrocyte apoptosis, suppressed matrix synthesis, and accelerated cellular catabolism via the ERS signaling pathway. In addition, this study found that salubrinal prevented chondrocyte injury by inhibiting ERS-mediated apoptosis via the PERK-eIF2α-ATF4-CHOP signaling pathway. Collectively, this study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage, and presents a novel therapeutic possibility of salubrinal for Osteoarthropathy such as osteoarthritis (OA) and Kaschin-Beck disease (KBD).

The dorsal and the ventral side of hypoglossal motor nucleus showed different response to chronic intermittent hypoxia in rats.

PURPOSE: To study neurochemical reactions to chronic intermittent hypoxia (CIH) in the hypoglossal nucleus (HN) of rats. METHODS: Adult male Sprague-Dawley rats (n = 12) were randomly divided into two groups (the CIH and the control group). The CIH rats were housed in a hypoxic chamber with the fraction of oxygen volume alternating between 21% and 5% by providing air for 60 s and then providing nitrogen for 60 s from 8:30 am to 16:30 pm each day for 35 days. The control group was housed in a cabin with normal oxygen levels. We studied the expression of c-fos protein, 5-hydroxytryptamine (5-HT) positive terminals, and its 2A receptors in hypoglossal nuclei by immunohistochemistry. RESULTS: The expression of c-fos, 5-HT positive terminals, and accordingly 5-HT 2A receptors in the CIH group were significantly higher than that in the controls (p < 0.05). The ventral side of the HN showed a clearly higher expression of 5-HT and its 2A receptors than the dorsal side (p < 0.05). CONCLUSION: There were 2 responses of the HN to CIH. First, CIH induced a higher expression of 5-HT positive terminals and its 2A receptors, and second, this reaction was much more evident in ventral side than in the dorsal side. We postulate that these responses may serve to be a protective and compensatory mechanism for CIH.