Thiram inhibits angiogenesis and slows the development of experimental tumours in mice

Abstract

Thiram-tetramethylthiuram disulphide -a chelator of heavy metals, inhibited DNA synthesis and induced apoptosis in cultured bovine capillary endothelial cells. Bovine capillary endothelial cells were 10 -60-fold more sensitive to thiram than other cell types. These effects were prevented by addition of antioxidants, indicating involvement of reactive oxygen species. Exogenously added Cu 2+ impeded specifically and almost completely the inhibitory effect of thiram for bovine capillary endothelial cells. Moreover, thiram had markedly inhibited human recombinant Cu/Zn superoxide dismutase enzymatic activity (85%) in vitro. Moreover, PC12-SOD cells with elevated Cu/Zn superoxide dismutase were less sensitive to thiram treatment than control cells. These data indicate that the effects of thiram are mediated by inhibition of Cu/Zn superoxide dismutase activity. Oral administration of thiram (13 -30 mg mouse 71 ), inhibited angiogenesis in CD1 nude mice. Tumour development is known to largely depend on angiogenesis. We found that oral administration of thiram (30 mg) to mice caused significant inhibition of C6 glioma tumour development (60%) and marked reduction (by 3 -5-fold) in metastatic growth of Lewis lung carcinoma. The data establish thiram as a potential inhibitor of angiogenesis and raise the possibility for its use as therapy in pathologies in which neovascularisation is involved, including neoplasia.

Tetramethylpyrazine Mitigates Toxicity and Liver Oxidative Stress in Tibial Dyschondroplasia Chickens

“…Development of poultry tibial cartilage is coordinated with each other in a variety of enzyme, and most of the enzymes transform, mature and metabolize in the liver. It has been testified that thiram markedly prevent the GSH and SOD activity in human which leads to oxidative stress and imbalance (Marikovsky, 2002). This type of oxidative stress effects the lipid peroxidation of cell membrane and ultimately release of MDA as an end product (Perry et al, 2010;Shahzad et al, 2014a).…”

Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response

“…Disulfiram (DSF), a chelator of heavy metals and the active ingredient of the drug Antabuse used in aversion therapy for chronic alcoholism (4), inhibits SOD-1 in vivo (5). Recently, we demonstrated that transgenic mice overexpressing SOD-1 (Tg-SOD) have a higher angiogenic potential and that DSF inhibits SOD-1, induces oxidative stress and apoptosis in endothelial cells in vitro, and inhibits angiogenesis and tumor growth in vivo (6,7).…”

Salvia Miltiorrhiza Reinstates Growth Plate Width, Reduces Liver Oxidative Stress and Toxicity in Avian Tibial Dyschondroplasia

“…Some authors described that thiram is an oxidant agent, ultimately increased oxidative stress on liver and lead to decreased in antioxidant (SOD and GSH-Px) activities (Li et al, 2007;Marikovsky, 2002). MDA is well-known cell membrane injury marker, lipid peroxidation resulting in release of MDA product in the end (Marikovsky, 2002;Nabi et al, 2016b;Shahzad et al, 2014).…”

“…MDA is well-known cell membrane injury marker, lipid peroxidation resulting in release of MDA product in the end (Marikovsky, 2002;Nabi et al, 2016b;Shahzad et al, 2014). Thiraminduction can lead to TD disease causes liver damages with increasing of liver damages indicators (AST and ALT) in blood and toxicity (Gupta and Amma, 1993;Li et al, 2007;Shahzad et al, 2014;Nabi et al, 2016a).…”

“…Liver toxicity and oxidative stress is considered to mutual pathological mechanism due to several inflammatory or pathological conditions in animals Marikovsky, 2002). Diverse factors induce toxicity and oxidative stress and the liver is the principal detoxifying organ that directly impairs the production performance of chicken.…”