Conversely, fibrosis may contribute to oxidative stress, or both of them may be triggered by an independent mechanism. Indirect proof of abnormal oxidative stress was provided by Dooley selleck products et al, who showed that the antioxidant epigallocatechin 3 gallate can reduce extracel lular matrix production and inhibit contraction of dermal fibroblasts from systemic sclerosis patients. Furthermore, epigallocatechin 3 gallate was able to suppress intracellu lar reactive oxygen species, extracellular signal regulated kinases signaling, and nuclear factor kappa light chain enhancer of activated B cells activity. ERK, one of the relevant targets of ROS, and its upstream mediators, such as Ras family proteins, func tion as key molecules in the pathway that leads to fibrosis, and in maintaining the generation and amplification of ROS.

Levels of ROS and type I collagen were significantly higher, and amounts of free thiol were significantly lower in SSc fibroblasts compared with normal fibroblasts. Hormonal influences on the etiopathogenesis of the dis ease have been intensively studied, focusing on distur bances of the gonadal axis. A second, and as yet poorly accounted for, endocrine feature Inhibitors,Modulators,Libraries of scleroderma is its overlap with thyroid abnormalities. Of 719 patients affected by SSc, 273 had at least one other autoim mune disease, with the most frequent being autoimmune thyroid disease. Whereas the association of Graves disease with SSc is supported by case reports, the literature related to Hashimoto thyroiditis and hypothyroidism in general, either subclinical or sympto matic, in SSc patients is more robust.

It was recently demonstrated by Cianfarani et al. that thyroid stimu lating Inhibitors,Modulators,Libraries hormone receptor messenger RNA is consis tently detected in both skin biopsies and cultured primary keratinocytes and, more interestingly, Inhibitors,Modulators,Libraries in dermal fibroblasts of patients with SSc. A previous report confirmed the occurrence of a state of oxidizing stress in relation to hyperthyroidism. The aim of the study was, therefore, to evaluate the effect of propylthiouracil, administered at a dose able to induce hypothyroidism, on the extent of fibrosis in a murine model of SSc, based on reactive Inhibitors,Modulators,Libraries oxygen spe cies mediated injury. Materials and methods Animals Pathogen free, Inhibitors,Modulators,Libraries 6 weeks old female BALB c mice were purchased from Harlan, maintained with food and water ad libitum, and given human care according to institutional guidelines.

The project was reviewed and approved by the Ethics Committee of the University of Messina. All mice were housed in single cages under controlled light and temperature conditions. Mice were randomized in three arms, HOCl alone, HOCl plus propylthiouracil, or vehicle alone for 6 weeks. ROS preparation and treatments SSc was induced as characterized in prompt delivery detail in the Cochin chronic oxidant stress model. In brief, hypochlorous acid was produced by adding 166 ul of sodium hypochlorite solution to 11.