Carbon Tetrachloride (Infliximab)

INTRODUCTION
Carbon tetrachloride (CCl4) - an organic industrial solvent used in industry – is a vigorous carcinogenic agent that may create dysfunction of lung, liver, kidney and nervous system (1, 2). After being absorbed from gastrointestinal system, respiratory system and skin CCl4 is metabolized by cytochrome P-450 and exerts its toxic effects via its metabolites trichloromethyl free radical and trichloromethyl peroxyl radical (1-3). These free radicals interacts with fatty acids of lung cell membrane and increase lipid peroxidation and DNA fragmentation. Moreover, they suppress antioxidant enzymes including catalase, superoxide dismutase, glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase and glutathione peroxide (1,2,4).

In various invitro studies that used human fibroblasts, endothelial cells, neutrophils, lymphocytes, and epithelial cells CCl4 was reported to inhibit TNF-α functions (7). Also, it was shown to prevent various tissues against ischemia reperfusion injury (8,9). TNF-α leads to tissue injury by increasing cytokines production and increasing ROS formation and stimulating direct caspases pathway (10). Ib has been reported to prevent cytokines production and ROS formation induced by various drugs toxicity in tissues such as lung, kidney and liver tissues via blocking TNF-α (8, 11, mtx-inf akciğer buraya kaynak olarak ekle). In literature the chronic toxic effects of CCl4 have been investigated. In this study, we aimed to investigate whether high dosage of CCl4 causes acute damage to lung tissue and to investigate its effect on cytokines production, oxidative stress and apoptosis. Our second aim was to investigate whether Ib has a preventable effect on CCl4 induced acute pulmonary

TNF-α also leads to apoptosis by direct stimulation of caspase pathway and tissue injury. It is known that TNF-α leads to lung toxicity during inflammation and the toxicity induced by drugs or organic substances. It is known that tissue NO increases after inflammation. Due to its high production NO reacts with superoxide radicals leading to the formation of peroxynitrite radicals. The resulting peroxynitrite radicals are highly toxic to the tissue (20). CCl4 leads to tissue injury in various tissues by increasing TNF-α and NO production (21). Studies conducted on Ib have shown it to suppress cytokine release and to decrease peroxynitrite radicals by increasing NO level. Our study has shown that the intensive release of TNF-α and NO during acute CCl4 toxicity causes lung tissue injury by the formation of peroxynitrite radicals and ROS. Ib may lower ROS formation by blocking TNF-α