Selenium Effects on the Cytotoxicity and Lung Fibrosis Induced by Silica

Abstract

The initial event after inhalation of quartz particles is their damaging effect on macrophages, which represent hte most critical cells involved in the pathogenesis of silicotic fibrosis (1,ll). Our previous studies (4,5,6,7,8,9), documented also by other authors (2,3,10,14) provided support for the assumption that lipid peroxidation may be one of the quartz cytotoxic mechanisms in cells and lung tissue. There is evidence that a cooperative antioxidative defense system located within the biological structures can protect against cellular peroxidative damage (12,13). As selenium is intimately linked with the antioxidative system, the present paper was conducted to investigate the in vitro and in vivo effects of this trace element on the quartz induced cytotoxic damage in macrophages and pulmonary fibrosis.Guinea pig peritoneal macrophages were incubated with quartz standard dust (Ddrentruper) of 3 1-1 size and selenium (Na SeO 5H 0). The criteria for the assessment of cell membrane intggris; mgasurements were made on cell ciability (erythrosin exclusion), adherence, migration, lactate dehydrogenase (LDH) and acid phosphatase (AP). The peroxidative damage was estimated by lipid peroxide release (TBA-reaction), glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) activities.Experiments in vivo were performed on rats divided into 4 groups: 1.control, intratracheally instilled with lml saline; 2 . selenite-supplemented (1 ppm) in drinking water for 90 days; 3. quartz intratracheally instilled with a single dose of 30 mg dust; .slenite-supplemented and quartz-trated rats. The animals were killed at 60 days after dust administration. Wet lung and lymph node weights, lipid, phospholipid and hydroxiproline content of the lungs were determined in order to estimate the in vivo fibrosis proliferation. Fig. 1, 2 and 3, reporting the in vitro results, give evidence of selenium protection against quartz cytotoxic action on cell viability, adhesiveness, migration, LDH and AP release. When selenium was added to cell cultures the antioxidant enzyme activities, GHS-ps and SOD, as well as lipid peroxide levels restored to the control cell values.