This pilot proposal examines the potential of using a model insect species for assessing oxidative stress exerted by an anticancer drug mitomycin C, and an antifungal compound, dichlone. The focus of this research is towards the development of a nonmammalian model for biomedical research. Fundamental processes of free-radical mediated oxygen toxicity exacerbated by exogenous prooxidant drugs and environmental toxins are similar in almost all aerobic organisms. Our recent research supports the contention that in insects and mammals these prooxidants induce oxidative stress by generation of activated forms of oxygen, inducing life-threatening lipid peroxidation and other deleterious effects on cellular processes. Oxidative stress is a chain-event, and a single initiating event caused by a prooxidant may cascade into a widespread chain reaction that produces many deleterious products in concentrations many magnitudes greater than the initiator. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase activity of glutathione transferase (GSTPX) and glutathione reductase (GR) are considered crucial for termination of the oxygen radical cascade and lipid peroxidation chain reaction. DT-diaphorase is also an important antioxidant for reducing quinones without the intermediacy of the semiquinone radicals which are notorious generators superoxide anion radicals. The activities of these enzymes are altered in response to increased oxidative stress such as by ingestion of a prooxidant. Thus, the proposed research is specifically aimed at assessing oxidative stress from chronic exposures of mitomycin C and dichlone to larvae of a polyphagous insect species, the southern armyworm (Spodoptera eridania), which possesses these antioxidant enzymes. However, this pilot study represents first attempt to demonstrate oxidative stress from prooxidants of biomedical interest. This study will generate results relevant to the oxidative stress based on several criteria (i.e. lipid peroxidation, antioxidant enzyme levels, and the ratio of reduced vs. oxidized glutathione). In turn, this will enable us to determine whether results obtained using a nonmammalian model species are applicable to studies of the oxidative stress in mammalian systems.
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NIH ExPorter