On the mechanism of paraquat action on microsomal oxygen reduction and its relation to lipid peroxidation

Paraquat: model for oxidant-initiated toxicity.

“…(25) reported that paraquat inhibited rat lung microsomal lipid peroxidation, even though paraquat stimulated both NADPH oxidation and hydrogen peroxide formation. Subsequent investigations have confirmed an in vitro paraquat inhibition of lipid peroxidation in microsomes isolated from rat lung and liver (71,72) and mouse liver (26).…”

“…Redox cycling of paraquat not only results in an uncoupling of microsomal electron transport (76) but also rapidly consumes NADPH and oxygen. All three of these effects would be expected to readily inhibit NADPH-dependent lipid peroxidation, which possibly accounts for the observations in many of the in vitro studies (25,26,71,72). The possibility that paraquat would stimulate microsomal lipid peroxidation if adequate precautions were taken to maintain both NADPH and oxygen concentrations in the incubate has in fact been demonstrated (77,78).…”

“…In 1968, Gage (24) reported that anaerobic incubation of liver microsomes with NADPH (25)(26)(27) and lung (25,28,29) microsomal hydrogen peroxide production, as measured by the conversion of methanol to formaldehyde. These observations again suggested the potential for a two-electron reduction of molecular oxygen catalyzed by paraquat.…”

Oxidant injury of lung parenchymal cells.

“…Rat lung explants were processed as described earlier except they were not inflated with agarose-media that interfered with the absorbance readings in the enzyme assays. Additionally, it was necessary to use a pool of explants (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) explants per time point) for a total net weight of 60-80 mg to obtain enzyme activities in a measurable range. Control explants at incubation times of 0, 24, and 42 h and test explants exposed to 95% 02 or paraquat (1 mM) for the final 18-h period of the total incubation time (42 h) were each pooled and homogenized in 1.0 ml cold phosphate buffer (pH 7.4) by a Brinkman polytron at a setting of 10 for 60 s. The lung homogenates were centrifuged at 16,000 g x 15 min, and the supernates were assayed immediately for catalase activity by measuring the decrease in absorbance of H202 at 240 nM (13) and for SOD activity by the ferricytochrome C assay (11).…”

Effects of bipyridylium compounds on calcium release from triadic vesicles isolated from rabbit skeletal muscle

“…low concentrations, induced calcium release t apparent physiological release site in th4 reticulum (Salama & Abramson, 1984 (DeGray et al, 1991) and cause lipid peroxidation (Steffen & Netter, 1979;Ruiz-Gutierrez et al, 1991) or release of iron from ferritin (Thomas & Aust, 1986 (Endo, 1977;R0ed, 1991). We showed that, in a control.…”