Aerobic organisms by definition require oxygen, and the importance of iron in aerobic respiration has long been recognized, but despite their beneficial roles, these elements can pose a real threat to the organism. During oxygen reduction, reactive species such as O2-. and H2O2 are formed readily. Iron can combine with these species, or with molecular oxygen itself, to generate free radicals which will attack the polyunsaturated fatty acids of membrane lipids. This oxidative deterioration of membrane lipids is known as lipid peroxidation. To protect itself against this form of attack, the organism possesses several types of defense mechanisms. Under normal conditions, these defenses appear to offer adequate protection for cell membranes, but the possibility exists that certain foreign compounds may interfere with or even overwhelm these defenses, and herein could lie a general mechanism of toxicity. This possible cause of toxicity is discussed in relation to other suggested causes.

Lipid peroxidation and mechanisms of toxicity.

Liposomes as membrane model for study of lipid peroxidation.

The effect of ionizing radiation on lipid membranes

Jagetia, G. C., Baliga, M. S., Venkatesh, P. and Ulloor, J. N. Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation. Radiat. Res. 160, 584–592 (2003). The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6–12 Gy of γ radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 150 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in t...

Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation

Modulation of radiation-induced alteration in the antioxidant status of mice by naringin.

Cellular membranes have been suggested as possible loci for the development of the oxygen effect in radiobiology. Unsaturated lipids from membranes are subject to very efficient radiation-induced peroxidation, and the deleterious effects generally associated with lipid autoxidation could be initiated by ionizing radiation. Oxidative damage in lipids is characterized not only by high yields but also by a profound dose-rate effect. At dose-rates of X-irradiation below 100 rad/min, a very sharp rise occurs in oxidative damage. This damage has been quantified spectrophotometrically in terms of diene conjugation (O.D. 234 mm) and chromatographically in terms of specific 9- and 13-hydroperoxide formation in linoleic acid micelles. Radical scavenging experiments indicate that hydroxyl radical attack initiates the oxidative damage. Dimethyl sulphoxide is exceptional in that it does not protect, but sensitizes, linoleic acid to radiation induced peroxidation. The yields of hydroperoxides are substantial (G=10--40) and can be related to biological changes known to be effected by autoxidizing lipids.

B Gaboury

Papers

Dose-rate and oxygen effects in models of lipid membranes: linoleic acid.