Effects of bacterial endotoxin on protecting copper-deficient rats from hyperoxia

Abstract

The administration of very low doses of bacterial endotoxin protects rats during exposure to hyperoxia and is associated with the induction of lung antioxidant enzyme activities. Copper-deficient rats have increased susceptibility to O2 toxicity, which may be related to their decreased lung superoxide dismutase activity (SOD) or decreased plasma ceruloplasmin concentrations. To determine whether endotoxin can protect against hyperoxia in this susceptible model, we exposed copper-deficient and control rats to a fractional inspiratory concentration of O2 greater than 0.95 for 96 h after pretreatment with 500 micrograms/kg of bacterial endotoxin or phosphate-buffered saline (PBS). Mortality in the copper-deficient and control rats given PBS and exposed to O2 for 96 h was 100%. Copper-deficient rats died significantly earlier during the exposure than controls. No mortality occurred in either group treated with endotoxin and hyperoxia despite the decreased activity of copper-dependent enzymes in the copper-deficient rats. Copper-deficient rats treated with endotoxin and exposed to hyperoxia did increase lung Cu-Zn-SOD activity, but activity remained below levels found in air-exposed controls. Mn-SOD activity was found to be induced above air-exposed controls in the copper-deficient rats treated with endotoxin and exposed to hyperoxia. Hyperoxic exposure resulted in a marked increase in plasma ceruloplasmin concentrations in the control rats, but no increases in ceruloplasmin occurred in the copper-deficient animals. Endotoxin protects copper-deficient rats from hyperoxia despite their decreased lung Cu-Zn-SOD activity, and decreased plasma ceruloplasmin.

Essential Trace Elements in Antioxidant Processes

“…Similar to the ethanol-exposed fetus, this phenomenon is probably a protective response to the generation of free radicals resulting from ethanol metabolism. Similar to ADR and alcohol, other potential free radical generators whose toxicity has been reported to be increased under conditions of Cu deficiency include carbon tetrachloride and hyperoxia (37,42). Thus, whereas this is still an evolving area of research, current evidence supports the idea that the toxicity of compounds that produce free radicals via their metabolism are enhanced under conditions of Cu deficiency owing to an impairment in the antioxidant system.…”

Dietary manipulation of the inflammatory response

“…https://doi.org/10.1079/PNS19920039 The question of whether deficiencies in trace elements interfere with the production of these proteins during inflammation has been addressed in any detail only for Cu and Zn. The ability of rats to increase plasma caeruloplasmin and Cu-Zn superoxide dismutase in lung, in response to the dual stress of endotoxin and high oxygen concentrations, is impaired by Cu deficiency (Spence et al 1986). Likewise the ability of IL-1 to increase plasma concentrations of fully functional CP is also suppressed (Barber & Cousins, 1988).…”

Analytic Reviews : Oxygen Toxicity

“…This means that in the selenium-deficient animal mechanisms other than antioxidant enzyme induction provide early protection from hyperoxia. Copper-deficient rats could not increase lung concentrations of copper and zinc SOD, but lung manganese SOD concentrations were found to be induced by endotoxin [27]. Block [81] found that rats pretreated with endotoxin had significantly reduced mortality during exposure to hyperoxia and were also protected against hyperoxia-induced injury to the pulmonary capillary endothelium, which is manifested by depression of amine uptake (p < 0.05).…”

“…Copper-deficient animals have decreased lung activity of the copper and zinc form of SOD and also exhibit increased susceptibility to oxygen lung damage [26,27]. Vitamin E deficiency in rats has been shown to increase the toxic effects of oxygen [28].…”

“…Enzyme induction may be one of the important mechanisms responsible for protective effects. Jenkinson and Spence and their associates [25,27], however, found that endotoxin also protects both seleniumdeficient rats and copper-deficient rats from hyperoxia. Selenium-deficient rats normally would die from hyperoxia earlier than the time period required for enzyme induction.…”