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Depression of glutathione by cold-restraint in mice
H F Simmons1, R C James, R D Harbison
1Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock.
Abstract:
The effects of cold-restraint as a physiological stressor on the glutathione (GSH) content of the liver and other tissues were examined in male mice. Mice of the ICR, NIH, ND/4, and B6C3F1 strains subjected to cold-restraint for 2 or 3 h experienced a loss of hepatic GSH concentrations ranging from approximately 15 to 50%. Though 3 of these strains (ICR, NIH, and B6C3F1) experienced hypothermia as result of the cold-restraint treatment, with average decreases in core body temperature ranging from 3.3 to 9.8 degrees C, hepatic GSH levels were depressed in the ND/4 mouse in the absence of changes in core body temperature. The ability of cold-restraint as a stressor to diminish hepatic GSH therefore could not be attributed simply to hypothermia. The decrease in hepatic GSH from cold-restraint in ND/4 mice was paralleled by a decrease in non-protein sulfhydryl (NPSH) content of the liver. In addition to its effects on liver GSH and NPSH concentrations, 1.5 h of cold-restraint stress significantly depressed plasma, heart, kidney, and lung NPSH concentrations. The extent of NPSH depression was equivalent to the GSH depression in the liver, heart, and kidney, despite the observation that the normal contribution of GSH to total NPSH content in these tissues ranged from a high of 89% (liver) to a low of 49% (heart). These results with cold-restraint in the ND/4 mouse suggest that other stressors may significantly depress cellular concentrations of GSH and other thiols, and may thereby render the affected tissues more susceptible to the toxicity of free radicals, electrophilic xenobiotic metabolites, or reactive oxygen species.
Insights
Cold-restraint stress significantly depletes liver glutathione (GSH) and non-protein sulfhydryl (NPSH) levels in mice, independent of hypothermia. This depletion may increase susceptibility to oxidative stress and toxicity.
Area of Science:
- Biochemistry
- Physiology
- Toxicology
Background:
- Glutathione (GSH) is a critical endogenous antioxidant.
- Physiological stressors can impact cellular redox balance.
- Understanding stressor effects on GSH is vital for predicting tissue vulnerability.
Purpose of the Study:
- To investigate the impact of cold-restraint stress on hepatic and tissue glutathione (GSH) and non-protein sulfhydryl (NPSH) levels in mice.
- To determine if hypothermia is the primary driver of GSH depletion under stress.
Main Methods:
- Male mice of four strains (ICR, NIH, ND/4, B6C3F1) were subjected to cold-restraint stress for 2-3 hours.
- Core body temperature and tissue GSH/NPSH concentrations were measured.
- Data were analyzed to correlate stress, hypothermia, and thiol levels.
Main Results:
- Cold-restraint stress reduced hepatic GSH by 15-50% across strains.
- GSH depletion occurred in ND/4 mice without significant hypothermia.
- Cold-restraint also decreased NPSH in liver, plasma, heart, kidney, and lung.
Conclusions:
- Cold-restraint stress depletes hepatic GSH and NPSH, independent of hypothermia.
- Reduced thiol levels may enhance susceptibility to reactive oxygen species and xenobiotic toxicity.
- This highlights the broader impact of stressors on cellular defense mechanisms.