Erythrocytes of Little Ground Squirrels Undergo Reversible Oxidative Stress During Arousal From Hibernation.

Elena R Nikitina,Nisred K Klichkhanov,Zainab M Shihamirova,Shamil I Chalabov,Maria D Astaeva,Aleksandr I Krivchenko

doi:10.3389/fphys.2021.730657

Elena R Nikitina, Nisred K Klichkhanov + Show 4 more

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https://doi.org/10.3389/fphys.2021.730657

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Abstract

The hibernation of small mammals is characterized by long torpor bouts alternating with short periods of arousal. During arousal, due to a significant increase in oxygen consumption, tissue perfusion, and the launch of thermogenesis in cells, a large amount of reactive oxygen species (ROS) and nitrogen (RNS) can be formed, which can trigger oxidative stress in cells. To estimate this possibility, we studied the intensity of free-radical processes in the red blood cells (RBCs) of little ground squirrels (LGS; Spermophilus pygmaeus) in the dynamics of arousal from hibernation. We found that in the torpid state, the degree of generation of ROS and RNS (8.3%, p>0.09; 20.7%, p<0.001, respectively), the degree of oxidative modification of membrane lipids and RBC proteins is at a low level (47%, p<0.001; 82.7%, p<0.001, respectively) compared to the summer control. At the same time, the activity of superoxide dismutase (SOD) and catalase (CAT) in RBC is significantly reduced (32.8%, p<0.001; 22.2%, p<0.001, respectively), but not the level of glutathione (GSH). In the torpid state, SOD is activated by exogenous GSH in concentration-dependent manner, which indicates reversible enzyme inhibition. During the arousal of ground squirrels, when the body temperature reaches 25°C, RBCs are exposed oxidative stress. This is confirmed by the maximum increase in the level of uric acid (25.4%, p<0.001) in plasma, a marker of oxidative modification of lipids [thiobarbituric acid reactive substances (TBARS); 82%, p < 0.001] and proteins (carbonyl groups; 499%, p < 0.001) in RBC membranes, as well as the decrease in the level of GSH (19.7%, p < 0.001) in erythrocytes relative to the torpid state and activity of SOD and CAT in erythrocytes to values at the Tb 20°C. After full recovery of body temperature, the level of GSH increases, the ratio of SOD/CAT is restored, which significantly reduces the degree of oxidative damage of lipids and proteins of RBC membranes. Thus, the oxidative stress detected at Tb 25°C was transient and physiologically regulated.

Highlights

Homeothermic animals in winter face a vitally important problem of maintaining temperature homeostasis, which is indispensable for survival
At the beginning of arousal, when Tb increased from 4 to 10°C due to passive warming, the WR was 0.25°C/min, with subsequent self-warming occurring at WR of 0.14°C/min; within the Tb range of 17–35°C, the WR increased to 0.51°C/min
A significant increase in the plasma Nitric oxide (NO) level that we found after the Tb rose up to 25°C appears to be important for the acceleration of blood flow, which is necessary to rewarm the posterior part of the body

Summary

Introduction

Homeothermic animals in winter face a vitally important problem of maintaining temperature homeostasis, which is indispensable for survival. Some homeothermic animals developed several adaptive strategies that allowed them to endure extreme conditions. One of these strategies is hibernation, which is employed by some mammals to evade such challenges as shorter daylight hours, low ambient temperatures, and scarce food supply in winter time (Ruf and Geiser, 2015; Staples, 2016). In the Arctic ground squirrels (Spermophilus parryii), oxygen uptake during hibernation drops by more than 90% lowering thereby body temperature (Tb) almost to the ambient level (1–5°C; Tøien et al, 2001; Geiser, 2004). Blood pressure can drop from 130/80 to 90/30 mmHg, and cardiac output – to 1/60 of the euthermic level (Geiser, 2004)

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