<p>Dependence of the severity of the systemic inflammatory response on resistance to hypoxia in male Wistar rats</p>

Abstract

The aim of the study was to characterize the severity of the systemic inflammatory response induced by lipopolysaccharide (LPS) in animals with different resistance levels to hypoxia. Materials and methods: Two to three months old male Wistar rats (220-240 g) were divided according to hypoxia tolerance in a hypobaric chamber. After a month, they were injected intraperitoneally with Escherichia coli LPS at a dose of 1.5 mg/kg. After 3, 6 and 24 hours of LPS injection, we studied the levels of IL-1β, C-reactive protein (CRP) and TGF-β in the serum, the expression of Hif-1α and Nf-kb in the liver, morphological disorders in the lung and ex vivo production of IL-10 by splenic cells activated by ConA. Results: In the early periods after the injection of LPS, increase in Nf-kb expression in the liver was observed only in the rats susceptible to hypoxia. After 6 hours of LPS injection, the number of neutrophils in the interalveolar septa of the lungs of rats susceptible to hypoxia was higher than in tolerant rats. This points to the development of more pronounced LPS-induced inflammation in the rats susceptible to hypoxia and is accompanied by increased expression of Hif-1α in the liver after 6 hours of LPS administration, serum IL-1β level after 3 hours and CRP level after 24 hours. The production of the anti-inflammatory cytokine IL-10 by the spleen was significantly decreased after 6 hours of LPS injection only in the animals tolerant to hypoxia. After 24 hours of LPS injection, a significant decrease in serum TGF-β level occurred in the rats tolerant to hypoxia in comparison with the control group, which improved the survival rates of the animals. Conclusion: We have demonstrated the differences in the severity of the LPS-induced inflammatory response in male Wistar rats with different resistance levels to hypoxia. Rats susceptible to hypoxia are characterized by a more pronounced inflammatory response induced by LPS.

Differences in Tolerance to Hypoxia: Physiological, Biochemical, and Molecular-Biological Characteristics

“…Clinical and pathophysiological studies, focused on the research on the effect of high-altitude conditions on the organism, made it possible to distinguish two polar groups of laboratory animals and humans according to their ability to adapt to the lack of oxygen and differences in their basic resistance to hypoxia [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. In experimental studies, according to the results of the survival time (the time before respiratory disturbances and signs of asphyxia appear) in an assessment under conditions of hypobaric hypoxia, animals are divided into tolerant and susceptible to oxygen deficiency.…”

“…One of the most common methods for determining tolerance to oxygen deficiency is a model that reproduces the conditions of hypobaric hypoxia in decompression chambers, into which volunteers, pilots, astronauts or experimental animals are set [ 9 , 10 , 11 , 12 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 123 , 124 , 125 , 126 , 127 , 128 , 129 ]. To assess the individual’s hypoxia tolerance, people are exposed to altitudes of several thousand meters [ 99 , 101 , 130 ].…”

“…Experimental models of high-altitude human diseases mostly include the use of a decompression chamber [ 189 , 190 , 191 ]. Additionally, among experimental animals, the most common method for determining tolerance to oxygen deficiency is a model that reproduces the conditions of hypobaric hypoxia in decompression chambers by the controlled pumping out of air [ 11 , 14 , 18 , 19 , 128 ].…”

“…Usually for experimental animals, extreme altitudes, corresponding to respiratory disturbances and signs of asphyxia, are used. For outbred rats and Wistar rats, 11000–11500 m altitudes are used; for Sprague–Dawley rats, 9250–10668 m [ 9 , 11 , 12 , 14 , 18 , 19 , 126 , 192 , 193 , 194 ]. Another method for determining individual tolerance to hypoxia was proposed: a stepwise “ascent” of animals in a decompression chamber to platforms, corresponding to different altitudes until the recording of agonal breathing [ 195 ].…”

“…Oxygen deficiency is one of the key factors in the development of infectious, inflammatory, and tumor diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. It is known that basic tolerance to hypoxia in humans and various animal species differs [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. The differences in basic tolerance to oxygen deficiency can determine the predisposition to the development of hypoxia-related disorders.…”