High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons

Life Sciences ◽  
2021 ◽  
pp. 119614
Author(s):  
Yanhong Xu ◽  
Shiqiao Peng ◽  
Xinyu Cao ◽  
Shengnan Qian ◽  
Shuang Shen ◽  
...  
2020 ◽  
Author(s):  
Yanhong Xu ◽  
Shiqiao Peng ◽  
Xinyu Cao ◽  
Shengnan Qian ◽  
Shuang Shen ◽  
...  

AbstractBackground and purposeSodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. However, the toxic effect of SB remains largely unknown. This issue is addressed in current study.Experimental approachSB (0.3 – 2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brain hypothalamus were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect.Key resultsThe temperature was reduced by SB (1.2 −2.5 g/kg) in a dose-dependent manner in mice for 2-4 hr. In the brain, the effect was associated with SB elevation and neurotransmitter (Glutamate and GABA) reduction. The mitochondria exhibited a transient volume expansion and crista loss in the hypothalamic neurons. ADP/ATP ratio was increased with accumulation of intermediate metabolites in the glycolysis, TCA cycle and pentose phosphate pathways. The mitochondrial protein, adenine nucleotide transporter (ANT), was activated for proton transportation leading to a transient potential collapse by proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. The temperature drop was attenuated by i.p. injection of norepinephrine. The HDAC inhibitors, such as SAHA and pyruvate, did not exhibit the same effect.Conclusion and implicationsSuper-dosed SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial reprogramming in the brain. The mechanism was quick activation of ANT proteins for the proton leak in mitochondria.


1989 ◽  
Vol 72 (2) ◽  
pp. 384-386 ◽  
Author(s):  
A W McCulloch ◽  
R K Boyd ◽  
A S W de Freitas ◽  
R A Foxall ◽  
W D Jamieson ◽  
...  

Abstract Toxicity (extreme weakness, body temperature drop, cyanosis, some slow deaths) in test mice, upon intraperitoneal injection of standardmethod paralytic shellfish poison (PSP) extracts of some PSP-free oysters, is consistent with the relatively high levels of zinc in these extracts. As a rough guideline, the threshold for a toxic response corresponds to a drained tissue zinc level of over 900 μg/g. The identification of zinc as the substance responsible has been supported by inducing toxicity in control extracts by spiking with nontoxic levels of zinc, and by eliminating toxicity from toxic extracts by chemical removal (precipitation, ion exchange) of metals.


1955 ◽  
Vol 33 (1) ◽  
pp. 654-657
Author(s):  
Roscoe G. Bartlett Jr. ◽  
Vernon C. Bohr ◽  
William I. Inman

Forty adult Sprague-Dawley rats were divided into four groups: 10 control and 10 restrained animals at room temperature [Formula: see text] and 10 control and 10 restrained animals at [Formula: see text]. Continuous recordings were made on oxygen consumption and body temperature. It was learned that the restrained animals had an initially higher oxygen consumption than the control animals. This gradient was maintained throughout a three-hour exposure in the case of the animals maintained at room temperature but in the case of the animals maintained in the cold it was reversed early in the tests, i.e., the oxygen consumption of the restrained animals fell below that of the control animals. The fall in oxygen consumption was accompanied by a fall in body temperature. From the data it was not possible to state which was the cause and which was the effect. It was suggested that both decreased oxygen consumption and temperature drop may be the effect of another cause, emotionality or emotional stress.


1955 ◽  
Vol 33 (4) ◽  
pp. 654-657 ◽  
Author(s):  
Roscoe G. Bartlett Jr. ◽  
Vernon C. Bohr ◽  
William I. Inman

Forty adult Sprague-Dawley rats were divided into four groups: 10 control and 10 restrained animals at room temperature [Formula: see text] and 10 control and 10 restrained animals at [Formula: see text]. Continuous recordings were made on oxygen consumption and body temperature. It was learned that the restrained animals had an initially higher oxygen consumption than the control animals. This gradient was maintained throughout a three-hour exposure in the case of the animals maintained at room temperature but in the case of the animals maintained in the cold it was reversed early in the tests, i.e., the oxygen consumption of the restrained animals fell below that of the control animals. The fall in oxygen consumption was accompanied by a fall in body temperature. From the data it was not possible to state which was the cause and which was the effect. It was suggested that both decreased oxygen consumption and temperature drop may be the effect of another cause, emotionality or emotional stress.


2007 ◽  
Vol 292 (1) ◽  
pp. R176-R185 ◽  
Author(s):  
Caroline Gilbert ◽  
Yvon Le Maho ◽  
Martine Perret ◽  
André Ancel

Huddling is the key energy-saving mechanism for emperor penguins to endure their 4-mo incubation fast during the Antarctic winter, but the underlying physiological mechanisms of this energy saving have remained elusive. The question is whether their deep body (core) temperature may drop in association with energy sparing, taking into account that successful egg incubation requires a temperature of about 36°C and that ambient temperatures of up to 37.5°C may be reached within tight huddles. Using data loggers implanted into five unrestrained breeding males, we present here the first data on body temperature changes throughout the breeding cycle of emperor penguins, with particular emphasis on huddling bouts. During the pairing period, core temperature decreased progressively from 37.5 ± 0.4°C to 36.5 ± 0.3°C, associated with a significant temperature drop of 0.5 ± 0.3°C during huddling. In case of egg loss, body temperature continued to decrease to 35.5 ± 0.4°C, with a further 0.9°C decrease during huddling. By contrast, a constant core temperature of 36.9 ± 0.2°C was maintained during successful incubation, even during huddling, suggesting a trade-off between the demands for successful egg incubation and energy saving. However, such a limited drop in body temperature cannot explain the observed energy savings of breeding emperor penguins. Furthermore, we never observed any signs of hyperthermia in huddling birds that were exposed to ambient temperatures as high as above 35°C. We suggest that the energy savings of huddling birds is due to a metabolic depression, the extent of which depends on a reduction of body surface areas exposed to cold.


1998 ◽  
Vol 32 (3) ◽  
pp. 260-269 ◽  
Author(s):  
W. J. Kort ◽  
J. M. Hekking-Weijma ◽  
M. T. Tenkate ◽  
V. Sorm ◽  
R. VanStrik

In a series of experiments, Klebsiella pneumoniae was inoculated intratracheally into rats and mice, and the temperature of the animals was recorded twice daily using microchip transponders. Transponders are interrogated by radio frequencies and were implanted either subcutaneously or intraperitoneally. The microchip temperatures were compared with rectal temperatures taken at the same time. The purpose of the experiments was (a) to investigate the practicability and reliability of the ELAMSTM for temperature recording; (b) to compare values given by subcutaneously or intraperitoneally implanted transponders with rectal temperatures; and (c) to determine a 'temperature-cut-off point' as an alternative for 'death of the animal' as an end point for the experiment. The results showed that the ELAMSTM was easy to operate and no important drawbacks in the use of the system were observed. The temperatures generated by the transponders implanted subcutaneously and intraperitoneally did not differ significantly from rectal temperatures. In two out of three experiments on rats, it was shown that when the temperatures reached values below 36°C, the median survival time of the animals was 24 h. In the one experiment on mice the same median survival time was observed at 36°C. In one experiment using rats, however, the disease was so acute that death occurred before any temperature drop was seen. The results show that when a 36°C cut-off point is used instead of the time of death in this particular animal model, the statistical analysis was not altered, but that it would spare animals further suffering for approximately 24 h. The argument that measuring body temperature is a laborious job and stressful to the animals is overcome when the ELAMSTM system is used.


2019 ◽  
Vol 4 (3) ◽  
pp. 93-97
Author(s):  
Natalia Latjandu ◽  
Diyan Oroh

This study aims to determine the most effective dose in reducing fever in white rats induced by DPT-HB vaccine. The research method is an experimental laboratory using the method without heating for the manufacture of syrup. The results of initial temperature measurements in all treatment groups of white rats which is the normal temperature of the test animals before the DPT-HB vaccine is obtained ranged between 35.10C-37.10C. after 2 hours of DPT-HB vaccine injection, the body temperature of the white rats was measured again and the results obtained were 36,930C-38,430C. an increase in body temperature after 2 hours of injecting this vaccine compared to the results of measuring body temperature before the vaccine is injected is a sign that the test animal has experienced a fever. The negative control group which was given syrup without extract orally, showed the body temperature of the test animals had decreased as the temperature after injecting the vaccine. On the administration of alvocate leaf flavonoid syrup, the dose ¼ showed a decrease of 0.40C. For the administration of dosage flavonoid syrup extract dosage 1, it showed that the body temperature of the test animals had a temperature drop of 1,330C. And administration of Alvocado leaf flavonoid syrup extract dose 2, showed that the body temperature of the test animals had a temperature drop of 0.6 . While the administration of Alvocado leaf flavonoid extract syrup dose 3, showed that the body temperature of the test animals experienced a temperature increase of -0.2 . From the results obtained, it can be concluded that the most effective dose of antipyretic syrup of alvocado leaf flavonoid extract is dose 1.


1985 ◽  
Vol 248 (4) ◽  
pp. R471-R478 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
J. J. Spitzer

Rats were injected with doses of endotoxin ranging from 1,000 [lethal dose approximately 50% (LD50)] to 0.01 microgram/100 g, and alterations in hemodynamics, glucose kinetics, and body temperature were studied over the subsequent 4 h. Doses of 10 micrograms/100 g or less were consistently nonlethal over 72 h. Decreases in arterial blood pressure and cardiac output were evident in rats receiving 1,000-10 micrograms/100 g endotoxin. Doses of endotoxin between 1,000 and 10 micrograms produced an early hyperlactacidemia evident by 1 h, whereas the lower doses (1 and 0.1 microgram) induced elevations that exhibited a delayed temporal response. The rates of glucose appearance (Ra) and disappearance (Rd) were increased early and transiently by the higher doses of endotoxin. Lower doses increased glucose Ra and Rd between 2 and 4 h after endotoxin. A febrile response was elicited by 10, 1, and 0.1 microgram/100 g endotoxin, while hypothermia was seen in animals receiving higher doses. Thus high doses of endotoxin induced metabolic and hemodynamic alterations that were temporally associated. Very low nonlethal doses of endotoxin (up to 4 orders of magnitude less than LD50) induced metabolic changes that appeared to be independent of hemodynamic disturbances but were temporally associated with the observed hyperthermia.


1988 ◽  
Vol 412 (3) ◽  
pp. 292-296 ◽  
Author(s):  
K. E. Cooper ◽  
S. Blähser ◽  
T. J. Malkinson ◽  
G. Merker ◽  
J. Roth ◽  
...  

1998 ◽  
Vol 159 (3) ◽  
pp. 469-478 ◽  
Author(s):  
CD McMahon ◽  
TH Elsasser ◽  
DR Gunter ◽  
LG Sanders ◽  
BP Steele ◽  
...  

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.


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