Biochemical Changes in Rat Liver after 18.5 Days of Spaceflight

Abraham, S.; Lin, Chu Yuan; Volkmann, Carol M.; Klein, Harold P.

doi:10.3181/00379727-172-41566

Cited by 17 publications

(9 citation statements)

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“…(2) investigated hepatic biochemical changes in rats flown aboard the Cosmos 690, 936, and 1129 biosatellite missions. At landing, hepatic glycogen content increased by ϳ30-70% above ground-based controls (1,2,36); accumulation of fat droplets in hepatocytes was also noted (29). These findings were later supported by data collected from rats flown aboard the Cosmos 2044 and 1887 as well as the Spacelab 3 missions (29,30).…”

mentioning

confidence: 61%

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Rivera

Tcharmtchi²,

Mendoza³

et al. 2003

Journal of Applied Physiology

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Hindlimb unloading (HU) is known to induce physiological alterations in various organ systems that mimic some responses observed after exposure to microgravity. In the present study, the effects of up to 4 wk of HU on the liver were assessed in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator of hepatic injury, were measured in portal and systemic blood samples. Endotoxin was elevated by approximately 50% in portal blood samples of mice and rats but was not detectable in systemic blood. This low-grade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice as indicated by inflammation and elevated serum transaminase activities. Blood levels of the cytokine TNF-alpha were increased by approximately 50% in C57BL/6 mice; no significant elevation of this cytokine was detected in rats. Messenger RNA levels of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide binding protein were significantly enhanced after 3 wk of HU in endotoxin-sensitive rodents. In contrast, no histological changes or significant increases in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal endotoxin levels of 222 +/- 83.4 pg/ml. At the 3-wk time point, expression of acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after 4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these findings indicate that HU induced mild portal endotoxemia, which contributed to the observed hepatic injury in endotoxin-sensitive rodents.

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mentioning

confidence: 61%

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Rivera

Tcharmtchi²,

Mendoza³

et al. 2003

Journal of Applied Physiology

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“…Long stays in microgravity do not represent an intensive stressogenic stimulus for endocrine organs; and hormone alterations observed after spaceflight are suggested to be due primarily to acute stressor activity resulting from the return to Earth's gravity 16 . Activities of seven out of 28 enzymes in rat liver examined indicated changes characteristic of 18.5 day spaceflight compared with centrifuged rats 17 . These suggest that certain hepatic enzyme activities, including CYP, are more sensitive markers of microgravity than hormonal changes.…”

Section: Discussionmentioning

confidence: 85%

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Baba

Nishimura

Kuwahara

et al. 2008

Pathology International

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As the incidence and length of spaceflight increases, the need to administer pharmacological agents to crew members may become greater. The final goal is to predict the therapeutic or toxic effects of drugs, especially those with a low therapeutic index, during spaceflight. The liver is central to systemic metabolism, therefore, various drugs rely on hepatic metabolism by cytochrome P450 (CYP). The function of individual CYP enzymes is diverse because they are subject to different regulatory mechanisms and substrate specificity. Because spaceflight may be a stressor and influence each CYP expression individually, the purpose of the present study was to measure the expression of 11 CYP genes and protein distribution in the liver of rats after spaceflight, using real-time polymerase chain reaction and immunohistochemistry, respectively. The gene and protein expression of stress-related proteins such as cold-inducible RNA binding protein (Cirp), heat shock protein 70 (HSP70), HSP90 and the p53 tumor suppressor gene, were also determined. CYP4A1and Cirp gene expression was significantly increased whereas HSP90 and p53 gene expression was significantly decreased in the flight group than in the ground control. Combined with histology, it is concluded that the effects of spaceflight on the liver may be similar to mild cold stress or fasting.

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“…Studies in rats during space flights, in which blood is possibly translocated (Hoffler 1971;Grounds 1979), have shown that the activity of many hepatic enzymes is profoundly modified (Abrahams et al 1983), Whether these effects are related to ANF remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Radioautographic localization of125I-atrial natriuretic fator (ANF) in rat tissues

et al. 1985

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Rats were injected either with synthetic 125I-Arg 101-Tyr 126 atrial natriuretic factor (ANF) or with 125I-ANF together with an excess of cold Arg 101-Tyr 126 ANF. Binding sites in various tissues were accepted depending on two criteria: displacement of radioactivity by cold ANF and absence of localization of silver grains on putative target cells in the presence of cold ANF. Binding sites were localized on zona glomerulosa cells and on adrenergic and noradrenergic cells of adrenal medulla, on hepatocytes, on the base of mature epithelial cells of villi in the small intestine, on smooth muscle cells of the muscularis layer of the colon and on the base of epithelial cells of the ciliary bodies. In addition, binding sites were localized in the vasculature of kidney, adrenal cortex, lung and liver. Binding sites were particularly numerous on renal glomerular endothelial cells. These results indicate that ANF may have important hemodynamic effects in kidney, lung, liver and adrenal cortex, may regulate water and ion transport in small intestine and ciliary bodies and may have metabolic effects in the liver. The presence of binding sites on the zona glomerulosa is in agreement with the important inhibitory effect of the peptide on aldosterone secretion.

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Biochemical Changes in Rat Liver after 18.5 Days of Spaceflight

Cited by 17 publications

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Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Analysis of gene and protein expression of cytochrome P450 and stress‐associated molecules in rat liver after spaceflight

Radioautographic localization of125I-atrial natriuretic fator (ANF) in rat tissues

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