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Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice.

Korolenko TA, Johnston TP, Dubrovina NI, Kisarova YA, Zhanaeva SY, Cherkanova MS, Filjushina EE, Alexeenko TV, Machova E, Zhukova NA - Interdiscip Toxicol (2013)

Bottom Line: A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration.The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration.In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia.

ABSTRACT
Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a 'plus-maze' test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

Influence of repeated P-407 administrations in mice on ultrastructure of liver (electron microscopy). A – Electron micrograph of liver cells (control). B – Electron micrograph of liver of mice with repeated P-407 administration after 24 h. In sinusoid lumen a large macrophage, filled by electron light granules. C – Liver cells in P-407-treated mice, 24 h. Macrophage overloaded by undigested material. D – Liver cell in P-407-treated mice, 24 h. Hepatocyte with “empty” zones in cytoplasma without subcellular structures. Denotes: Mph: macrophage, H: hepatocyte, S: sinusoid.
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Figure 0005: Influence of repeated P-407 administrations in mice on ultrastructure of liver (electron microscopy). A – Electron micrograph of liver cells (control). B – Electron micrograph of liver of mice with repeated P-407 administration after 24 h. In sinusoid lumen a large macrophage, filled by electron light granules. C – Liver cells in P-407-treated mice, 24 h. Macrophage overloaded by undigested material. D – Liver cell in P-407-treated mice, 24 h. Hepatocyte with “empty” zones in cytoplasma without subcellular structures. Denotes: Mph: macrophage, H: hepatocyte, S: sinusoid.

Mentions: Here, as well as in Figures 2–5, P-407 was administered to mice as an intraperitoneal (i.p.) injection, at a dose of 500 mg/kg twice per week over the course of one month according to Johnston (2004). The animals were assessed in the experiment 24 h and 5 days after the last dose of P-407 or saline solution (in the control group).


Effect of poloxamer 407 administration on the serum lipids profile, anxiety level and protease activity in the heart and liver of mice.

Korolenko TA, Johnston TP, Dubrovina NI, Kisarova YA, Zhanaeva SY, Cherkanova MS, Filjushina EE, Alexeenko TV, Machova E, Zhukova NA - Interdiscip Toxicol (2013)

Influence of repeated P-407 administrations in mice on ultrastructure of liver (electron microscopy). A – Electron micrograph of liver cells (control). B – Electron micrograph of liver of mice with repeated P-407 administration after 24 h. In sinusoid lumen a large macrophage, filled by electron light granules. C – Liver cells in P-407-treated mice, 24 h. Macrophage overloaded by undigested material. D – Liver cell in P-407-treated mice, 24 h. Hepatocyte with “empty” zones in cytoplasma without subcellular structures. Denotes: Mph: macrophage, H: hepatocyte, S: sinusoid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795317&req=5

Figure 0005: Influence of repeated P-407 administrations in mice on ultrastructure of liver (electron microscopy). A – Electron micrograph of liver cells (control). B – Electron micrograph of liver of mice with repeated P-407 administration after 24 h. In sinusoid lumen a large macrophage, filled by electron light granules. C – Liver cells in P-407-treated mice, 24 h. Macrophage overloaded by undigested material. D – Liver cell in P-407-treated mice, 24 h. Hepatocyte with “empty” zones in cytoplasma without subcellular structures. Denotes: Mph: macrophage, H: hepatocyte, S: sinusoid.
Mentions: Here, as well as in Figures 2–5, P-407 was administered to mice as an intraperitoneal (i.p.) injection, at a dose of 500 mg/kg twice per week over the course of one month according to Johnston (2004). The animals were assessed in the experiment 24 h and 5 days after the last dose of P-407 or saline solution (in the control group).

Bottom Line: A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration.The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration.In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, Novosibirsk, Russia.

ABSTRACT
Chronic administration of the poloxamer 407 (P-407), a block copolymer, to elevate serum lipids in mice is a well-established mouse model of hyperlipidemia and atherosclerosis. We tested the hypothesis that the activity of several types of proteases in heart and liver tissue is changed in the early stages of atherosclerosis development. Additionally, we evaluated whether increased serum lipids would induce anxiety in mice, as determined by using a 'plus-maze' test. The mice were administered P-407 by intraperitoneal injection twice a week for one month. P-407 administration to mice resulted in a marked increase in total serum cholesterol, atherogenic non-HDL-cholesterol, and especially in total triglycerides, and it also increased anxiety. Morphological changes observed in P-407-treated mice included contractile type changes in cardiomyocytes and foamy macrophages in liver. A significant increase of cysteine proteases cathepsin B and cathepsin L (at 24 h) and aspartate protease cathepsin D (at both 24 h and 5 days) was determined in heart tissue following P-407 administration. However, no changes were noted in heart matrix metalloproteinase activity. The activity of cysteine and aspartate proteases was significantly increased in liver at both 24 hours and 5 days after P-407 administration. In conclusion, administration of P-407 to mice for one month resulted in increased anxiety, and more importantly, there was an increase in the activity of heart and liver proteases secondary to sustained dyslipidemia. It is suggested that heart and liver cysteine and aspartate proteases may represent potential therapeutic targets in the early stages of atherosclerosis.

No MeSH data available.


Related in: MedlinePlus