Short-term treatment with hepatoselective NO donor V-PYRRO/NO improves blood flow in hepatic microcirculation in liver steatosis in mice.

Abstract

BACKGROUND:

The impairment of liver sinusoidal endothelial cells (LSECs) function and diminished nitric oxide (NO) production has been regarded as an important pathogenic factor in liver steatosis. Restoring NO-dependent function was shown to counteract liver steatosis, obesity, and insulin resistance. However, it is not known whether restored liver perfusion and improvement in hepatic blood flow contributes to the anti-steatotic effects of NO. Taking advantage of in vivo MRI, we have examined the effects of short-term treatment with the hepatoselective NO donor V-PYRRO/NO on hepatic microcirculation in advanced liver steatosis.

METHODS:

Male C57BL/6 mice fed for six months a high fat diet (HFD; 60 kcal% of fat) were treated for 3 weeks with V-PYRRO/NO (twice a day 5mg/kg b.w. ip). An MRI assessment of liver perfusion using the FAIR-EPI method and a portal vein blood flow using the FLASH method were performed. Blood biochemistry, glucose tolerance tests, a histological evaluation of the liver, and liver NO concentrations were also examined.

RESULTS:

Short-term treatment with V-PYRRO/NO releasing NO selectively in the liver improved liver perfusion and portal vein blood flow. This effect was associated with a slight improvement in glucose tolerance but there was no effect on liver steatosis, body weight, white adipose tissue mass, plasma lipid profile, or aminotransferase activity.

CONCLUSION:

Short-term treatment with V-PYRRO/NO-derived NO improves perfusion in hepatic microcirculation and this effect may also contribute to the anti-steatotic effects of hepatoselective NO donors linked previously to the modulation of glucose and lipid metabolism in the liver.

• Authors: Edyta Kus, Krzysztof Jasiński, Tomasz Skórka, Izabela Czyzynska-Cichon, Stefan Chlopicki
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 70 Issue 3 Pg. 463-469 (Jun 2018) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 29631249 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Chemical References

• Nitric Oxide Donors
• O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
• Pyrrolidines
• Nitric Oxide
• Transaminases

Topics

• Adipose Tissue, White (drug effects, metabolism)
• Animals
• Body Weight (drug effects)
• Fatty Liver (drug therapy, metabolism)
• Glucose Tolerance Test (methods)
• Lipid Metabolism (drug effects)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Microcirculation (drug effects)
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (pharmacology)
• Obesity (drug therapy, metabolism)
• Pyrrolidines (pharmacology)
• Regional Blood Flow (drug effects)
• Transaminases (metabolism)