Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury.

Abstract

BACKGROUND AND PURPOSE:

The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects.

METHODS:

Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons.

RESULTS:

Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain.

CONCLUSIONS:

Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.

• Authors: Keun-Hwa Jung, Kon Chu, Song-Yi Ko, Soon-Tae Lee, Dong-In Sinn, Dong-Kyu Park, Jeong-Min Kim, Eun-Cheol Song, Manho Kim, Jae-Kyu Roh
• Journal: Stroke (Stroke) Vol. 37 Issue 11 Pg. 2744-50 (Nov 2006) ISSN: 1524-4628 [Electronic] United States
• PMID: 17008610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Sodium Nitrite

Topics

• Animals
• Brain (drug effects, pathology)
• Infusions, Intravenous
• Male
• Neuroprotective Agents (administration & dosage)
• Rats
• Reperfusion Injury (drug therapy, pathology, prevention & control)
• Sodium Nitrite (administration & dosage)
• Time Factors