Endocrine Abstracts (2012) 29 P618

Changes of NO concentration in the cause of streptozotocin diabetes mellitus and under action of different NOS inhibitors in streptozotocin rats

J. Sokolovska1,2, J. Sharipova1, L. Lauberte1, L. Baumane1, I. Kalvins1 & N. Sjakste1,2


1Latvian Institute of Organic Synthesis, Riga, Latvia; 2University of Latvia, Riga, Latvia.


Background: Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic action of nitric oxide (NO) is responsible to a large extent for development of complications of the disease. Thus modification of NO production in DM patients appears to be an option for treatment of DM complications.

Objective: To study changes in NO concentration in diabetic rats after administration of different compounds with potential influence of NO production: iNOS inhibitors aminoguanidine and 1400 W, specific inhibitor of Kupffer cells GdCl3 and xantine oxidase inhibitor allopurinole.

Methods: Severe diabetes mellitus in rats was induced by single injection of streptozotocin (STZ) 50 mg/kg, i.v., after 1 week of diabetic state compounds of interest were administered. Production of NO was monitored by means of ESP spectroscopy of Fe–DETC–NO complex in brain cortex, cerebellum, liver, kidneys, whole blood, skeletal muscle, subcutaneous fat and aorta.

Results: Development of STZ DM was followed by increase of NO production in the liver from 45.39±5.93 to 101.81±12.12 ng/g tissue, kidneys (from 2.64±0.97 to 15.04±2.04 ng/g tissue), blood (from 29.36±2.15 to 41.62±3.93 ng/g tissue), muscles (from 7.82±1.87 to 12.65±0.87 ng/g tissue), aorta (from 14.4±0.2 to 42.2±4.2 ng/g). In adipose tissue NO production decreased from 34.00±3.68 to 18.56±1.81 ng/g tissue. In diabetic rats, 1400 W decreased NO concentration in liver, kidney, muscle, whole blood, fat and aorta, aminoguanidine – in all studies organs except brain cortex, allopurinol – in kidneys, muscle, aorta and fat.

Conclusions: Diabetic state provokes increase of NO production in rats. iNOS inhibitors aminoguanidine and 1400 W, as well as allopurinole attenuated increase of NO concentration in most organs studied. Modification of NO production could be useful in prevention of some diabetic complications.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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