iNOS, eNOS, and XOR involvement in hyperglycaemia-induced kidney injury in rats with streptozotocin diabetes mellitus

Jelizaveta Sokolovska; Sergejs Isajevs; Olga Sugoka; Larisa Baumane; Darja Isajeva; Jelena Sharipova; Ivars Kalvinsh; Nikolajs Sjakste

doi:10.1530/endoabs.32.P410

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Endocrine Abstracts (2013) 32 P410 | DOI: 10.1530/endoabs.32.P410

ECE2013 Poster Presentations Diabetes (151 abstracts)

iNOS, eNOS, and XOR involvement in hyperglycaemia-induced kidney injury in rats with streptozotocin diabetes mellitus

Jelizaveta Sokolovska ^1, , Sergejs Isajevs ¹ , Olga Sugoka ¹ , Larisa Baumane ² , Darja Isajeva ¹ , Jelena Sharipova ¹ , Ivars Kalvinsh ² & Nikolajs Sjakste ^1,

Err

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

Introduction: Diabetic nephropathy is a major complication of diabetes mellitus. Involvement of abnormal nitric oxide (NO) production, both via nitric oxide synthase (NOS) dependent and independent pathways (for example, xantine oxoridoreductase (XOR)) has been discussed. New compounds to treat diabetic nephropathy are searched intensively, some novel dihydropirine class drugs (DHP) have been proposed for this purpose.

Aim: To study the changes in NO concentration and expression of NOS isoforms and XOR in kidneys of diabetic rats in the early phase of diabetic nephropathy and under effect of DHP etaftorone.

Methods: Diabetes mellitus in rats was induced by streptozotocin (STZ) 50 mg/kg, i.v., after a week rats were treated by etaftorone 0.5 mg/kg per os for three consecutive days. Production of NO in kidneys was monitored by means of ESP spectroscopy. iNOS, eNOS, and XOR mRNA and protein expression in kidneys were detected by qRT-PCR and immunohistochemistry correspondingly.

Results: Development of STZ DM was followed by a significant increase of NO production in the kidneys, which could be attenuated by etaftoron (control: 2.64±0.97 ng/g tissue, STZ: 15.04±2.04 ng/g tissue, and STZ+etaftoron: 5.52±1.089 ng/g tissue). In STZ group, XOR expression was increased (STZ 27±7 vs control 8±2 cells/mm²; P=0.002.), and normalized by etaftoron (STZ+etaftoron: 9±3 cells/mm² vs STZ: 27±7 cells/mm²; P=0.0006). Similar, kidney iNOS protein expression increased in STZ group and was normalized by etaftoron (STZ: 29±15 cells/mm² vs control 11±4 cells/mm²; P=0.004; STZ+etaftoron 13±6 cells/mm², P=0.04 vs STZ). eNOS-expression decreased in diabetic rat kidneys, etaftoron attenuated the decrease.

Conclusions: Diabetic state provokes increase of NO production in rat kidneys shortly after diabetes induction and seems to be associated with hyperexpression of iNOS and XOR. These changes can be attenuated by DHP class drug etaftoron.