Oxidative stress and inflammatory markers in streptozotocin-induced acute and subacute toxicity response

Abstract

Streptozotocin (STZ) is used as a diabetes-inducing agent in experimental animal studies. However, it is known that STZ-induced diabetic animals show significant increases in oxidative stress parameters and neurodegeneration besides their blood glucose level. In this study, the acute and subacute toxic effects of STZ on the liver, sciatic nerve, and brain tissues were investigated in vivo rat model. Sprague-Dawley rats were divided into two groups; while 50 mg/kg STZ was administered ip to the STZ group, only saline was administered to the control group. After STZ administration, three units (100 U/mL) of subcutaneous insulin glargine were applied daily to prevent the formation of diabetes. At 24 h, 1,2, and 4 weeks after applications, rats from each group were sacrificed and tissues were removed under anesthesia. At the end of the study, compared to the control, a significant decrease in SOD and GST activity and an increase in lipid peroxidation were detected in the liver and sciatic tissues of rats in the STZ-treated group in the first 24h. Considering the TUNEL, NFκB, and NOS2 expressions, it was noted that while the effects of STZ on the liver were observed in the acute stage (24h), it had subacute effects on the brain. When apoptosis-related gene expression (Bcl-2, Bax, CASP3, CASP8, CASP9, TNF-α) and immunohistochemistry were evaluated, the apoptotic effect of STZ was observed mostly in sciatic nerve tissues. Within the scope of the study, it was revealed that STZ did not only show selective toxicity to pancreatic β cells but also very toxic to other tissues and organs.

Keywords:

• Streptozotocin
• toxicity
• apoptosis
• rt-pcr
• ımmunohistochemistry

Authors’ contribution

NUKY and OE designed the study. ES, CKK and GY performed the in vivo experiments. ES and AB performed the RT-PCR analyses. MD performed the enzymatic analysis. GY and AB prepared the histological and immunohistochemical slides. AY performed the histological and immunohistochemical imaging, interpreted data and prepared figures. NUKY performed the statistical analysis and interpreted data. CKK and NUKY wrote the manuscript. All authors reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Additional information

Funding

This study was supported by The Aliye Uster Foundation and Ege University, Scientific Research Foundation (BAP Project number: 15-FBE-003).