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Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice
A K Zhanataev1, E A Anisina2, A V Kulakova2
1V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia. pharmacol@yandex.ru.
Abstract:
Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations. The level of atypical DNA comets on day 21 after a single administration of streptozotocin increased in the kidneys, but not in the brain, testes, and pancreas. Real-time PCR revealed mtDNA damage in the liver, kidney, and pancreatic cells of mice with streptozotocin-induced diabetes. Thus, these animal models were found to reproduce pathognomic signs of diabetes, hyperglycemia, and nDNA damage; mtDNA damage was also detected.
Insights
This study shows that streptozotocin-induced diabetes in mice causes both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage. These animal models effectively replicate key diabetes signs, including hyperglycemia and DNA damage in various organs.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Diabetes mellitus is a complex metabolic disorder characterized by hyperglycemia.
- DNA damage, affecting both nuclear and mitochondrial genomes, is implicated in diabetic complications.
- Streptozotocin is a commonly used agent to induce diabetes in animal models for research purposes.
Purpose of the Study:
- To investigate nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage in a mouse model of streptozotocin-induced diabetes mellitus.
- To evaluate the efficacy of different streptozotocin administration protocols in inducing diabetic phenotypes and DNA damage.
- To assess the organ-specific distribution of DNA damage in diabetic mice.
Main Methods:
- Induction of diabetes in male BALB/c mice using single or repeated streptozotocin injections.
- Assessment of hyperglycemia at various time points post-induction.
- Quantification of nDNA damage using the comet DNA assay.
- Measurement of mtDNA damage using real-time PCR.
Main Results:
- Both single and repeated streptozotocin administration successfully induced severe hyperglycemia.
- Increased nDNA damage and atypical DNA comets were observed in the liver of diabetic mice.
- Significant mtDNA damage was detected in liver, kidney, and pancreatic cells of diabetic mice.
- nDNA damage was also noted in the kidneys, but not in the brain, testes, or pancreas.
Conclusions:
- The streptozotocin-induced diabetes mouse model accurately reproduces key pathological features of diabetes, including hyperglycemia and nDNA damage.
- This model demonstrates significant mtDNA damage in multiple organs, highlighting its utility for studying diabetes-related genotoxicity.
- The findings underscore the importance of evaluating both nDNA and mtDNA integrity in the context of diabetes research.
