We investigated the detrimental effects of diabetes on myocardium of pregestational streptozotocin (STZ)-diabetic mother rats and their neonates via evaluations of oxidative redox, inflammatory and apoptotic pathways, also aiming to characterize whether calcitriol and/or pomegranate peel extract confer myocardial protection in hyperglycaemic dams and their foetuses via modulation of the Raf/MEK/ERK cascade. Sixty Sprague-Dawley female rats were randomized into five groups (N = 12): control, diabetic, diabetic treated with calcitriol and/or pomegranate peel extract (PPE), and mated with non-diabetic healthy males. After confirmation of pregnancy, treatments were kept until gestational day (E-18). Serum and cardiac tissues of mothers and foetuses were collected and processed for biochemical, histopathological, and molecular assessments. We observed that, compared to the control, diabetic mothers showed dramatically increased hyperglycaemia and hyperlipidaemia associated with decreased myocardial functions and disrupted maternal performance. Also, diabetic mothers and their neonates exhibited elevated levels of myocardial injury (troponin I, endothelin 1, creatine kinase-MB, lactate dehydrogenase), with increased pro-inflammatory cytokines (interleukin 1, interleukin 1β, transforming growth factor β) and oxidative redox. Concurrently, the MAPK pathway was significantly down-regulated with increased myocardial apoptotic activity. Furthermore, mRNA expression of angiogenic and fibrotic markers was significantly increased. Paradoxically, calcitriol and/or pomegranate peel extract alleviated these diabetic myocardial insults and normalized the aforementioned assayed parameters. Our findings hypothesized that calcitriol and/or pomegranate peel extract exerted cardioameliorative impacts due to their unique anti-oxidative and anti-inflammatory properties, and thus may be a promising treatment that directly targets the secondary myocardial complications of diabetes in dams and their offspring.
- MeSH
- apoptóza * účinky léků MeSH
- biologické markery metabolismus MeSH
- cytokiny metabolismus MeSH
- experimentální diabetes mellitus komplikace farmakoterapie patologie MeSH
- fibróza MeSH
- fosforylace účinky léků MeSH
- fyziologická neovaskularizace účinky léků MeSH
- kalcitriol terapeutické užití MeSH
- kardiomyopatie komplikace farmakoterapie patologie MeSH
- kaspasa 3 metabolismus MeSH
- MAP kinasový signální systém * účinky léků MeSH
- marhaník chemie MeSH
- mitogenem aktivované proteinkinasy kinas metabolismus MeSH
- myokard patologie MeSH
- novorozená zvířata MeSH
- oxidační stres účinky léků MeSH
- plod patologie MeSH
- poškození DNA MeSH
- potkani Sprague-Dawley MeSH
- raf kinasy metabolismus MeSH
- rostlinné extrakty terapeutické užití MeSH
- rozmnožování MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- streptozocin MeSH
- upregulace účinky léků MeSH
- vitamin D farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
