Hyperpolarized 13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) ¹³C dehydroascorbate (DHA) and ¹³C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham‐operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP ¹³C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP ¹³C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP ¹³C lactate/pyruvate ratio at day 7 compared with baseline, although the ¹³C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham‐operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP ¹³C MRS for the non‐invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.     

Immunoregulation of Inflammatory and Inhibitory Cytokines by Vitamin D3 in Patients with Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of vitamin D3 in patients with IBD exerts both direct and indirect regulatory roles on the naïve T cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of vitamin D3 on naïve T cells result in the proliferation of more regulatory T cells and inhibitory cytokines such as IL‐4, IL‐10 and IL‐5. The binding of vitamin D to dendritic cells (DCs) through vitamin D receptors inhibits the action of IL‐12 on DCs, resulting in the downregulation of Th1 and Th17. On the other hand, this interaction favours Th2 and Treg upregulation and facilitates the maintenance of immune homoeostasis between inflammatory and inhibitory cytokines which is essentially significant in the management of patients with IBD. The aim of this review was to explore the current and mounting scientific evidence on the roles of vitamin D3 in immunoregulation of inflammatory and inhibitory cytokines in patients with IBDs. An extensive literature search was conducted using keywords such as Vitamin D3*, IBD*, inflammatory cytokines*, inhibitory cytokines*, naïve‐T‐cells* and antigen presenting cells* through PubMed, SCOPUS and MEDLINE search engines. The results of the accumulated bodies of research that have been conducted demonstrate that vitamin D3 plays a major role not only in the immunoregulation of cytokines involved in the pathogenesis of IBDs but also in many other inflammatory disorders.