Thymulin and peroxiredoxin 6 have protective effects against streptozotocin-induced type 1 diabetes in mice

Abstract

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F β-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.

Role of Innate Immunity and Oxidative Stress in the Development of Type 1 Diabetes Mellitus. Peroxiredoxin 6 as a New Anti-Diabetic Agent

“…Our studies with streptozotocin induced murine T1D model also revealed the Prdx6 associated protective effect [82]. Owing to the clinical application of STZ as a chemotherapeutic agent details regarding its mode of action are known [83].…”

“…It may be assumed that Hsp90α could serve as one of the T1D markers. Abrupt upregulation of the expression of Hsp90α was observed in the RIN m5F beta cells in in vitro settings [92], as well as in immune cells from the mice with STZ induced T1D [82]. In the process Prdx6 fully normalized the level of Hsp90α in immune and beta cells.…”

“…Despite the fact that ROS formation in the STZ induced diabetes plays no central role, the data undoubt edly prove that Prdx6 displays protective effects. In par ticular, Prdx6 protects pancreatic beta cells from death, reduces hyperglycemia, normalizes serum TNF α level, activity of NF κB pathway, and Hsp90 cell level in the mice with STZ induced T1D [82]. It is plausible that the efficacy of Prdx6 could be explained by not only by antioxidant properties, but also by its phospholipase activity.…”

Identification of Markers for Diagnosis and Treatment of Diabetic Kidney Disease Based on the Ferroptosis and Immune

“…It increases the expression of SLC7A11 and GPX4 and inhibits ferroptosis. Interestingly, PRDX6 reduced the activation of plasma NF- κ B and TNF- α levels in diabetic mice [ 31 ]. These results strongly suggest that PRDX6 can improve renal function by inhibiting ferroptosis, which may be closely related to improving inflammatory response.…”

The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus

“…Interestingly, the insulin-stimulating activity of Prx6 in vitro was detected both when RIN-m5F β-cells were cultivated under normal conditions and under stressful conditions, inducing cell death [99]. In an alloxan-or streptozotocin-induced mouse model of diabetes, intravenous administration of recombinant Prdx6 prevented hyperglycemia, reduced mortality, restored the plasma cytokine profile, and reduced β-cell destruction in the islets of Langerhans in the mouse pancreas [100][101][102].…”