Correction of Aberrant NADPH Oxidase Activity in Blood-Derived Mononuclear Cells from Type II Diabetes Mellitus Patients by a Naturally Fermented Papaya Preparation

Abstract

Supplementation of standardized fermented papaya preparation (FPP) to adult diabetic mice improves dermal wound healing outcomes. Peripheral blood mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a compromised respiratory burst activity resulting in increased risk of infections for the diabetic patients. Aims: The objectives of the current study were to determine the effect of FPP supplementation on human diabetic PBMC respiratory burst activity and to understand underlying mechanisms of such action of FPP. Results: When stimulated with phorbol 12-myristate 13-acetate, the production of reactive oxygen species by T2DM PBMC was markedly compromised compared to that of the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA expression of Rac2 was potently upregulated after FPP supplemention. The proximal human Rac2 gene promoter is G-C rich and contains consensus binding sites for Sp1 and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity, the Sp1 DNA binding activity was significantly upregulated in PBMC after treatment of the cells with FPP. Innovation: This work provided first evidence that compromised respiratory burst performance of T2DM PBMC may be corrected by a nutritional supplement. Conclusion: FPP can correct respiratory burst performance of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP supplementation in diabetic patients are warranted. Antioxid. Redox Signal. 17, 485-491.

Does Oral Supplementation of a Fermented Papaya Preparation Correct Respiratory Burst Function of Innate Immune Cells in Type 2 Diabetes Mellitus Patients?

“…Recently, our laboratory reported the first experimental evidence demonstrating that FPP may improve diabetic wound outcomes by specifically influencing the response of wound-site macrophages and the subsequent angiogenic response (3). Furthermore, our ex vivo work demonstrated that FPP may correct deficiencies in respiratory burst capacity of peripheral blood mononuclear cells (PBMC) of type 2 diabetes mellitus (T2D) patients (6). The objectives of this study Innovation T2D patients are known to suffer from compromised respiratory burst function, making them vulnerable to infection-related complications.…”

“…FPP is safe for T2D patient consumption FPP possesses potent antioxidant activity (1). Our studies with T2D subjects demonstrated a beneficial effect of the supplement ex vivo on monocyte respiratory burst activity (6). This study was performed to determine whether FPP can confer a similar beneficial effect on monocytes when supplemented orally to T2D patients.…”

Modulation of NADPH oxidase activity by known uraemic retention solutes

“…Peripheral blood mononuclear cells are established sources for determination of NADPH oxidase activity [27,28]. Blood from healthy volunteers was centrifuged at 150 9 g for 10 min at 20°C.…”

“…The NADPH oxidase was obtained from the cell membranes of the mononuclear leucocytes after 3 freeze-thawing cycles. Peripheral blood mononuclear cells are established sources for determination of NADPH oxidase activity [27,28].…”

Mitochondria in monocytes and macrophages-implications for translational and basic research

“…This is important because both elevated oxidative stress and mitochondrial dysfunction can lead to increased apoptosis in CKD monocytes (Dounousi et al, 2012) and tissues. Interestingly, the oxidative burst, which is necessary for innate immunity, is suppressed in diabetics suggesting that decreased oxidative burst activity could be related to the severity of renal dysfunction (Dickerson et al, 2012), a suppressed immune response, accumulation of damaged monocytes, and disease pathology. It is clear that mitochondrial homeostasis and gene expression is perturbed in immune cells during diabetes and is likely a critical factor in the development of atherosclerosis in these patients.…”