Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD mimic compound.

Diabetes

Department of Pediatrics, Division of Immunogenetics, Diabetes Institute, University of Pittsburgh, School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Published: August 2002

The most commonly used technical approach to isolate human pancreatic islets intended for allotransplants generates a product that is hampered by mechanical and chemical insults, which dramatically reduce the mass of viable and functional transplantable cells. We tested a novel class of antioxidant chemical compounds (SOD mimics: AEOL10113 and AEOL10150) to protect human islets from oxidative stress in order to improve the preservation of the isolated tissue. Addition of SOD mimic in culture, after isolation, allowed for the survival of a significantly higher islet cell mass. Functional behavior and phenotypic cell characteristics of the SOD-treated islet preparations were preserved, as was the capacity to normalize diabetic mice, even when a marginal mass of islets was transplanted. The addition of SOD mimic during isolation, before culture, further reduced early cell loss. These results indicate that prompt interventions aimed at blocking oxidative stress can improve human islet survival, preserving a functional islet mass two- to threefold larger than the one usually obtained without adding any antioxidant compound. The ability to preserve functional islets without a dramatic loss represents a major advantage considering the scarce availability of islet tissue for clinical transplantation.

Download full-text PDF

Source
http://dx.doi.org/10.2337/diabetes.51.8.2561DOI Listing

Publication Analysis

Top Keywords

sod mimic
12
human islet
8
islet cell
8
oxidative stress
8
addition sod
8
islet
6
functional
5
mass
5
preservation human
4
cell
4

Similar Publications

Use of Intramolecular Quinol Redox Couples to Facilitate the Catalytic Transformation of O and O-Derived Species.

Acc Chem Res

January 2025

Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States.

ConspectusThe redox reactivity of transition metal centers can be augmented by nearby redox-active inorganic or organic moieties. In some cases, these functional groups can even allow a metal center to participate in reactions that were previously inaccessible to both the metal center and the functional group by themselves. Our research groups have been synthesizing and characterizing coordination complexes with polydentate quinol-containing ligands.

View Article and Find Full Text PDF

Superoxide dismutase enzymes are a major defense against superoxide, which is a potent reactive oxygen species. Misregulation of reactive oxygen species and subsequent neuronal damage are etiological hallmarks of neurodegenerative disease. Macrocyclic small molecules have offered inroads toward functional SOD1 mimics.

View Article and Find Full Text PDF

Free radicals such as superoxide are reactive species that, upon accumulation, lead to oxidative stress. The superoxide dismutase (SOD) enzyme mitigates this stress by converting superoxide into hydrogen peroxide and oxygen. However, the probable lack of SOD supplementation has driven the search for alternatives, with copper complexes emerging as promising candidates.

View Article and Find Full Text PDF

The disorder and heterogeneity of low-molecular-weight amyloid-beta oligomers (AβOs) underlie their participation in multiple modes of cellular dysfunction associated with the etiology of Alzheimer's disease (AD). The lack of specified conformational states in these species complicates efforts to select or design small molecules to targeting discrete pathogenic states. Furthermore, targeting AβOs alone may be therapeutically insufficient, as AD progresses as a multifactorial, self-amplifying cascade.

View Article and Find Full Text PDF

Drought stress significantly retards the plant production. Melatonin is a vital hormone, signaling molecule, and bio-regulator of diverse physiological growth and development processes. Its role in boosting agronomic traits under diverse stress conditions has received considerable attention.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!