Homoarginine ameliorates diabetic nephropathy independent of nitric oxide synthase-3.

Abstract

Recently we showed that homoarginine supplementation confers kidney protection in diabetic mouse models. In this study we tested whether the protective effect of homoarginine is nitric oxide synthase-3 (NOS3)-independent in diabetic nephropathy (DN). Experiments were conducted in NOS3 deficient (NOS3-/- ) mice and their wild type littermate using multiple low doses of vehicle or streptozotocin and treated with homoarginine via drinking water for 24 weeks. Homoarginine supplementation for 24 weeks in diabetic NOS3-/- mice significantly attenuated albuminuria, increased blood urea nitrogen, histopathological changes and kidney fibrosis, kidney fibrotic markers, and kidney macrophage recruitment compared with vehicle-treated diabetic NOS3-/- mice. Furthermore, homoarginine supplementation restored kidney mitochondrial function following diabetes. Importantly, there were no significant changes in kidney NOS1 or NOS2 mRNA expression between all groups. In addition, homoarginine supplementation improved cardiac function and reduced cardiac fibrosis following diabetes. These data demonstrate that the protective effect of homoarginine is independent of NOS3, which will ultimately change our understanding of the mechanism(s) by which homoarginine induce renal and cardiac protection in DN. Homoarginine protective effect in DN could be mediated via improving mitochondrial function.

• Authors: Michael D Wetzel, Kristen Stanley, Soumya Maity, Muniswamy Madesh, Jean C Bopassa, Alaa S Awad
• Journal: Physiological reports (Physiol Rep) Vol. 9 Issue 5 Pg. e14766 (03 2021) ISSN: 2051-817X [Electronic] United States
• PMID: 33713581 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Homoarginine
• Streptozocin
• Nitric Oxide Synthase Type III
• Nos3 protein, mouse

Topics

• Albuminuria (metabolism)
• Animals
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetic Nephropathies (drug therapy, metabolism)
• Homoarginine (metabolism, pharmacology)
• Kidney (drug effects, metabolism)
• Macrophages (metabolism)
• Mice, Inbred C57BL
• Mice, Knockout
• Nitric Oxide Synthase Type III (drug effects)
• Oxidative Stress (drug effects)
• Streptozocin (pharmacology)
• Mice