Psoriasis-like inflammation leads to renal dysfunction via upregulation of NADPH oxidases and inducible nitric oxide synthase.

Abstract

Psoriatic patients have systemic inflammation as well as oxidative stress, which are associated with cardiovascular disorders such as atherosclerosis, hypertension myocardial infarction, and stroke. Psoriasis has also been shown to be associated with kidney disease in several studies. Both disorders also have strong component of oxidative stress which usually emanates from NADPH oxidases (NOXs) and inducible nitric oxide synthase (iNOS). However, whether psoriatic inflammation leads to renal oxidative stress and dysfunction remains unexplored. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on kidney function and inflammation in a murine model. Mice were topically applied IMQ followed by various analyses in kidney/blood related to inflammation and kidney function. Psoriatic inflammation in mice was associated with kidney dysfunction as reflected by increased serum creatinine and blood urea nitrogen. Kidney dysfunction was paralleled by upregulation of ROS generating enzymes such as NOX2, NOX4 and iNOS with concomitant oxidative stress. Treatment either with general antioxidant, N-acetyl cysteine or NOX/iNOS inhibitors led to improvement of IMQ-induced renal dysfunction and oxidative stress. On the contrary, buthionine sulfoximine, oxidant inducer further aggravated IMQ-induced renal impairment and oxidant-antioxidant imbalance. Our data suggest that psoriatic inflammation causes kidney dysfunction where NOXs and iNOS play important roles. Treatment with antioxidants may be considered as adjunct therapy in psoriatic patients with kidney disease.

• Authors: Naif O Al-Harbi, Ahmed Nadeem, Mushtaq A Ansari, Mohammed M Al-Harbi, Moureq R Alotaibi, Abdulaziz M S AlSaad, Sheikh F Ahmad
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 46 Pg. 1-8 (May 2017) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 28249219 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Aminoquinolines
• Antioxidants
• Membrane Glycoproteins
• Buthionine Sulfoximine
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cybb protein, mouse
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, mouse
• Imiquimod
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Aminoquinolines
• Animals
• Antioxidants (therapeutic use)
• Buthionine Sulfoximine (administration & dosage)
• Disease Models, Animal
• Humans
• Imiquimod
• Inflammation (chemically induced, drug therapy, immunology)
• Kidney (metabolism, pathology)
• Kidney Diseases (chemically induced, drug therapy, immunology)
• Male
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Oxidative Stress (drug effects)
• Psoriasis (chemically induced, drug therapy, immunology)