Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide.

Affiliation

Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Sendai, 980-8578, Japan; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan. Electronic address: [Email]

Abstract

Systemic lupus erythematosus (SLE) increases the risk of preterm birth and preeclampsia (PE). The flares of SLE during pregnancy or after delivery are also problematic. We have previously demonstrated that nicotinamide (NAM), a non-teratogenic amide of vitamin B3, reduces inflammation and oxidative stress and improves PE-like phenotype and pregnancy outcomes in the mouse models of PE. The present study aimed to establish a model to investigate the pregnancy outcomes and flares of SLE in pregnant mice with SLE and to examine whether NAM is beneficial to pregnant mice with SLE. We used pregnant and non-pregnant lupus-prone MRL/lpr mice treated with or without a Toll-like receptor (TLR) ligand lipopolysaccharide (LPS) because TLR4 signaling reportedly exacerbates SLE and pregnancy; MRL/+ mice were used as controls. Blood pressure (BP) and urinary albumin excretion were increased only in the pregnant MRL/lpr-LPS mice. LPS together with pregnancy exacerbated glomerulonephritis, and the most severe inflammation was observed in the kidneys of the pregnant MRL/lpr-LPS mice. The shortening of pregnancy periods, increase in fetal demise percentage, and reduction in fetal weight were observed only in the pregnant MRL/lpr-LPS mice. NAM improved BP and kidney injury, prolonged pregnancy periods, and improved fetal growth in the pregnant MRL/lpr-LPS mice. The results suggest that SLE patients are prone to develop poor pregnancy outcome, and likely develop severe nephropathy and kidney inflammation. NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.

Keywords

Fetal growth restriction,Inflammation,Preterm birth,Systemic lupus erythematosus,Toll-like receptor 4,