scholarly journals Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Huang ◽  
Diogo Ladeiras ◽  
Yi Yu ◽  
Xiu-Fen Ming ◽  
Zhihong Yang
Keyword(s):  
Nitric Oxide ◽  
Functional Decline ◽  
Renal Diseases ◽  
Acid Diet ◽  
Tnf Α ◽  
High Amino Acid ◽  
Arginase Ii ◽  
Underlying Mechanisms ◽  
Arginine Supplementation

The impaired L-arginine/nitric oxide pathway is a well-recognized mechanism for cardiovascular and renal diseases with aging. Therefore, supplementation of L-arginine is widely proposed to boost health or as adjunct therapy for the patients. However, clinical data, show adverse effects and even enhanced mortality in patients receiving long-term L-arginine supplementation. The effects of long-term L-arginine supplementation on kidney aging and the underlying mechanisms remain elusive. Moreover, high protein and high amino acid diet has been thought detrimental for kidney. We therefore investigated effects of chronic dietary L-arginine supplementation on kidney aging. In both young (4 months) and old (18–24 months) mice, animals either receive standard chow containing 0.65% L-arginine or diet supplemented with L-arginine to 2.46% for 16 weeks. Inflammation and fibrosis markers and albuminuria are then analyzed. Age-associated increases in tnf-α, il-1β, and il-6, vcam-1, icam-1, mcp1, inos, and macrophage infiltration, collagen expression, and S6K1 activation are observed, which is not favorably affected, but rather further enhanced, by L-arginine supplementation. Importantly, L-arginine supplementation further enhances age-associated albuminuria and mortality particularly in females, accompanied by elevated renal arginase-II (Arg-II) levels. The enhanced albuminuria by L-arginine supplementation in aging is not protected in Arg-II−/− mice. In contrast, L-arginine supplementation increases ROS and decreases nitric oxide production in old mouse aortas, which is reduced in Arg-II−/− mice. The results do not support benefits of long-term L-arginine supplementation. It rather accelerates functional decline of kidney and vasculature in aging. Thus, the long-term dietary L-arginine supplementation should be avoided particularly in elderly population.

Autoimmune-mediated renal disease and hypertension

2021 ◽  
Vol 135 (17) ◽  
pp. 2165-2196
Author(s):  
Erika I. Boesen ◽  
Rahul M. Kakalij
Keyword(s):  
Renal Disease ◽  
Lupus Erythematosus ◽  
Functional Decline ◽  
Immunoglobulin A ◽  
Renal Diseases ◽  
Therapeutic Approaches ◽  
The Past ◽  
Current State ◽  
Underlying Mechanisms ◽  
Disease Specific

Abstract Hypertension is a major risk factor for cardiovascular disease, chronic kidney disease (CKD), and mortality. Troublingly, hypertension is highly prevalent in patients with autoimmune renal disease and hastens renal functional decline. Although progress has been made over the past two decades in understanding the inflammatory contributions to essential hypertension more broadly, the mechanisms active in autoimmune-mediated renal diseases remain grossly understudied. This Review provides an overview of the pathogenesis of each of the major autoimmune diseases affecting the kidney that are associated with hypertension, and describes the current state of knowledge regarding hypertension in these diseases and their management. Specifically, discussion focuses on Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN), Immunoglobulin A (IgA) Nephropathy, Idiopathic Membranous Nephropathy (IMN), Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated glomerulonephritis, and Thrombotic Thrombocytopenic Purpura (TTP). A summary of disease-specific animal models found to exhibit hypertension is also included to highlight opportunities for much needed further investigation of underlying mechanisms and novel therapeutic approaches.

Factors mediating the hemodynamic effects of tumor necrosis factor-α in portal hypertensive rats

1999 ◽  
Vol 276 (3) ◽  
pp. G687-G693 ◽  
Author(s):  
Javier Muñoz ◽  
Agustín Albillos ◽  
María Pérez-Páramo ◽  
Irma Rossi ◽  
Melchor Alvarez-Mon
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Portal Pressure ◽  
Systemic Resistance ◽  
Short Term ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the hyperdynamic circulatory state of portal hypertension. Recent evidence also indicates that increased tumor necrosis factor-α (TNF-α) production is involved in the pathogenesis of this hemodynamic abnormality. This study was aimed at investigating in rats with portal vein stenosis (PVS) the effects on splanchnic hemodynamics of blocking circulating TNF-α and the factors mediating the vascular action of this cytokine in this setting. Anti-TNF-α polyclonal antibodies or placebo was injected into rats ( n = 96) before and 4 days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS (long-term inhibition). Short-term TNF-α inhibition reduced portal venous inflow and cardiac index and increased splanchnic and systemic resistance. Portal pressure was unchanged, but portal-systemic shunting was decreased. After long-term TNF-α inhibition, portal venous inflow and portal pressure were unchanged, but arterial pressure and systemic resistance rose significantly. Anti-TNF-α PVS rats exhibited lower increments of systemic resistance after N ω-nitro-l-arginine methyl ester and indomethacin administration and lower serum levels of TNF-α, nitrates-nitrites, and 6-keto-PGF1α, both over the short and the long term. Serum glucagon levels rose after long-term inhibition. In conclusion, the specific role played by TNF-α in the development of the hyperdynamic state of portal hypertension appears to be mainly mediated through an increased release of nitric oxide and prostacyclin. Maintenance of the splanchnic hyperemia after long-term TNF-α inhibition could be due to a compensatory release of glucagon.

Arsenic trioxide: a promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice

Blood ◽  
2006 ◽  
Vol 108 (13) ◽  
pp. 3967-3975 ◽  
Author(s):  
Pierre Bobé ◽  
Danielle Bonardelle ◽  
Karim Benihoud ◽  
Paule Opolon ◽  
Mounira K. Chelbi-Alix
Keyword(s):  
Nitric Oxide ◽  
Arsenic Trioxide ◽  
Therapeutic Agent ◽  
Fas Ligand ◽  
Survival Rates ◽  
Tnf Α ◽  
Activated T Lymphocytes ◽  
Ifn Γ ◽  
Kidney Lesions

Abstract MRL/lpr mice develop a human lupuslike syndrome and, as in autoimmune lymphoproliferative syndrome (ALPS), massive lymphoproliferation due to inactivation of Fas-mediated apoptosis. Presently, no effective therapy exists for ALPS, and long term, therapies for lupus are hazardous. We show herein that arsenic trioxide (As2O3) is able to achieve quasi-total regression of antibody- and cell-mediated manifestations in MRL/lpr mice. As2O3 activated caspases and eliminated the activated T lymphocytes responsible for lymphoproliferation and skin, lung, and kidney lesions, leading to significantly prolonged survival rates. This treatment also markedly reduced anti-DNA autoantibody, rheumatoid factor, IL-18, IFN-γ, nitric oxide metabolite, TNF-α, Fas ligand, and IL-10 levels and immune-complex deposits in glomeruli. As2O3 restored cellular reduced glutathione levels, thereby limiting the toxic effect of nitric oxide, which is overproduced in MRL/lpr mice. Furthermore, As2O3 protected young animals against developing the syndrome and induced almost total disease disappearance in older affected mice, thereby demonstrating that it is a novel promising therapeutic agent for autoimmune diseases.

scholarly journals Secukinumab Attenuates Neuroinflammation and Neurobehavior Defect via PKCβ /ERK/NF-κB Pathway in a Rat Model of GMH

2021 ◽  
Author(s):  
Shengpeng Liu ◽  
Shuixiang Deng ◽  
Yan Ding ◽  
Jerry J. Flores ◽  
Xiaoli Zhang ◽  
...  
Keyword(s):  
Neurological Deficits ◽  
Clinical Event ◽  
Sprague Dawley ◽  
Neurological Outcomes ◽  
Beneficial Effects ◽  
Rat Pups ◽  
Tnf Α ◽  
Short And Long Term ◽  
Underlying Mechanisms

Abstract AimsGerminal matrix hemorrhage (GMH) is a disastrous clinical event for newborns. Neuroinflammation plays an important role in the development of neurological deficits after GMH. The purpose of this study is to investigate the anti-inflammatory role of secukinumab after GMH and its underlying mechanisms involving PKCβ/ERK/NF-κB signaling pathway.MethodsA total of 154 Sprague-Dawley P7 rat pups were used. GMH was induced by intraparenchymal injection of bacterial collagenase. Secukinumab was administered intranasally post-GMH. PKCβ activator PMA and p-ERK activator Ceramide C6 were administered intracerebroventricularly at 24h prior to GMH induction, respectively. Neurobehavioral tests, Western blot and immunohistochemistry were used to evaluate the efficacy of secukinumab in both short-term and long-term studies.ResultsEndogenous IL-17A, IL-17RA, PKCβ and p-ERK were increased after GMH. Secukinumab treatment improved short- and long-term neurological outcomes, reduced the expression of MPO and Iba-1 in the perihematoma area, and inhibited the expression of proinflammatory factors, such as NF-κB, IL-1β, TNF-α and IL-6. Additionally, PMA and ceramide C6 abolished the beneficial effects of secukinumab. ConclusionSecukinumab treatment suppressed neuroinflammation and attenuated neurological deficits after GMH, which was mediated through the downregulation of the PKCβ/ERK/NF-κB pathway. Secukinumab treatment may provide a promising therapeutic strategy for GMH patients.

Hydrogen Sulfide in Physiological and Pathological Mechanisms in Brain

2018 ◽  
Vol 17 (9) ◽  
pp. 654-670 ◽  
Author(s):  
Mohit Kumar ◽  
Rajat Sandhir
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Hydrogen Sulfide ◽  
Neurodegenerative Disorders ◽  
Neurological Disorders ◽  
Scientific Community ◽  
Molecular Targets ◽  
Long Term Potentiation ◽  
Term Potentiation

Background & Objective: Hydrogen sulfide [H2S] has been widely known as a toxic gas for more than 300 years in the scientific community. However, the understanding about this small molecule has changed after the discovery of involvement of H2S in physiological and pathological mechanisms in brain. H2S is a third gasotransmitter and neuromodulator after carbon monoxide [CO] and nitric oxide [NO]. H2S plays an important role in memory and cognition by regulating long-term potentiation [LTP] and calcium homeostasis in neuronal cells. The disturbances in endogenous H2S levels and trans-sulfuration pathway have been implicated in neurodegenerative disorders like Alzheimer’s disease, Parkinson disease, stroke and traumatic brain injury. According to the results obtained from various studies, H2S not only behaves as neuromodulator but also is a potent antioxidant, anti-inflammatory and anti-apoptotic molecule suggesting its neuroprotective potential. Conclusion: Recently, there is an increased interest in developing H2S releasing pharmaceuticals to target various neurological disorders. This review covers the information about the involvement of H2S in neurodegenerative diseases, its molecular targets and its role as potential therapeutic molecule.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

2019 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Mahsa Hatami ◽  
Mina Abdolahi ◽  
Neda Soveyd ◽  
Mahmoud Djalali ◽  
Mansoureh Togha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
English Language ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Nuclear Factor Κb ◽  
General Term ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

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