Aquaporin and Blood Brain Barrier

Large water fluxes continuously take place between the different compartments of the brain as well as between the brain parenchyma and the blood or cerebrospinal fluid

NF-κB — A Key Factor in Atherogenesis and Atheroprogression

Atherosclerosis is the major cause of cardiovascular diseases and it is responsible for a large proportion of mortality in the Western society

NLRP3 inflammasome modulation by melatonin supplementation in chronic pristane-induced lupus nephritis

Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). NLRP3 inflammasome activation is implicated in LN pathogenesis, suggesting its potential targets for LN treatment. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule that has been reported to have anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-κB)-mediated inflammatory responses in vivo. This molecule has also protective effects against the activation of the inflammasomes and, in particular, the NLRP3 inflammasome. Thus, this work evaluated the effect of melatonin on morphological alteration and NLRP3 inflammasome activation in LN pristane mouse models. To evaluate the melatonin effects in these mice, we studied the renal cytoarchitecture by means of morphological analyses and immunohistochemical expression of specific markers related to oxidative stress, inflammation and inflammasome activation. Our results showed that melatonin attenuates pristane-induced LN through restoring of morphology and attenuation of oxidative stress and inflammation through a pathway that inhibited activation of NLRP3 inflammasome signaling. Our data clearly demonstrate that melatonin has protective activity on lupus nephritis in these mice that is highly associated with its effect on enhancing the Nrf2 antioxidant signaling pathway and decreasing renal NLRP3 inflammasome activation

Browning of Adipose Tissue and Sirtuin Involvement

Obesity is an important risk factor for many diseases, including cardiovascular diseases, metabolic syndrome and cancers. Excessive dietary intake of caloric food results in its accumulation in white adipose tissue (WAT), whereas energy expenditure by fat utilization and oxidation predominately occurs in brown adipose tissue (BAT). Reducing obesity has become an important prevention strategy of research interest, focusing in the recent years, mainly on browning of WAT, the process during which the enhance of the mitochondria biogenesis occurs and then white adipocytes are converted to metabolically active beige adipocytes. Sirtuin1 (SIRT1), the most known isoform of sirtuin deacetylases, is implied in the browning of WAT process. In fact, it is a sensitive sensor of cell energy metabolism and, together with other sirtuin isoforms, contributes to this differentiation process. This chapter provides an overview about SIRT1 involvement in browning of WAT as a target molecule that can thereby contrast obesity

Endoplasmic Reticulum Involvement in Heart Injury: An Overview

The Endoplasmic Reticulum (ER) is a multifunctional organelle present in the cytoplasm of the eukaryotic cells. It is involved in many aspects of cellular physiology and it presents important interaction with other cellular organelles. Different physiological and/or pathological factors may alter ER morphology and homeostasis, resulting in the accumulation of a large number of unfolded/misfolded proteins in the ER lumen and so inducing ER stress. Alterations in ER have been found to be related to different disorders. In particular, ER stress is implicated in the development and progression of various heart injuries, such as myocardial infarction, ischemia/reperfusion, heart failure, diabetic cardiomyopathy, arrhythmias and cardiotoxicity. Furthermore, the efficiency to counteract the ER stress declines significantly during the physiopathological aging process. In this chapter, we present the correlation between the ER and cardiac injury focusing mainly on the aging process and then we report a brief overview of the potential involvement of some bioactive molecules as preventive/therapeutic compounds that can contrast heart disorders through ER modulation

Potential protective effects of melatonin against UV-A irradiation on fibroblast cell line

The sun’s radiation that reaches Earth contains ultraviolet (UV) wavelights made up of a combination of UV-A (95%) and UV-B (5%) radiations. Chronic sun exposure is responsible for long term clinical skin changes such as photoaging, photodamage and photocancers. Moreover, inflammation is mostly due to UV-A which stimulates the production of reactive oxygen species (ROS) inducing also photoaging (Mouchet et al., 2010; Marionnet et al., 2010). In order to protect themselves against oxidative stress, skin cells developed several defense systems, including ROS and metal ions scavengers and a battery of detoxifying and repair enzymes (Bickers and Athar, 2006). In addition, UV-A can also directly influence the structure of nucleic acids, breaking the chain or changing the nucleotide sequence. Altogether these perturbations of cells homeostasis advantages a significant up-regulation of oxidative and inflammatory responsive genes. In this study, we focused our attention on prevention of photodamage, choosing melatonin as antioxidant agent. Melatonin is a neuroendocrine mediator with pleiotropic bioactivities such as hormonal, neurotransmitter, immunomodulator and biological modifier actions. Its antioxidant activity is the result of two different but synergic actions: a direct, due to its ability to act as a free radical scavenger and an indirect due to the up-regulation of antioxidant enzymes (Fischer et al., 2008). The aim of the present study was to analyze the impact of pre-treatment of murine fibroblasts cells (NIH-3T3) with melatonin (10-3 M- kindly provided by Chronolife S.r.l., Roma, Italy) later irradiated by UV-A irradiation (15 J/ cm2) evaluating the changes of fibroblast microenvironment conditions. We observed that UV-A irradiation caused matrix restructuration and alteration, oxidative stress and inflammation; while melatonin pre-treatment suppresses UV-A induced photodamage. Collectively, these results suggest that melatonin provides relevant protective effects against UV-A irradiation. A new chapter of melatonin in dermato-endocrine research could be open

Promising Antineoplastic Actions of Melatonin

Melatonin is an endogenous indoleamine with an incredible variety of properties and activities. In recent years, an increasing number of studies have investigated this indoleamine’s interaction with cancerous cells. In particular, it seems that melatonin not only has the ability to improve the efficacy of many drugs used in chemotherapy but also has a direct inhibitory action on neoplastic cells. Many publications underlined the ability of melatonin to suppress the proliferation of various cancer cells or to modulate the expression of membrane receptors on these cells, thereby reducing tumor aggressiveness to metastasize. In addition, while melatonin has antiapoptotic actions in normal cells, in many cancer cells it has proapoptotic effects; these dichotomous actions have gained the interest of researchers. The increasing focus on melatonin in the field of oncology and the growing number of studies on this topic require a deep understanding of what we already know about the antineoplastic actions of melatonin. This information would be of value for potential use of melatonin against neoplastic diseases

Role of Apolipoproten E in liver aging protection

Aging is characterized by a progressive decline of cellular functions. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver. Endogenous free radicals are generated within mitochondria and suspected to cause severe injury to mitochondrial DNA. This damaged DNA accumulates with aging. In addition, polyunsaturated fatty acids, highly sensitive to ROS, decrease in liver mitochondria from human centenarians, a feature acquired during evolution as a protective mechanism to favor longevity. Diet is considered the main environmental factor having effect on lifespan. It has a major impact on aging liver, the central metabolic organ of the body. Apolipoprotein E (apoE) null mice are a very popular model for studying spontaneous hypercholesterolemia, but only limited data are available for the role of apolipoprotein E in liver disease. The purpose of this study is to evaluate liver disease in apolipoprotein E deficient mice. For this study, apoE null mice and control mice at different ages (6 weeks and 15 months) were used. Liver morphological damage and proteins involved in oxidative stress, apoptosis and aging (Bax, Sirt 1, p53) were analyzed. ApoE deficient mice have morphological alterations that are the hallmark of liver pathogenesis, which increase with the age of the animals. In apoE null mice livers, there is also increased oxidative stress as compared to control mice at the same age and fewer antioxidant enzymes. Our findings add to the growing list of protective effects that apoE possesses

NPP1 inhibits intimal hyperplasia in ApoE knockout mice

Atherosclerosis is an important cause of morbidity and mortality, which is increasingly recognized and reported on a global scale. This pathology is due to multiple metabolic toxicity including increased levels of reactive oxygen species (ROS). Excessive ROS are damaging to proteins, lipids, carbohydrates and nucleic acids, which prompt a classic “response to injury” mechanism including inflammation supporting a cytokine surge, granulation and fibrosis. ROS are excessive, robustly produced in atherosclerosis associated with endothelial dysfunction. Excessive ROS due to osteopontin (OPN) increase may be the driving force promoting atherosclerotic process. Recently has been shown that ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) promotes atherosclerosis, potentially mediated by OPN expression in ApoE knockout mice (Nitschke et al., 2011). Hence, this study tested the hypothesis that NPP1 deficiency modulates intimal hyperplasia and oxidative stress in the atherosclerotic process. For this study were used ApoE null mice and Npp1/ApoE double deficient mice. Atherosclerotic lesion area, calcification and vascular alterations were examined at 13, 18, 23 and 28 weeks of age. Morphological changes in vessels were evaluated by histological procedures and immunohistochemical analysis using thrombospondin-1 (TSP-1), transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor-1 (PAI-1) and oxidative stress markers such as superoxidodismutase (SOD) and inducible nitric oxide synthase (iNOS). In ApoE null mice vessels we demonstrated vascular alterations with extensive accumulation of collagen and elastic fibers and also an increase of TSP-1, TGF-β1, PAI-1 expression and oxidative stress related protein levels compared to Npp1/ApoE double deficient mice. Moreover, histological analysis showed neointima formation only in ApoE deficient mice. Our findings suggest that NPP1 could be involved in intimal hyperplasia and oxidative stress in the atherosclerosis pathway