Survey of Information Sources on Drug Safety In Patients Taking Non-Steroidal Anti-Inflammatory Drugs (original) (raw)
Related papers
Immuno-modulator metallo-Peptide reduces inflammatory state in obese zucker fa/fa rats
International journal of biomedical science : IJBS, 2014
Metabolic syndrome is a prothrombotic and proinflammatory chronic state. In obesity, the adipose tissue secretes various adipokines that take part in a variety of physiological and pathophysiological processes, including immunity and inflammation. Previous studies using a liver damage model treated with the immune-modulator metallo-peptide (IMMP) showed lessening in the degree of inflammation. Therefore, this study was set up to evaluate the anti-inflammatory effect of IMMP in obese Zucker fa/fa rats. We used Zucker-Lepr fa/fa and Zucker-Lean in this protocol. The groups received IMMP 50 ng/kg by i.p., three times per week for 8 weeks. Blood samples were collected by cardiac puncture and the serum was preserved at -80°C until analysis; the liver was excised and preserved in formaldehyde 4%. Analyses were performed to determine cytokine, insulin, glucose, triglyceride and cholesterol levels in serum, and histological analysis was also performed. IMMP treatment of obese rats resulted ...
Liver International, 2010
Background: Pro-inflammatory cytokines, such as tumour necrosis factor (TNF)-a, are known to be involved in the establishment of insulin resistance. Insulin resistance plays a key role in the development of obesity-related pathologies, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The state of chronic inflammation associated with obesity led us to hypothesize that TNF-a blockade may have an effect on experimentally obese animals. Aims: We studied the effects of thalidomide, an immunosuppressant and anti-TNF-a drug, on hepatic alterations that were induced by a high-fat diet (HFD) in mice. Methods: Obesity was induced in Swiss mice using a HFD for 12 weeks. Thalidomide-treated animals received thalidomide i.p. (100 mg/kg/day, 10 days). Glucose, aspartate aminotransferases and alanine aminotransferases levels were assessed in the blood. Insulin and glucose tolerance tests were performed. The liver was excised for histological, triglyceride, gene and protein expression analyses. Results: We found improvements in both the basal glucose blood levels and the response to insulin administration in the treated animals. The molecular analysis of insulin signalling revealed a restoration of the hepatic insulin receptor substrate (IRS)-1 and AKT phosphorylation. The hepatic expression of TNF-a was inhibited and the levels correlated with a significant reduction in the steatosis area. Other hepatic inflammatory markers, such as iNOS and suppressor of cytokine signalling (SOCS-3), were also reduced. Conclusions: We suggest that immunosuppressant drugs that target TNF-a and that may also contribute to reductions in the inflammatory markers that are associated with obesity could be a therapeutic option in NAFLD and type 2 diabetes.
International journal of molecular sciences, 2016
KMUP-1 (7-[2-[4-(2-chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9) and tumor necrosis factor α (TNFα), and related lipolysis via hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10) and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1-14 in high-fat diet (HFD)-supplemented C57BL/6J male mice (protection group) and from weeks 8-14, for 6 weeks, in HFD-induced obese mice (treatment group). Immunohistochemistry (IHC) and hematoxylin and eosin (H&E) staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on l...
International Journal of Diabetes in Developing Countries, 2016
Our study focused to assess the effect of various potential treatments on components of metabolic syndrome (MetS). This is a prospective, open-label, parallel group and randomized control trial of 90-day duration in which patients (n = 159) were randomly assigned in four groups to receive Bdiet and lifestyle modification^(n = 40), Bmetformin 500 mg twice daily^(n = 39), Bpioglitazone 15 mg once daily(n = 39), and Brosuvastatin 10 mg once daily^(n = 41). Clinical, biochemical, and inflammatory markers of each participant were evaluated. Fasting plasma glucose (FPG) level was lower in all except rosuvastatin group while HDLcholesterol level increased in rosuvastatin group only (p < 0.05). Serum triglyceride was significantly and comparably decreased in both pioglitazone and rosuvastatin group (p < 0.05). Significant decrease in hsCRP and increase in serum adiponectin (p < 0.05) were reported in all the groups from baseline. The study can add a step forward in devising standard pharmacotherapeutic regimen beyond the current treatment modalities.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-α, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
Anti-inflammatory Effect of Palmitoylethanolamide on Human Adipocytes
Obesity, 2009
Obesity leads to the appearance of an inflammatory process, which can be initiated even with a moderate weight gain. Palmitoylethanolamide (PEA) is an endogenous lipid, secreted by human adipocytes, that possesses numerous anti-inflammatory properties. The main purpose of this study was to investigate the anti-inflammatory effect of PEA on human adipocytes, as well as in a murine model. The production of tumor necrosis factor-α (TNF-α) by lipopolysaccharide (LPS)-treated human subcutaneous adipocytes in primary culture and CF-1 mice was investigated by enzyme-linked immunosorbent assay. The effects of PEA on adipocyte TNF-α secretion were explored as well as some suspected PEA anti-inflammatory pathways: nuclear factor-κB (NF-κB) pathway, peroxisome proliferatoractivated receptor-α (PPAR-α) gene expression, and TNF-α-converting enzyme (TACE) activity. The effects of PEA on the TNF-α serum concentration in intraperitoneally LPS-treated mice were also studied. We demonstrate that the LPS induced secretion of TNF-α by human adipocytes is inhibited by PEA. This action is neither linked to a reduction in TNF-α gene transcription nor to the inhibition of TACE activity. Moreover, PPAR-α is not implicated in this anti-inflammatory activity. Lastly, PEA exhibits a wide-reaching anti-inflammatory action as the molecule is able to completely inhibit the strong increase in TNF-α levels in the serum of mice treated with high doses of LPS. In view of its virtual lack of toxicity, PEA might become a potentially interesting candidate molecule in the prevention of obesity-associated insulin resistance.
Anti-TNF treatment does not reverse the abnormalities in lipid metabolism of the obese Zucker rat
American Journal of Physiology-Endocrinology and Metabolism, 1997
Because obesity, insulin resistance, and hyperlipidemia are often associated, and recent evidence suggests that the cytokine tumor necrosis factor-alpha (TNF) may influence the activity of insulin in various target tissues, the present study was designed to see whether TNF was also associated with the changes in lipid metabolism that lead to hyperlipidemia in the obese model of the Zucker rat. A polyclonal goat anti-rat TNF antibody was subcutaneously administered to Zucker rats for 4 days to block TNF actions. The results indicate that none of the alterations in lipid metabolism seen in the obese animals were reversed by the anti-TNF treatment. This was the case for the lipogenic rate in liver and adipose tissue, the disposal of an exogenous [14C]triolein load, adipose tissue lipoprotein lipase activity, and the hypertriglyceridemia. Measurements of lipolysis in adipose tissue slices from the anti-TNF-treated animals also did not show any significant effect of the treatment. In con...
SERUM BIOCHEMICAL AND INFLAMMATORY CYTOKINES IN A RAT MODEL OF METABOLIC SYNDROME
Yeldu and Mus'ab, 2020
Background: Metabolic syndrome (MetS) is a combination of cardio-metabolic risk factors including obesity, hyperglycaemia, dyslipidaemia, oxidative stress and hypertension. Aims and Objectives: This study was aimed at determining the serum concentrations of biochemical and inflammatory cytokines and assesses the correlation between the biochemical and inflammatory cytokines in a rat model of metabolic syndrome. Materials and Methods: Twenty rats were divided into 2 groups of 10 each: control (fructose untreated) and the fructose treated group. MetS was induced by oral administration of 10% fructose in water for 32 weeks. At the end of the experiment, rats were fasted for 12 hours and blood samples collected and body weight, body mass index (BMI), fasting blood glucose (FBG), serum lipid profile, interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α) were measured using standard techniques. Result: Result indicated significantly (P< 0.05) increased FBG, body weight, BMI, serum TC and LDL-C while, HDL-C levels significantly (P< 0.05) decreased in MetS group compared with controls. However, the levels of VLDL-C, TG and AIX were not significantly (P > 0.05) different between the groups. Significantly (P< 0.05) increased serum IL-6, IL-10 and TNF-α were observed in MetS group compared with controls. Serum IL-10 and TNF-α were inversely correlated with BMI. Serum IL-10 negatively correlated with FBG while, IL-6 was not correlated with either of BMI and FBG.Serum AIX and VLDL-C were positively correlated with TG while, HDL-C level was inversely correlated with TG. With the exception of serum LDL-C which positively correlated with TC, significant correlation was not established between serum TC and each of AIX, HDL-C and VLDL-C. Conclusion: The rat model of MetS was established after treatment with 10% fructose in water. This plays an important role in the pathogenesis of components of metabolic syndrome, including dyslipidaemia, hyperglycaemia and obesity; and serum IL-6, IL-10 and TNF-α are raised in metabolic syndrome and this underscores the role of these cytokines in inflammation associated with metabolic syndrome.
Anti-inflammatory agents as modulators of the inflammation in adipose tissue: A systematic review
PLOS ONE
Obesity is characterized by an adipose tissue mass expansion that presents a risk to health, associated with a chronic increase in circulating inflammatory mediators. Anti-inflammatory agents are an obesity alternative treatment. However, the lack of effective agents indicates the need to assess the mechanisms and identify effective therapeutic targets. The present work identified and described the mechanisms of action of anti-inflammatory agents in adipose tissue in experimental studies. The review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO—CRD42020182897). The articles’ selection was according to eligibility criteria (PICOS). The research was performed in PubMed, ScienceDirect, Scopus, Web of Science, VHL, and EMBASE. The methodological quality evaluation was assessed using SYRCLE. Initially, 1511 articles were selected, and at the end of the assessment, 41 were eligible. Among the anti-inflammatory agent classes, eight drugs, 28 natur...
2016
1Florin Casoinic, 1Dorel Sampelean, 2Anca D. Buzoianu, 3Nicolae Hancu, 4Dorina Baston 1 Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2 Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3 Department of Diabetology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4 Cardiovascular and Vascular Surgery Inpatient Unit, Toronto General Hospital, Toronto, Canada.