Abstract：
:Acute lung injury (ALI) and acute kidney injury (AKI) are major causes of sepsis-induced mortality. The objective of the study is to evaluate the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, in sepsis-induced ALI and AKI using the cecal ligation and puncture (CLP) rat model of sepsis. Clinical and experimental studies have demonstrated the importance of IL-6 in sepsis; however, the role of TCZ has not been investigated. Rats subjected to CLP developed histological evidence of ALI and AKI at 24 h. We found that TCZ alleviated sepsis-induced ALI and AKI as evidenced by improvements in various pathological changes, a significant reduction in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid (BALF), and a significant decrease in the elevated serum level of creatinine (CR) and blood urea nitrogen (BUN). TCZ induced an increase in the survival rate of treated rats. Additionally, TCZ markedly inhibited sepsis-induced pulmonary and renal inflammatory responses. Moreover, we found that treatment with TCZ inhibited oxidative stress and apoptosis in lung and kidney tissue. TCZ treatment significantly inhibited NF-κB activation, attenuating JNK signaling pathway and significantly up-regulated P-glycoprotein (P-gp) expression in pulmonary as well as in renal tissues. Our data provide novel evidence that TCZ has a protective effect against sepsis-induced ALI and AKI by blocking IL-6 receptor signaling. This could provide a molecular basis for a new medical treatment for sepsis-induced ALI and AKI.
journal_name
Inflammopharmacologyjournal_title
Inflammopharmacologyauthors
Ibrahim YF,Moussa RA,Bayoumi AMA,Ahmed AFdoi
10.1007/s10787-019-00628-ysubject
Has Abstractpub_date
2020-02-01 00:00:00pages
215-230issue
1eissn
0925-4692issn
1568-5608pii
10.1007/s10787-019-00628-yjournal_volume
28pub_type
杂志文章abstract：:Most of the gastroprotective drugs which had been marketed in Japan were considered to have insufficient rationale for use as ulcer treatments. Such drugs may have a crucial role in maintaining mucosal integrity by the mechanisms other than inhibition of acid secretion. We re-evaluated the effect of gastroprotective d...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-006-0300-y
更新日期：2007-02-01 00:00:00
abstract：:Pain is recognized as a multifactorial sensory experience that is wholly unpleasant. It can vary in intensity from mild to severe and its duration can be anything from transient to persistent. Today we know so much more about the peripheral nociceptor as the primary detection apparatus for painful stimuli. We also und...
journal_title：Inflammopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s10787-009-0006-z
更新日期：2009-06-01 00:00:00
abstract：:The up-regulation of angiotensin II AT1 receptors has been implicated as a major mediator in the development of hypertension and progressive nephropathy in experimental diabetes. In spite of the documented potential of garlic treatments in ameliorating diabetic complications, the possible involvement of the angiotensi...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-012-0139-3
更新日期：2013-04-01 00:00:00
abstract：:The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier regulating its homeostasis. Blood-brain barrier is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted num...
journal_title：Inflammopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s10787-018-0468-y
更新日期：2018-06-01 00:00:00
abstract：AIMS:To compare methodological aspects of the impact of different classification procedures used in three phases of a twin study examining genetic factors in the aetiopathogenesis of rheumatoid arthritis (RA). METHODS:We have previously reported the results of a study of the aetiopathogenesis of RA based on the Austra...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-998-0009-1
更新日期：1998-01-01 00:00:00
abstract：:Excess eicosanoid formation during inflammation has been attributed to the expression of the gene coding for the inducible isoform of prostaglandin G/H synthase (PGHS-2). Human and murine PGHS-2 proteins differ in 73 out of the 604 amino acids. When comparing the inhibitory effects of a panel of PGHS-inhibitors in a w...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-997-0020-y
更新日期：1997-01-01 00:00:00
abstract：:Stress is a reflex response, both psychological and physiological, of the body to a difficult situation that requires adaptation. Stress is at the intersection of the objective event and the subjective event. The physiological mechanisms involved in chronic stress are numerous and can contribute to a wide variety of d...
journal_title：Inflammopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s10787-018-0546-1
更新日期：2019-02-01 00:00:00
abstract：BACKGROUND:Hydroxychloroquine (HCQ) is a widely prescribed medication to patients with systemic lupus erythematosus (SLE), with potential anti-inflammatory effects. This study was performed to investigate the efficacy of HCQ therapy by serial assessment of disease activity and serum levels of proinflammatory cytokines ...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-018-0512-y
更新日期：2018-10-01 00:00:00
abstract：:The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogeno...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-009-0009-9
更新日期：2009-08-01 00:00:00
abstract：:The initial precipitating injury such as SE progresses to chronic epilepsy through multiple epileptogenic processes. Early epileptogenic events are generally characterized by neuroinflammation, neurodegeneration and abnormal neurogenesis in the hippocampus. Metformin has exhibited anti-inflammatory and neuroprotective...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-020-00782-8
更新日期：2021-01-01 00:00:00
abstract：INTRODUCTION:Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγT) is a lineage specifying transcription factor for IL-17 expressing cells, which may contribute to the pathogenesis of Inflammatory Bowel Disease (IBD). VPR-254 is a selective in vitro inhibitor of RORγT. AIMS:The main goals of our study were two...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-019-00643-z
更新日期：2020-04-01 00:00:00
abstract：OBJECTIVE:This pilot study aimed to determine the efficacy of acamprosate (N-acetyl homotaurine) in reducing the pathological features of experimental autoimmune encephalomyelitis (EAE) which is an animal model for multiple sclerosis (MS). BACKGROUND:The amino acid taurine has multiple biological activities including ...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-011-0097-1
更新日期：2012-02-01 00:00:00
abstract：:2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) with COX-2 enzyme inhibition, analgesic, anti-inflammatory and antipyretic potentials were executed and reported. From the in vitro COX-2 enzyme inhibition assay, compounds 4 h (IC50 0.026 µM) and 4j (IC50 0.102 µM) were found as most potent COX-2 inhibitors. Consequ...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-017-0342-3
更新日期：2017-12-01 00:00:00
abstract：:Rhynchosia minima root, a folk herbal medicine in southern China, is used to relieve itch and swelling. In this study, we examined the anti-inflammatory property of an ethanol fraction (EEF6) from R. minima root on lipopolysaccharide (LPS)-induced RAW 264.7 cells, as well as its underlying mechanism. The compound comp...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-019-00632-2
更新日期：2020-02-01 00:00:00
abstract：:Genistein is an isoflavone with oestrogenic activity that is present in a variety of soy products as a constituent of complex mixtures of bioactive compounds, whose matrix profiles play an important role in determining the overall oestrogenic bioactivity of genistein. We review data on how the profile of soy bioactive...
journal_title：Inflammopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s10787-008-8020-0
更新日期：2008-10-01 00:00:00
abstract：:We clarified the roles of histamine H(1)-, H(2)-, H(3)-receptors and oxyradicals in the exacerbation of acid-induced gastric haemorrhage and stomach ulcer in endotoxaemic rats by measuring changes in gastric mucosal glutathione concentrations, lipid peroxide generation and histamine levels as well as in luminal electr...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-998-0017-1
更新日期：1998-01-01 00:00:00
abstract：:Tovophyllin A (TA) is a xanthone isolated from Garcinia mangostana L. (GM, Guttiferae) pericarps that possesses various beneficial bioactivities. However, its protective effects on acute lung injury (ALI) and lung carcinoma have not yet been explored. The current work was designed to investigate the protective potenti...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-019-00609-1
更新日期：2020-02-01 00:00:00
abstract：:Allanblackia gabonensis (Guttiferae) is a plant used in the African traditional medicine as remedies against pain, rheumatism, inflammations. In the present work, the analgesic effect of aqueous extract has been evaluated using acetic acid, formalin, hot-plate test, tail immersion and paw-pressure test. The anti-infla...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-011-0096-2
更新日期：2013-02-01 00:00:00
abstract：:The inflamed mucosa in ulcerative colitis produces high amount of prostaglandin (PG) and nitric oxide (NO) through inducible enzymes: cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, implicating them as potential anti-inflammatory drug targets. COX-2 or iNOS-related treatments in diff...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-007-1603-3
更新日期：2007-10-01 00:00:00
abstract：:P38 mitogen-activated protein kinase (p38 MAPK), a tissue inflammatory factor can be activated under oxidative stress and in conditions associated with hyperglycemia. Gingerol containing various natural herbs has been extensively studied for its pharmacological actions both in reducing the inflammation and as immunity...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-019-00569-6
更新日期：2019-12-01 00:00:00
abstract：:The ulcerogenic effect of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the gastrointestinal mucosa was investigated in the presence of a low dose of indomethacin. Indomethacin at 3 mg/kg did not cause any damage in both the stomach and small intestine, despite inhibiting prostaglandin (PG) production....
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1163/156856005774423755
更新日期：2005-01-01 00:00:00
abstract：BACKGROUND:There is considerable interest in the possible importance of the gut microflora in the pathophysiology of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD). Probiotics offer a potential adjuvant treatment in these patients by modifying the intestinal milieu, but reports o...
journal_title：Inflammopharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10787-019-00595-4
更新日期：2019-06-01 00:00:00
abstract：:Prompted by the findings that smokers have lowered brain and blood platelet monoamine oxidase-A and -B activities compared to non-smokers and that smokers have a lowered incidence of Parkinson's disease, we have examined the neuroprotective properties of an MAO inhibitor, 2,3,6-trimethyl-1,4-naphthoquinone (TMN), whic...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1163/156856003765764353
更新日期：2003-01-01 00:00:00
abstract：BACKGROUND:Osthole is a bioactive component reported in medicinal plants such as Angelica pubescens and Cnidium monnieri, known for analgesic activity. However, the toxicity, median effective dose (ED50), and dual modulation of nitric oxide and cyclooxygenase pathways along with inflammatory cytokines of osthole are ye...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-018-0486-9
更新日期：2019-10-01 00:00:00
abstract：:Propolis has been extensively used to improve health and prevent inflammatory diseases. Different types of Cuban propolis (red, brown and yellow) have been documented. The purpose of this research was to investigate the cytotoxic effects of Cuban red propolis (CP) on MDA MB-231 cell line, since breast cancer is consid...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-018-0492-y
更新日期：2019-10-01 00:00:00
abstract：:Inflammatory bowel diseases are associated with reduced colonic contractility and induction of cyclooxygenase-2. In this study a possible role of cyclooxygenase-2 in and the underlying mechanism of the reduced contractility were investigated in experimental colitis. The effects of meloxicam, a cyclooxygenase-2 selecti...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-006-1507-7
更新日期：2006-03-01 00:00:00
abstract：:The safety of the cyclo-oxygenase-2 (COX-2) selective NSAID, nimesulide, has been evaluated from information (a) in clinical trials in osteoarthritis that have been performed in Europe as well as in earlier pilot studies that were performed in patients with rheumatoid arthritis in the USA, and (b) in post-marketing st...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-998-0020-6
更新日期：1998-01-01 00:00:00
abstract：:Some B vitamins exhibit activities in models of nociceptive pain, inflammatory pain, and neuropathic pain induced by nerve lesions and also in certain painful conditions in humans. In the present study, we investigated the effects of thiamine, riboflavin, and nicotinamide in a neuropathic pain model induced by the che...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1007/s10787-019-00625-1
更新日期：2020-02-01 00:00:00
abstract：:There is a growing body of evidence that plant polyphenols such as resveratrol, anthocyanins, catechins, and terpenes like taxol are effectively used in the treatment of chronic conditions including cancer, Alzheimer, Parkinsonism, diabetes, aging, etc. The link between oxidative stress and inflammation is well accept...
journal_title：Inflammopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s10787-015-0236-1
更新日期：2015-08-01 00:00:00
abstract：:- The use of the non-steroidal anti-inflammatory drug, diclofenac, is associated with occasional serious side effects in the gastrointestinal (GI) tract. We examined the effect of altering the site of release of diclofenac sodium on GI tract side effects. Dissolution and pharmacokinetic studies were carried out to sub...
journal_title：Inflammopharmacology
pub_type： 杂志文章
doi：10.1163/156856004773121383
更新日期：2004-01-01 00:00:00
