Pretreatment of curcumin attenuates coagulopathy and renal injury in LPS-induced endotoxemia
Department of Microbiology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. Journal of Endotoxin Research
(Impact Factor: 3.06).
02/2007; 13(1):15-23. DOI: 10.1177/0968051907078605
Disseminated intravascular coagulation (DIC) is a lethal situation in severe infections, characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. Current clinical trials are not promising. In this study, we investigated the protective effect of curcumin in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by sustained infusion of LPS (10 mg/kg body weight) for 4 h through the tail vein. Curcumin (60 mg/kg body weight) was given intraperitoneally 3 h before LPS infusion. Results showed that, in vivo, curcumin reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-alpha levels and the consumption of peripheral platelets and plasma fibrinogen. Furthermore, in vivo curcumin also has the effect of preventing the formation of fibrin deposition in the glomeruli of kidney. These results reveal the therapeutic potential of curcumin in infection-related coagulopathy of DIC.
Available from: Bharat Aggarwal
- "• Decreased the expression of TNF-a and reduced the mortality in rat model of sepsis (Siddiqui et al., 2006). • Reduced the mortality rate of LPS-infused rats by decreasing the circulating TNF-a levels and the consumption of peripheral platelets and plasma fibrinogen (Chen et al., 2007). • Significantly inhibited TNF-a and NO levels in rat model of diabetic neuropathy (Sharma et al., 2007b). "
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TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000-20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution.
This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8.
British Journal of Pharmacology 02/2013; 169(8). DOI:10.1111/bph.12131 · 4.84 Impact Factor
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ABSTRACT: Sepsis-related acute kidney injury (AKI) is an important complicating feature of sepsis, and is associated with greater complexity of care and higher mortality. Until recently, AKI lacked a standard, widely accepted definition, rendering it difficult to compare previously published strategies to prevent, recognize and treat this entity. Recently, the RIFLE classification of AKI has been developed, and confirmed in observational studies to be associated with subsequent morbidity and mortality. The management of sepsis-related AKI is evolving with new basic discoveries and ongoing translational clinical research, and will likely include nephroprotective strategies to protect kidneys in patients at risk, early recognition and amelioration of renal damage and pharmacological interventions to minimize injury and promote recovery. Furthermore, extracorporeal blood purification (EBP) has an important role to play, not only in the replacement of certain aspects of renal organ function such as acid-base/electrolyte homeostasis and extracellular fluid volume, but also in an immunomodulatory fashion. As a therapy that has the potential to influence the course of disease in sepsis, EBP in sepsis and sepsis-related AKI is the subject of this review.
Blood Purification 02/2008; 26(1):30-5. DOI:10.1159/000110560 · 1.28 Impact Factor
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ABSTRACT: Using primary rat mesencephalic neuron-glia cultures as an in vitro model of Parkinson's disease (PD), we tested the effect of curcumin, a natural dietary pigment with well-known anti-inflammation effects, on dopaminergic (DA) degeneration. Curcumin pretreatment mitigated LPS-induced DA neurotoxicity in a concentration-dependent manner and curcumin post-treatment also showed protective effect. Microglia depletion abolished this protective effect of curcumin, indicating that microglia play an important role in this effect. Supportively, observation by immunocytochemistry staining using OX-42 antibody showed that curcumin treatment inhibited LPS-induced morphological change of microglia. Besides, LPS-induced production of many proinflammatory factors and their gene expressions decreased dramatically after curcumin treatment. Results also revealed that curcumin treatment decreased LPS-induced activation of two transcription factors--nuclear factors kappaB (NF-kappaB) and activator protein-1 (AP-1). Taken together, our study implicated that curcumin might be a potential preventive and therapeutic strategy for inflammation-related neurodegenerative diseases.
Neurochemical Research 04/2008; 33(10):2044-53. DOI:10.1007/s11064-008-9675-z · 2.59 Impact Factor
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