curcumin and Liver-Failure--Acute

Acute liver injury (ALI) is a severe syndrome and can further develop into acute liver failure (ALF) which can lead to high mortality and cause irreversible liver injuries in the clinic. Liver transplantation is the most common treatment; however, liver donors are lacking, and the progression of ALF is rapid. Nanoparticles can increase the bioavailability and the targeted accumulation of drugs in the liver, so as to significantly improve the therapeutic effect of ALI. Curcumin derivative COP-22 exhibits low cytotoxicity and effective anti-inflammatory activity; however, it has poor water solubility. In this study, COP-22-loaded bovine serum albumin (BSA) nanoparticles (22 NPs) were prepared and characterized. They exhibit effective hepatoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis on Lipopolysaccharide/D-Galactosamine-induced acute liver injury of mice. The anti-inflammatory activity of 22 NPs is related to the regulation of the NF-κB signaling pathways; the antioxidant activity is related to the regulation of the Nrf2 signaling pathways; and the apoptosis activity is related to mitochondrial pathways, involving Bcl-2 family and Caspase-3 protein. These three cellular pathways are interrelated and affected each other. Moreover, 22 NPs could be passively targeted to accumulate in the liver through the retention effect and are more easily absorbed than 22.HCl salt in the liver.

Topics: Albumins; Animals; Anti-Inflammatory Agents; Chemical and Drug Induced Liver Injury; Curcumin; Galactosamine; Lipopolysaccharides; Liver; Liver Failure, Acute; Mice; Nanoparticles; NF-kappa B

Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties.. To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R.. Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1β, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation.. We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Curcumin; Dimethyl Fumarate; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Heme Oxygenase (Decyclizing); Humans; Immunosuppressive Agents; Liver Failure, Acute; Male; NF-E2-Related Factor 2; Rats; Reperfusion Injury; Signal Transduction

Curcumin is a major active phenolic component of turmeric and has gained great attention in pharmaceutics due to its potent antioxidant, anti-inflammatory and anticancer activity. Here, we developed poly(oxalate-co-curcumin) (POC) as a hydrogen peroxide (H

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Curcumin; Hydrogen Peroxide; Liver Failure, Acute; Male; Mice; Mice, Inbred ICR; Polymers; Prodrugs; RAW 264.7 Cells; Ultrasonography

Acute paracetamol (PCM) toxicity is a clinical problem; can result in a serious liver injury that finally may progress to acute liver failure. Curcumin (CUR) is a prevalent natural compound that can maintain prooxidant/antioxidant balance and thus can help in liver protection; also, Silymarin (SL) is a traditional antioxidant herb, used to treat liver disorders through scavenging free radicals. This study aimed to illustrate the histological, biochemical and molecular changes induced by acute PCM overdose on rats' liver to elucidate the effectiveness of CUR compared to SL in alleviating such changes.. Male Wister Albino rats were divided into 6 groups each comprising 23 rats: control group, curcumin (CUR) treated group received (100 mg CUR/ kg), silymarin treated group received (100 mg SL/kg) for 7 successive days. Paracetamol (PCM) exposed group administered a single dose of PCM (200 mg/kg orally on 8th day). PCM + CUR group and PCM + SL group pretreated with CUR and SL respectively for 7 days then received single PCM dose (200 mg/kg) on the 8th day. Blood and liver tissues were collected for biochemical, histopathological and immunohistochemical analyses using anti-p53 antibody. In addition, real time polymerase chain reaction (RT- PCR) was used to measure Bax, bcl2 and Peroxisome proliferator-activated receptor-gamma (PPAR γ) mRNA expression levels.. In the paracetamol overdose group, the liver architecture showed necrotic changes, hydropic degeneration, congestion and dilatation of central veins. This hepatocellular damage was confirmed by a significant increase of AST, ALT levels and by an apparent increase in the number of p53 stained cells. PCM toxicity showed significant elevation of total oxidant status (TOS), oxidant status index (OSI) and decreased total antioxidant capacity (TAC) compared to controls (p < 0.001). Gene expression analysis showed that PCM caused an elevation of bcl2 and a reduction of both Bax and PPARγ mRNA expression. The histological alternation in the liver architecture was markedly improved in (PCM + CUR) group compared to (PCM+ SL) group, with an obvious decrease in the number of P53 stained cells. CUR pretreatment inhibited the elevation of TOS and OSI as well as the reduction of TAC caused by PCM toxicity compared to (PCM + SL) group.. Both SL and CUR pretreatment prevented the toxic effects of PCM, but CUR is more effective than SL in ameliorating acute PCM induced hepatotoxicity.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Curcumin; Drug Synergism; Immunohistochemistry; Liver; Liver Failure, Acute; Male; Oxidants; Oxidative Stress; Plant Extracts; PPAR gamma; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Silymarin

Curcumin is a phenolic product isolated from the rhizome of Curcuma longa and has protective effects on inflammatory diseases. Here we investigated the protective effect of curcumin in acute Propionibacterium acnes (P. acnes)-induced inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by LPS challenge to induce fulminant hepatitis. Curcumin or vehicle control was administered perorally by gavage once daily starting 2days before P. acnes priming. We found that curcumin significantly improved mouse mortality. Then, to investigate the underlying mechanisms of curcumin in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We found that curcumin treatment attenuated P. acnes-induced liver injury as evidenced by decreased production of ALT. In addition, curcumin treatment reduced the production of proinflammatory cytokines such as TNF-α and IFN-γ, accompanied by reduced hepatocyte apoptosis. Furthermore, curcumin treatment significantly reduced HMGB1 cytoplasmic translocation and expression by down-regulating acetylation of lysine. Taken together, our results suggest that curcumin protects mice from P. acnes-induced liver injury through reduction of HMGB1 cytoplasmic translocation and expression.

Topics: Acetylation; Acute Disease; Animals; Apoptosis; Curcuma; Curcumin; Gram-Positive Bacterial Infections; Hepatocytes; HMGB1 Protein; Interferon-gamma; Liver; Liver Failure, Acute; Mice; Mice, Inbred C57BL; Propionibacterium acnes; Protein Transport; Rhizome; Tumor Necrosis Factor-alpha

Curcumin possesses anti-inflammatory and antioxidant effects. Curcumin pretreatment provided a hepatoprotective effect in rat models of chemically-induced hepatotoxicities and ischemia/reperfusion injuries. In this study, we examined whether curcumin could improve the survival rate of rats undergoing a 90% hepatectomy.. Rats were administered 340 mg/kg oral curcumin formulated with phosphatidylcholine (curcumin group) or vehicle (control group) for 7 consecutive days and 2 hours prior to the massive hepatectomy.. Six of the 13 rats pretreated with curcumin survived, whereas all 13 rats pretreated with vehicle died within day 2 following a massive hepatectomy. A histological examination showed the lobular structure to be disturbed in the rats pretreated with vehicle, whereas the hepatic lobular structure remained relatively stable without necrosis in the rats pretreated with curcumin. The contents of heme oxygenase-1 (HO-1) protein in the control group were low in the preoperative phase. In contrast, the levels of HO-1 protein in the curcumin group were high at the preoperative phase, and thereafter remained at high levels until day 7 following surgery.. Our results suggest that curcumin improves the survival rate by increasing the antioxidant activity in rats after a massive hepatectomy.

Topics: Animals; Antioxidants; Bilirubin; Blotting, Western; Curcumin; Cytoprotection; Heme Oxygenase (Decyclizing); Hepatectomy; Immunohistochemistry; Interleukin-6; Liver; Liver Failure, Acute; Liver Regeneration; Male; Malondialdehyde; Necrosis; Rats; Rats, Inbred F344; Time Factors

Increased production of reactive oxygen species and nitric oxide and activation of nuclear factor kappa B are implicated in the pathogenesis of various liver diseases, including fulminant hepatic failure. Curcumin is a naturally occurring anti-oxidant that reduces oxidative stress and inhibits nuclear factor kappa B and nitric oxide formation. The aim of the present study is to assess curcumin's therapeutic potential in acute thioacetamide hepatotoxicity, a rat model of fulminant hepatic failure.. Fulminant hepatic failure was induced by two intraperitoneal (i.p.) injections of 300 mg/kg thioacetamide (TAA) at 24-h intervals. The experimental groups received a low-dose (200 mg/kg per day, i.p.) or a high-dose (400 mg/kg per day) of curcumin, initiated 48 h prior to the first TAA injection. A fourth group was administered neither TAA nor curcumin and served as a control.. The survival rate was higher in both curcumin-treated groups compared to the TAA only treated group. Biochemical parameters of liver injury, blood ammonia and hepatic necroinflammation were lower in the low-dose curcumin group compared to TAA controls, and were further reduced in the high-dose group (P < 0.05 and P < 0.01, respectively). Curcumin treatment also reduced the TAA-induced elevated hepatic levels of thiobarbituric acid-reactive substances (TBARS), and inhibited the nuclear binding of nuclear factor kappa B (NFkappaB) and inducible nitric oxide (iNOS) protein expression.. Curcumin improved survival and minimized oxidative stress, hepatocellular injury and hepatic necroinflammation, NFkappaB binding and iNOS expression in a rat model of FHF. These findings support the role of ROS, NFkappaB and iNOS in mediating liver insult due to TAA, and that of curcumin as a hepato-protectant.

Topics: Animals; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Liver Failure, Acute; Male; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Thioacetamide; Thiobarbituric Acid Reactive Substances; Treatment Outcome