The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury.

@article{Getachew2016TheST,
  title={The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an Experimental Model of Chronic Liver Injury.},
  author={Yonas Getachew and Frank A Cusimano and P. Gopal and S. Reisman and J. Shay},
  journal={Toxicological sciences : an official journal of the Society of Toxicology},
  year={2016},
  volume={149 1},
  pages={
          111-20
        }
}
UNLABELLED Patients with cirrhosis have an increased risk of developing liver cancer and a higher rate of mortality. Cirrhosis currently has no known cure, and patients may benefit from new agents aimed at alleviating their complications and slowing down the rate of disease progression. Therefore, the effects of the orally bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28-oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and antiinflammatory… Expand
CDDO and Its Role in Chronic Diseases.
TLDR
Positive results have been obtained in the laboratory and clinical trials with CDDO derivatives treating conditions such as lung injury, inflammation and chronic kidney disease, however, clinical trials for cancer and cardiovascular disease have not shown equally positive results and further exploration of CDDO and its derivatives is needed. Expand
Synthetic oleanane triterpenoids enhance blood brain barrier integrity and improve survival in experimental cerebral malaria
TLDR
It is indicated that SO are a new class of immunomodulatory drugs and support further studies investigating this class of agents as potential adjunctive therapy for severe malaria. Expand
Oleanolic Acid-amino Acids Derivatives: Design, Synthesis, and Hepatoprotective Evaluation In Vitro and In Vivo
TLDR
It is found that OA-lysine derivative (3g) could improve the hydrophilic of OA and induce HSCs apoptosis via inducing MMP depolarization and increasing intracellular Ca2+ levels and has the potential to be developed as an agent with hepatoprotective activity. Expand
Omaveloxolone and TX63682 are hepatoprotective in the STAM mouse model of nonalcoholic steatohepatitis
TLDR
Omaveloxolone and related Nrf2 activators may be useful for the treatment of NASH and results were associated with significant induction of NRF2 target gene expression in the liver, including NAD(P)H:quinone oxidoreductase 1, sulfiredoxin 1, and ferritin heavy chain 1. Expand
NOX2-ROS-HIF-1α signaling is critical for the inhibitory effect of oleanolic acid on rectal cancer cell proliferation.
TLDR
Novel insights are provided into OA-induced inhibition of rectal cancer cell proliferation and NOX2/ROS/HIF-1α axis is highlighted as a novel therapeutic target for the treatment ofrectal cancer. Expand
Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD
TLDR
The data suggest that the increases in ALT and AST observed clinically were, at least in part, related to the pharmacological induction of aminotransferases via Nrf2 activation, rather than to any intrinsic form of hepatotoxicity. Expand
Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses
TLDR
It is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity. Expand
Antioxidant and Antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl4-Induced Acute Liver Injury in Mice
TLDR
GTP achieves hepatoprotective effects by improving hepatic antioxidant status and preventing cell apoptosis through caspase-3-dependent signaling pathways by eliminating free radicals and improving superoxide dismutase, catalase, and glutathione peroxidase activity in the liver. Expand
Oleanane-, ursane-, and quinone methide friedelane-type triterpenoid derivatives: Recent advances in cancer treatment.
TLDR
A number of semisynthetic derivatives of oleanane-, ursane- and quinone methide friedelane-type PTs with anticancer activity have been synthetized aiming to improve their therapeutic activity and pharmacokinetic properties, and decrease their toxicity. Expand
Protective effects of Foeniculum vulgare root bark extract against carbon tetrachloride-induced hepatic fibrosis in mice
TLDR
It is indicated that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice. Expand
...
1
2
...

References

SHOWING 1-10 OF 46 REFERENCES
The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice.
TLDR
The number, size, and severity of lung carcinomas were markedly reduced and suppression of phosphorylation of the transcription factor signal transducers and activators of transcription 3 as well as induction of apoptosis in human lung cancer cell lines. Expand
Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor
TLDR
Species-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease and CCl4-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC. Expand
Synthetic Triterpenoids Prolong Survival in a Transgenic Mouse Model of Pancreatic Cancer
TLDR
It is suggested that oleanane triterpenoids and rexinoids have the potential to prevent pancreatic cancer. Expand
c-FLIP downregulation contributes to apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) in human lung cancer cells
TLDR
The modulatory effects of CDDO-Me on the levels of c-FLIP, a major inhibitor of death receptor-mediated caspase-8 activation, and its impact on CD DOE-Me-induced apoptosis and enhancement of TRAIL-induced suicides in human lung cancer cells are determined. Expand
Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells through a ROS-dependent mechanism.
TLDR
It is shown that CDDO-Me induces ROS generation from both nonmitochondrial and mitochondrial sources, which is associated with the induction of apoptosis as characterized by increased annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c. Expand
Synthetic triterpenoids inhibit growth, induce apoptosis and suppress pro-survival Akt, mTOR and NF-{kappa}B signaling proteins in colorectal cancer cells.
TLDR
Testing the apoptosis-inducing activity of oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid and its C-28 methyl ester and C- 28 imidazole derivatives in colorectal cancer cells lines provides rationale for clinical evaluation of CDDO-Me for the treatment of advanced chemotherapy refractory coloreCTal cancer. Expand
CDDO-Im protects from acetaminophen hepatotoxicity through induction of Nrf2-dependent genes.
TLDR
It is shown that CDDO-Im pretreatment induces Nrf2-dependent cytoprotective genes and protects the liver from acetaminophen-induced hepatic injury. Expand
New Synthetic Triterpenoids: Potent Agents for Prevention and Treatment of Tissue Injury Caused by Inflammatory and Oxidative Stress
TLDR
The original rationale for the development and the chemistry of a series of new synthetic oleanane triterpenoids (SO) based on oleanolic acid as a starting material is reviewed, as is formation of biotin conjugates for investigation of protein targets. Expand
Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during acute viral hepatitis in mice.
TLDR
In vitro, hepatocytes from virally infected mice also were resistant to APAP-induced injury but sensitive to NAPQI, and acute viral hepatitis in this model resulted in selective down-regulation of APAP metabolizing P450s in liver and decreased the risk ofAPAP hepatotoxicity. Expand
A Synthetic Triterpenoid, CDDO-Me, Inhibits IκBα Kinase and Enhances Apoptosis Induced by TNF and Chemotherapeutic Agents through Down-Regulation of Expression of Nuclear Factor κB–Regulated Gene Products in Human Leukemic Cells
TLDR
It is suggested that CDDO-Me inhibits NF-κB through inhibition of IκBα kinase, leading to the suppression of expression of NF-σκB-regulated gene products and enhancement of apoptosis induced by TNF and chemotherapeutic agents. Expand
...
1
2
3
4
5
...