New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

Krajewska, Julia; Włodarczyk, Jakub; Jacenik, Damian; Kordek, Radzisław; Taciak, Przemysław; Szczepaniak, Remigiusz; Fichna, Jakub

doi:10.3390/ijms22063121

Cited by 8 publications

(16 citation statements)

References 48 publications

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“…A new gold (III) complex was designed and screened in in vitro studies, using a mouse macrophage cell line, RAW264.7, as well as in vivo, in a dextran sulfate sodium (DSS)-induced mouse model of colitis [ 32 , 33 ]. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, the complex showed a potent anti-inflammatory profile, as evidenced in neutral red uptake and Griess tests.…”

Section: Inflammatory Bowel Diseases (Ibd)mentioning

confidence: 99%

“…Moreover, the gold (III) complex induced changes in the tight junction complex expression in the intestinal wall. This is the first study proving that gold (III) complexes may have therapeutic potential in the treatment of IBD [ 32 ]. On the other hand, oral gold nanoparticles (5 nm, 25 μg/kg) can prevent colitis by attenuating the inflammatory response mediated by Toll-like receptor 4 and reactive oxygen/nitrogen substances, but may lead to imbalance of the intestinal flora of mice [ 34 ].…”

Section: Inflammatory Bowel Diseases (Ibd)mentioning

confidence: 99%

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Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

Wang

Hsiao

et al. 2022

Molecules

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Gold has always been regarded as a symbol of nobility, and its shiny golden appearance has always attracted the attention of many people. Gold has good ductility, molecular recognition properties, and good biocompatibility. At present, gold is being used in many fields. When gold particles are as small as several nanometers, their physical and chemical properties vary with their size in nanometers. The surface area of a nano-sized gold surface has a special effect. Therefore, gold nanoparticles can, directly and indirectly, give rise to different biological activities. For example, if the surface of the gold is sulfided. Various substances have a strong chemical reactivity and are easy to combine with sulfhydryl groups; hence, nanogold is often used in biomedical testing, disease diagnosis, and gene detection. Nanogold is easy to bind to proteins, such as antibodies, enzymes, or cytokines. In fact, scientists use nanogold to bind special antibodies, as a tool for targeting cancer cells. Gold nanoparticles are also directly cytotoxic to cancer cells. For diseases caused by inflammation and oxidative damage, gold nanoparticles also have antioxidant and anti-inflammatory effects. Based on these unique properties, gold nanoparticles have become the most widely studied metal nanomaterials. Many recent studies have further demonstrated that gold nanoparticles are beneficial for humans, due to their functional pharmacological properties in a variety of diseases. The content of this review will be the application of gold nanoparticles in treating or diagnosing pressing diseases, such as cancers, retinopathy, neurological diseases, skin disorders, bowel diseases, bone cartilage disorders, cardiovascular diseases, infections, and metabolic syndrome. Gold nanoparticles have shown very obvious therapeutic and application potential.

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Section: Inflammatory Bowel Diseases (Ibd)mentioning

confidence: 99%

Section: Inflammatory Bowel Diseases (Ibd)mentioning

confidence: 99%

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

Wang

Hsiao

et al. 2022

Molecules

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“…Additionally, colon weight was decreased for DSS-only treated mice (0.39 ± 0.01 g vs. 0.50 ± 0.03 g for control animals), while mice treated with the lowest dose of OAT-177 showed colon weight comparable to the control group (0.47 ± 0.02 g) (Figure 1C). The MPO activity represents neutrophil infiltration of the intestine; therefore, it is the highest in the inflamed tissue [18]. In line, the MPO activity was lowest in the colon of control animals (2.48 ± 0.38 U) and DSS-treated mice, which received OAT-177 at the lowest dose (2.46 ± 0.55 U).…”

Section: Oat-177mentioning

confidence: 71%

The Anti-Inflammatory Effect of Acidic Mammalian Chitinase Inhibitor OAT-177 in DSS-Induced Mouse Model of Colitis

Mazur

Włodarczyk

Świerczyński

et al. 2022

IJMS

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Inflammatory bowel diseases (IBD) are chronic and relapsing gastrointestinal disorders, where a significant proportion of patients are unresponsive or lose response to traditional and currently used therapies. In the current study, we propose a new concept for anti-inflammatory treatment based on a selective acidic mammalian chitinase (AMCase) inhibitor. The functions of chitinases remain unclear, but they have been shown to be implicated in the pathology of various inflammatory disorders regarding the lung (asthma, idiopathic pulmonary fibrosis) and gastrointestinal tract (IBD and colon cancer). The aim of the study is to investigate the impact of AMCase inhibitor (OAT-177) on the dextran sulfate sodium (DSS)-induced models of colitis. In the short-term therapeutic protocol, OAT-177 given intragastrically in a 30 mg/kg dose, twice daily, produced a significant (p < 0.001) anti-inflammatory effect, as shown by the macroscopic score. Additionally, OAT-177 significantly decreased TNF-α mRNA levels and MPO activity compared to DSS-only treated mice. Intraperitoneal administration of OAT-177 at a dose of 50 mg/kg caused statistically relevant reduction of the colon length. In the long-term therapeutic protocol, OAT-177 given intragastrically in a dose of 30 mg/kg, twice daily, significantly improved colon length and body weight compared to DSS-induced colitis. This is the first study proving that AMCase inhibitors may have therapeutic potential in the treatment of IBD.

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“…The novel Au(III) compound turned out to exert cytostatic/cytotoxic effects in cancer Ha-Ras transfected NIH3T3 fibroblasts selectively in comparison to the noncancer NIH3T3 cells ( Table 5 ). Since Ras isoforms share 80% identity and share similar activity—one can conclude that in CRC with Ras hyperactivation (mostly K-Ras) (like HCT116), the compound TGS121 would also be effective [ 124 , 125 ].…”

Section: In Vitro Studiesmentioning

confidence: 99%

Gold (III) Derivatives in Colon Cancer Treatment

Gurba

Taciak

Sacharczuk

et al. 2022

IJMS

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Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

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New Class of Anti-Inflammatory Therapeutics Based on Gold (III) Complexes in Intestinal Inflammation–Proof of Concept Based on In Vitro and In Vivo Studies

Cited by 8 publications

References 48 publications

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications

The Anti-Inflammatory Effect of Acidic Mammalian Chitinase Inhibitor OAT-177 in DSS-Induced Mouse Model of Colitis

Gold (III) Derivatives in Colon Cancer Treatment

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