Treatment Of ROS-related Diseases Research Articles

Aptamer-modified atomically precise gold nanoclusters as targeted nanozymes to scavenge reactive oxygen species in white adipocytes

Oxidative stress caused by excessive reactive oxygen species (ROS) leads to the dysfunction of white adipocytes and white fat, and also promotes triglyceride storage by inhibiting the respiration of adipocytes directly. Nanozymes, as a new generation of artificial enzymes, have exhibited attractive potential in scavenging ROS and treatment of ROS-related diseases. Herein, aptamer-modified atomically precise gold Au25 nanoclusters (Apt-Au25 NCs), are employed as targeted nanozymes to scavenge ROS in white adipocytes. Our results show that Apt-Au25 NCs have high targeting capability toward white adipocytes with low cytotoxicity. Furthermore, Apt-Au25 NCs show high superoxide dismutase (SOD)-like and catalase (CAT)-like activity in a concentration-dependent manner, and also good thermal and pH stability compared with natural SOD and CAT. Finally, the efficiency of ROS scavenging by Apt-Au25 NCs in white adipocytes is evaluated. This work demonstrates that Apt-Au25 NCs, as targeted nanozymes, are efficient in scavenging ROS in white adipocytes, exhibiting promising potential for the treatment of obesity and related diseases.

Multienzymatic Antioxidant Activity of Manganese-Based Nanoparticles for Protection against Oxidative Cell Damage.

Oxidative stress is related to many diseases, but available clinical treatment methods are currently limited. Exploitation of enzyme-mimicking nanomaterials (nanozymes) is a promising way for scavenging reactive oxygen species (ROS) and treatment of ROS-related diseases. Herein, the catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) mimicking activities are expressed by MnO2 nanoparticles (MnO2-BSA NPs) coated with BSA. Effective •OH removal activity is also expressed by MnO2-BSA NPs at neutral pH. Apoptosis inhibition and ROS scavenging capabilities of MnO2-BSA NPs are evident on the H2O2-exposed BEAS-2B cells line. Western blot analysis indicates that MnO2-BSA NPs inhibit H2O2-induced apoptosis by mediating the expression of apoptosis-related proteins.

Study on a 65-mer peptide mimetic enzyme with GPx and SOD dual function.

Excessive reactive oxygen species (ROS) levels are harmful to the body. The peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant enzymes for preventing ROS-induced damage. Se-CuZn-65P is an enzyme mimetic with dual GPx and SOD antioxidant function. However, currently, its production is mainly based on the cysteine auxotrophic expression technique, which is inefficient, expensive, and time consuming. In this study, we combined protein engineering and the chemical mutation method to synthesize Se-CuZn-65P. The DNA sequence encoding the 65 amino acid peptide with the desired sequence transformations to incorporate the SOD and the GPx catalytic sites was cloned and expressed in a soluble protein expression vector. The protein yield increased up to 152mg/L, which is 10 times higher than in previous studies. The SOD and GPx activity of Se-CuZn-65P was high (1181U/mg and 753U/μmol, respectively). The binding constant of glutathione was 5.6×104 L·mol-1 , which shows that Se-CuZn-65P efficiently catalyzed hydrogen peroxide reduction by glutathione. Mitochondrial damage experiments confirmed the double protective role of the Se-CuZn-65P peptide and demonstrated functional synergy between the SOD and the GPx domains, which indicates its potential to be used in the treatment of ROS-related diseases. Our research may give a new thought to increase the yield of mimic.

Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone

BackgroundAcute liver damage is primarily induced by one of several causes, among them viral exposure, alcohol consumption, and drug and immune system issues. Agents with the ability to inhibit tyrosinase and protect against DNA damage caused by reactive oxygen species (ROS) may be therapeutically useful for the prevention or treatment of ROS-related diseases. MethodsThis investigation examined the hepatoprotective effects of phloretin and phloretin isonicotinyl hydrazone (PIH) on d-galactosamine (D-GalN)-induced acute liver damage in Kunming mice, as well as the possible mechanisms. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (TB) as well as the histopathological changes in mouse liver sections were determined. The antioxidant effects of phloretin, quercetin, and PIH on lipid peroxidation in rat liver mitochondria in vitro, 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA were confirmed. The experiment also examined the antityrosinase activity, inhibition type, and inhibition constant of phloretin and PIH. ResultsPhloretin, quercetin, or PIH significantly prevented the increase in serum ALT, AST, γ-GT, ALP, and TB in acute liver damage induced by D-GalN, and produced a marked reduction in the histopathological hepatic lesions. Phloretin, quercetin, or PIH also exhibited antioxidant effects on lipid peroxidation in rat liver mitochondria in vitro, DPPH or ABTS free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA. Phloretin, quercetin, or PIH also exhibited good antityrosinase activity. ConclusionTo the best of our knowledge, this was the first study of the hepatoprotective effects of phloretin and PIH on D-GalN-induced acute liver damage in Kunming mice as well as the possible mechanisms. This was also the first study of the lipid peroxidation inhibition activity of phloretin and PIH in liver mitochondria induced by the Fe2+/vitamin C (Vc) system in vitro, the protective effects on supercoiled pBR322 plasmid DNA, and the antityrosinase activity of phloretin and PIH.

The Principle and the Potential Approach to ROS-dependent Cytotoxicity by Non-pharmaceutical Therapies: Optimal Use of Medical Gases with Antioxidant Properties

Regulation of cellular redox balances is important for the homeostasis of human health. Thus, many important human diseases, such as inflammation, diabetes, glaucoma, cancers, ischemia and neurodegenerative diseases, have been investigated in the field of reactive oxygen species (ROS) and oxidative stress. To overcome the harmful effect of oxidative stress and ROS, one can directly eliminate them by medical gases such as carbon monoxide (CO), hydrogen sulphide (H(2)S), and molecular hydrogen (H(2)), or one can induce ROS-resistant proteins and antioxidant enzymes to antagonize oxidative stresses. This article reviews the molecular mechanisms how these medical gasses work as antioxidants, and how ROS resistant proteins are produced in the physiological context. Targeted therapeutic modalities to scavenge or prevent ROS might be applied in the prevention and treatment of ROS-related diseases in the near future.