NAD AND Quinone

OBJECTIVES: Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained. METHODS: In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated. KEY FINDINGS: Different doses of trilobatin (5, 10 and 20 μM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells...

Paracoccus denitrificans has a classical cytochrome-dependent electron transport chain and two alternative oxidases. The classical transport chain is very similar to that in eukaryotic mitochondria. Thus, P. denitrificans can serve as a model of the mammalian mitochondrion that may be more tractable in elucidating mechanisms of regulation of energy production than are mitochondria. In a previous publication we reported detailed studies on respiration in P. denitrificans grown aerobically on glucose or malate...

OBJECTIVES: The study aimed to investigate the protective effects of dexmedetomidine (DEX) on renal injury caused by acute stress in rats and explore the protective pathways of DEX on rat kidneys in terms of oxidative stress. METHODS: An acute restraint stress model was utilized, where rats were restrained for 3 hours after a 15-minute swim. Biochemical tests and histopathological sections were conducted to evaluate renal function, along with the measurement of oxidative stress and related pathway proteins...

NAD(P)H-quinone oxidoreductase 1 (NQO1) is an essential redox enzyme responsible for redox balance and energy metabolism. Despite of its importance, the brain contains high capacity of polyunsaturated fatty acids and maintains low levels of NQO1 expression. In this study, we examined how levels of NQO1 expression affects cell survival in response to toxic insults causing mitochondrial dysfunction and ferroptosis, and whether NQO1 has a potential as a biomarker in different stressed conditions. Following treatment with rotenone, overexpressed NQO1 in SH-SY5Y cells improved cell survival by reducing mitochondrial reductive stress via increased NAD+ supply without mitochondrial biogenesis...

Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm)...

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice...

OBJECTIVES: Gentamicin is one of the most common ototoxic drugs that can lower patients' quality of life. Oxidative stress is a key factors inducing sensory hair cell death during gentamicin administration. So far, there are no effective drugs to prevent or treat gentamicin- induced hearing loss. A recent study found cystic fibrosis transmembrane conductance regulator (CFTR) as a new target to modulate cellular oxidative balance. The objective of this study was to estimate the effect of the CFTR activator ivacaftor on gentamicin-induced ototoxicity and determine its mechanism...

By controlling several antioxidant and detoxifying genes at the transcriptional level, including NAD(P)H quinone oxidoreductase 1 (NQO1), multidrug resistance-associated proteins (MRPs), UDP-glucuronosyltransferase (UGT), glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, glutathione S-transferase (GST), sulfiredoxin1 (SRXN1), and heme-oxygenase-1 (HMOX1), the KEAP1/NRF2 pathway plays a crucial role in the oxidative stress response. Accordingly, the discovery of modulators of this pathway, activating cellular signaling through NRF2, and targeting the antioxidant response element (ARE) genes is pivotal for the development of effective antioxidant agents...

The purpose of this study was to determine the efficacy of tannic acid on the antioxidative function, immunity, and intestinal barrier of broilers co-infected with coccidia and Clostridium perfringens (CCP). A total of 294 1-day-old arbor acres(AA) broilers were divided into three groups: control group (CON), CCP co-infected group (CCP), and 1000 mg/kg TA + CCP co-infected group (CTA). This trial lasted for 28 days. The results showed that the CCP group decreased the activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), catalase (CAT), and total antioxidant capacity (T-AOC) levels and increased the contents of hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA) in the jejunum ( p < 0...

In recent years, research on the discovery of natural compounds with potent antioxidant properties has resulted in growing interest in these compounds due to their potential therapeutic applications in oxidative-stress-related diseases. Argan oil, derived from the kernels of a native tree from Morocco, Argania spinosa , is renowned for its rich composition of bioactive compounds, prominently tocopherols, polyphenols, and fatty acids. Interestingly, a large body of data has shown that several components of argan oil activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, playing a crucial role in the cellular defense against oxidative stress...

Cadmium (Cd) and high molybdenum (Mo) are injurious to the body. Previous research has substantiated that Cd and Mo exposure caused testicular injury of ducks, but concrete mechanism is not fully clarified. To further survey the toxicity of co-exposure to Cd and Mo in testis, 40 healthy 8-day-old Shaoxing ducks (Anas platyrhyncha) were stochasticly distributed to 4 groups and raised with basic diet embracing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. At the 16th wk, testis tissues were gathered. The characteristic ultrastructural changes related to apoptosis and ferroptosis were observed in Mo or Cd or both groups...

Many studies have been conducted on the microbial reduction of Pd (II) to palladium nanoparticles (Pd-NPs) due to the environmental friendliness, low cost, and the decreased toxicity of Pd (II) ions. In this study, we investigate the reduction mechanism of Pd (II) by Bacillus megaterium Y-4 through proteomics. The data are available via ProteomeXchange with identifier PXD049711. Our results revealed that B. megaterium Y-4 may use the endogenous electron donor (NAD(P)H) generated by nirB, tdh, and fabG and reductase to reduce Pd (II) to Pd-NPs...

BACKGROUND: Inflammation is a biological response of the immune system to harmful stimuli. Penehyclidine hydrochloride (PCH) can alleviate inflammation and oxidative stress by activating reactive oxygen species (ROS), nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) in animal models, but there is a lack of cellular evidence. OBJECTIVES: This study investigated the effects of PHC on lipopolysaccharide (LPS)-induced inflammation response and oxidative stress in RAW264...

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production...

Accumulation of reactive oxygen species (i.e., oxidative stress) is a leading cause of beta cell dysfunction and apoptosis in diabetes. NRF2 (NF-E2 p45-related factor-2) regulates the adaptation to oxidative stress, and its activity is negatively regulated by the redox-sensitive CUL3 (cullin-3) ubiquitin ligase substrate adaptor KEAP1 (Kelch-like ECH-associated protein-1). Additionally, NRF2 is repressed by the insulin-regulated Glycogen Synthase Kinase-3 (GSK3). We have demonstrated that phosphorylation of NRF2 by GSK3 enhances β-TrCP (beta-transducin repeat-containing protein) binding and ubiquitylation by CUL1 (cullin-1), resulting in increased proteasomal degradation of NRF2...

Transcription factor NRF2 is involved in inflammatory reactions, maintenance of redox balance, metabolism of xenobiotics, and is of particular interest for studying aging. In the present work, the CRISPR/Cas9 genome editing technology was used to generate the NRF2ΔNeh2 mice containing a substitution of eight amino acid residues at the N-terminus of the NRF2 protein, upstream of the functional Neh2 domain, which ensures binding of NRF2 to its inhibitor KEAP1. Heterozygote NRF2wt/ΔNeh2 mice gave birth to homozygous mice with lower than expected frequency, accompanied by their increased embryonic lethality and visual signs of anemia...

Resveratrol has profound benefits against diabetes. However, whether its methylated derivative 3,4',5-trimethoxy- trans -stilbene (3,4',5-TMS) also plays a protective role in glucose metabolism is not characterized. We aimed to study the anti-diabetic effects of 3,4',5-TMS in vitro and in vivo . Insulin-resistant HepG2 cells (IR-HepG2) were induced by high glucose plus dexamethasone whilst six-week-old male C57BL/6J mice received a 60 kcal% fat diet for 14 weeks to establish an obese diabetic model. 3,4',5-TMS did not reduce the cell viability of IR-HepG2 cells at concentrations of 0...

BACKGROUND: Cardiotoxicity has been corroborated to be the toxic influence of cisplatin (CDDP). Oxidative stress and cardiomyocyte apoptosis play a vital part in cardiotoxicity induced by CDDP. Salvianolic acid Salvianolic acid B (SalB) is a monomeric component of Salvia miltiorrhiza, which has antioxidant and anti-inflammatory influences. In this research, we explored the mechanism of SalB in cardiotoxicity induced by CDDP. METHOD: 36 Wistar rats were separated into sham subgroup, CDDP (10 mg/kg) subgroup, CDDP (10 mg/kg) + SalB (1 μM) subgroup at random, CDDP (10 mg/kg) + SalB (5 μM) subgroup and CDDP (10 mg/kg) + SalB (10 μM) subgroup, Nicotinic Acid Riboside (NAR, 5 μM), with 6 rats in each subgroup...

Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis...

Deoxynivalenol (DON) is a common mycotoxin that is widely found in various foods and feeds, posing a potential threat to human and animal health. This study aimed to investigate the protective effect of the natural polyphenol piceatannol (PIC) against DON-induced damage in porcine intestinal epithelial cells (IPEC-J2 cells) and the underlying mechanism. The results showed that PIC promotes IPEC-J2 cell proliferation in a dose-dependent manner. Moreover, it not only significantly relieved DON-induced decreases in cell viability and proliferation but also reduced intracellular reactive oxygen species (ROS) production...