CYP450 enzymes

Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma (STS) that predominantly affects children and teenagers. It is the most common STS in children (40%) and accounts for 5-8% of total childhood malignancies. Apart from surgery and radiotherapy in eligible patients, standard chemotherapy is the only therapeutic option clinically available for RMS patients. While survival rates for this childhood cancer have considerably improved over the last few decades for low-risk and intermediate-risk cases, the mortality rate remains exceptionally high in high-risk RMS patients with recurrent and/or metastatic disease...

OBJECTIVES: The principal motive of this study is to explore the influence maternal separation (MS) exhibits on the mRNA expression of major drug metabolizing-cyp450s in parallel with the assessment of pathological changes that can be induced by MS in the livers of experimental mice. METHODS: Eighteen Balb/c mouse pups, comprising of both males and females, were separated from their mothers after birth. Following a six-week period during when the pups became adults, the mice were sacrificed and their livers were isolated for analysis of weight, pathohistological alterations, and the mRNA expression of drug metabolizing cyp450 genes: cyp1a1 , cyp3a11 , cyp2d9 , and cyp2c29 ...

Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients...

BACKGROUND: Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). METHODS: The mice were randomly separated into four groups ( n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks...

OBJECTIVE: To determine if a cytochrome (CYP) P450 enzyme inhibitor can maintain therapeutic plasma levels of voriconazole when administered orally. ANIMALS: 11 healthy, common ravens (Corvus corax). METHODS: Birds were randomly assigned to pilot study groups to receive voriconazole orally alone or combined with a CYP inhibitor. Pilot studies with 3 CYP inhibitors launched the main study using ciprofloxacin (20 mg/kg) followed 1 hour later by voriconazole (6 mg/kg) every 12 hours for 14 days...

Curcumin (CUR) is a natural product with known anti-inflammatory, antioxidant, and hepatoprotective properties. The aim of this study was to formulate CUR into a polymeric nanoparticle (NP) formulation and examine its potential hepatoprotective activity in an animal model of diclofenac (DIC)-induced hepatotoxicity. CUR was loaded into polymeric NPs composed of poly(ethylene glycol)-polycaprolactone (PEG-PCL). The optimal CUR NPs were evaluated against DIC-induced hepatotoxicity in mice, by studying the histopathological changes and gene expression of drug-metabolizing cyp450 ( cyp2c29 and cyp2d9 ) and ugt ( ugt2b1 ) genes in the livers of the animals...

Introduction: The lack of functional hepatocytes poses a significant challenge for drug safety testing and therapeutic applications due to the inability of mature hepatocytes to expand and their tendency to lose functionality in vitro . Previous studies have demonstrated the potential of Human Liver Stem Cells (HLSCs) to differentiate into hepatocyte-like cells within an in vitro rotary cell culture system, guided by a combination of growth factors and molecules known to regulate hepatocyte maturation. In this study, we employed a matrix multi-assay approach to comprehensively characterize HLSC differentiation...

Primary human hepatocytes (PHHs) are used extensively for in vitro liver cultures to study hepatic functions. However, limited availability and invasive retrieval prevent their widespread use. Induced pluripotent stem cells exhibit significant potential since they can be obtained non-invasively and differentiated into hepatic lineages, such as hepatocyte-like cells (iHLCs). However, there are concerns about their fetal phenotypic characteristics and their hepatic functions compared to PHHs in culture. Therefore, we performed an RNA-sequencing (RNA-seq) analysis to understand pathways that are either up- or downregulated in each cell type...

Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC...

Introduction: 7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats. Methods: Forty male albino rats were allocated into four equal groups (n = 10)...

CONTEXT: The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities. OBJECTIVES: The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use. MATERIALS AND METHODS: The experiments were conducted in pooled human liver microsomes (HLMs)...

Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20...

Nitrite and microplastics (MPs) are environmental pollutants that threaten intestinal integrity and affect immune function of shrimp. In this study, the shrimp Litopenaeus vannamei were exposed to the individual and combined stress of nitrite and microplastics for 14 days, and the changes of intestinal histology and physiological functions were investigated. After single and combined stress, affectations occurred in intestinal tissue; the antioxidant enzyme activities (MDA, H2 O2 , CAT increased) and gene expression levels (CAT, SOD, GPx, HSP70 up-regulated) changed...

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P...

Coal workers' pneumoconiosis (CWP) is one of the most common inhalation occupational diseases. It is no effective treatment methods. Early diagnosis of CWP could reduce mortality. Lipid mediators (LMs) as key mediators in the generation and resolution of inflammation, are natural biomarkers for diagnosis inflammatory disease, such as CWP. The UHPLC-MRM technique was used to detect LMs in urine. The metabolic network of LMs in CWP and CT group samples was comprehensively analyzed. Screening for major difference compounds between the two groups...

Gamisoyo-san is an herbal formula widely used to treat psychological issues, menopausal symptoms, and dysmenorrhea. However, there is insufficient information on its safety profile. This study aimed to confirm the genotoxic and acute toxic potential of Gamisoyo-san . We performed a battery of tests, which included a bacterial reverse mutation test (Ames test) using five bacterial strains, an in vitro chromosomal aberration test using Chinese hamster lung (CHL) cells, an in vivo micronucleus test in mice, and human Cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) assays...

Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) gene is one of the sub-members of CYP450 family member and it encodes with the families of drug metabolizing enzyme families along with the cancers and leukemias. Among leukemias, AML is considered to be one of the important leukemia which attack the older adults. The aim of this study is to explore the role of A4889G polymorphism in CYP1A1 gene in acute myeloid leukemia (AML) in the Saudi population. This study was designed as an experimental case-control study in which 100 AML cases and 100 controls were selected...

Dioscorea cirrhosa L. ( D. cirrhosa ) tuber is a traditional medicinal plant that is abundant in various pharmacological substances. Although diosgenin is commonly found in many Dioscoreaceae plants, its presence in D. cirrhosa remained uncertain. To address this, HPLC-MS/MS analysis was conducted and 13 diosgenin metabolites were identified in D. cirrhosa tuber. Furthermore, we utilized transcriptome data to identify 21 key enzymes and 43 unigenes that are involved in diosgenin biosynthesis, leading to a proposed pathway for diosgenin biosynthesis in D...

Understanding the interactions between different environmental pollutants is necessary in ecotoxicology since environmental contaminants never appear as single components but rather in combination with other substances. Heavy metals and pesticides are commonly detected in the environment, but the characterization of their mixture toxicity has been inadequately explored. This research aimed to elucidate the mixture impacts of the heavy metal lead (Pb) and the pesticide procymidone (PCM) on the hook snout carp (Opsariichthys bidens) using an array of biomarkers...

Decellularization of discarded whole livers and their recellularization with patient-specific induced pluripotent stem cells (iPSCs) to develop a functional organ is a promising approach to increase donor pool. The effect of extracellular matrix (ECM) of marginal livers on iPSC-hepatocyte differentiation and function has not been shown. To test the effect of donor liver ECM age and steatosis, we decellularized young, old, as well as no, low and high steatosis livers. All livers were decellularized successfully...