Liver enzymes

In human, the cytochrome P450 3A (CYP3A) subfamily of drug-metabolizing enzymes (DMEs) is responsible for a significant number of phase I reactions, with the CYP3A4 isoform superintending the hepatic and intestinal metabolism of diverse endobiotic and xenobiotic compounds. The CYP3A4-dependent bioactivation of chemicals may result in hepatotoxicity and trigger carcinogenesis. In cattle, four CYP3A genes (CYP3A74, CYP3A76, CYP3A28 and CYP3A24) have been identified. Despite cattle being daily exposed to xenobiotics (e...

OBJECTIVES: Gamete and embryo-foetal origins of adult diseases hypothesis proposes that adulthood chronic disorders are associated with adverse foetal and early life traits. Our study aimed to characterise developmental changes and underlying mechanisms of metabolic disorders in offspring of pre-eclampsia (PE) programmed pregnancy. METHODS: Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) induced pre-eclampsia-like C57BL/6J mouse model was used. Lipid profiling, histological morphology, indirect calorimetry, mRNA sequencing, and pyrosequencing were performed on PE offspring of both young and elderly ages...

The Siberian frog Rana amurensis has a uniquely high tolerance to hypoxia among amphibians, as it is able to withstand several months underwater with almost no oxygen (0.2 mg/liter) vs. several days for other studied species. Since it was hypothesized that hypoxia actives the antioxidant defense system in hypoxia-tolerant animals, one would expect similar response in R. amurensis. Here, we studied the effect of hypoxia in the Siberian frog based on the transcriptomic data, activities of antioxidant enzyme, and content of low-molecular-weight antioxidants...

Polybrominated diphenyl ethers (PBDEs) are legacy flame retardants that bioaccumulate in the environment. The gut microbiome is an important regulator of liver functions including xenobiotic biotransformation and immune regulation. We recently showed that neonatal exposure to polybrominated diphenyl ether-99 (BDE-99), a human breast milk-enriched PBDE congener, up-regulated pro-inflammation- and down-regulated drug metabolism-related genes predominantly in males in young adulthood. However, the persistence of dysregulation into late adulthood, differential impact of hepatic cell types, and the involvement of the gut microbiome from neonatal BDE-99 exposure remains unknown...

BACKGROUND: Sepsis is often accompanied by multiple organ dysfunction, in which the incidence of cardiac injury is about 60%, and is closely related to high mortality. Recent studies have shown that Golgi stress is involved in liver injury, kidney injury, and lung injury in sepsis. However, whether it is one of the key mechanisms of sepsis-induced cardiomyopathy (SIC) is still unclear. The aim of this study is to investigate whether Golgi stress mediates SIC and the specific mechanism...

Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella...

Drug-induced liver injury (DILI) presents a significant challenge in clinical practice, particularly with the rising popularity of herbal and dietary supplements (HDS) in the United States. Tongkat Ali (Eurycoma longifolia Jack), a Southeast Asian herb, has garnered attention for its purported health benefits, including enhancing testosterone levels. Here, we present a case of a 47-year-old male with acute liver injury following Tongkat Ali use, the first reported case of its kind in the literature. The patient exhibited worsening scleral icterus, elevated liver enzymes, and jaundice shortly after initiating Tongkat Ali supplementation, prompting hospitalization and subsequent clinical improvement upon discontinuation of the supplement...

The use of tyrosine kinase inhibitors (TKIs) has become the mainstay of treatment in patients suffering from chronic myeloid leukemia (CML), an adult leukemia caused by a reciprocal translocation between chromosomes 9 and 22, which creates an oncogene resulting in a myeloproliferative neoplasm. These drugs function by inhibiting the ATP-binding site on the fusion oncoprotein and subsequently halting proliferative activity. The goal of this work is to investigate the current state of research into genetic factors that influence the efficacy of four FDA-approved TKIs used to treat CML...

Serious iatrogenic vascular injuries are considered uncommon; however, they are underreported. There are limited studies discussing the proper management of these injuries; therefore, the management is often anecdotal. A 4-month-old female patient presented with elevated liver enzymes and cholecystitis with sludge. Her HIDA scan suggested biliary atresia. During the surgery, there was a bilateral iatrogenic injury to the hepato-duodenal ligament, including the portal vein, hepatic artery, and bile ducts. The patient underwent splenectomy and cholecystectomy, and the hepatic artery transection was successfully managed with a splenic artery jump graft and a portal vein bypass initiated with the SMV using a Gore-TexⓇ vascular graft...

Background Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART. Methods Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during regular follow-up...

BACKGROUND: Anthracyclines such as doxorubicin (Dox) are highly effective anti-tumor agents, but their use is limited by dose-dependent cardiomyopathy and heart failure. Our laboratory previously reported that induction of cytochrome P450 family 1 (Cyp1) enzymes contributes to acute Dox cardiotoxicity in zebrafish and in mice, and that potent Cyp1 inhibitors prevent cardiotoxicity. However, the role of Cyp1 enzymes in chronic Dox cardiomyopathy, as well as the mechanisms underlying cardioprotection associated with Cyp1 inhibition, have not been fully elucidated...

Pyruvate kinase is a glycolytic enzyme that converts phosphoenolpyruvate and ADP into pyruvate and ATP. There are two genes that encode pyruvate kinase in vertebrates; Pkm and Pkl encode muscle- and liver/erythrocyte-specific forms, respectively. Each gene encodes two isoenzymes due to alternative splicing. Both muscle-specific enzymes, Pkm1 and Pkm2, function in glycolysis, but Pkm2 also has been implicated in gene regulation due to its ability to phosphorylate histone 3 threonine 11 (H3T11) in cancer cells...

BACKGROUND: Tuberculosis is still one of the biggest causes of infection-related death around the world. Disseminated tuberculosis is a potentially fatal disease caused by the haematogenous spread of Mycobacterium tuberculosis. First-line anti-tuberculosis drugs in-clude isoniazid, rifampicin, pyrazinamide, and ethambutol. The first three drugs are known to cause hepatotoxicity. CASE PRESENTATION: We have, herein, reported a case of Drug-induced Liver Injury (DILI) due to anti-tuberculosis therapy in a one-year-old male child with disseminated tuberculosis...

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Human cytochrome P450 3A4 (CYP3A4) is a drug-metabolizing enzyme that is abundantly expressed in the liver and intestine. It is an important issue whether compounds of interest affect the expression of CYP3A4 because more than 30% of commercially available drugs are metabolized by CYP3A4. In this study, we examined the effects of cholesterol and cholic acid on the expression level and activity of CYP3A4 in hCYP3A mice that have a human CYP3A gene cluster and show human-like regulation of the coding genes. A normal diet (ND, CE-2), CE-2 with 1% cholesterol and 0...

This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned...

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction...

Interspecific interactions are central to ecological research. Plants produce toxic plant secondary metabolites (PSMs) as a defense mechanism against herbivore overgrazing, prompting their gradual adaptation to toxic substances for tolerance or detoxification. P450 enzymes in herbivore livers bind to PSMs, whereas UDP-glucuronosyltransferase and glutathione S-transferase increase the hydrophobicity of the bound PSMs for detoxification. Intestinal microorganisms such as Bacteroidetes metabolize cellulase and other macromolecules to break down toxic components...

BACKGROUND: Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients. METHODS: The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English...

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is associated with altered gut microbiota; however, there has been a focus on fecal samples, which are not representative of the entire digestive tract. Mucosal biopsies of the descending duodenum were collected. Five regions of the 16S rRNA gene were amplified and sequenced. Other assessments conducted on the study subjects included body mass index, transient elastography, liver enzymes, and lipid profile...