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Mechanisms involved in the valproic acid-induced hepatotoxicity: A Comprehensive review.
Toxicol Mech Methods
January 2025
Department of Pharmacology, SVKM's NMIMS School of Pharmacy and Technology Management, Babulde, Shirpur, 425405 Maharashtra, India.
Adverse drug reactions (ADR) remain a challenge in modern healthcare, particularly given the increasing complexity of therapeutics. WHO's definition of an adverse drug reaction as a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. This definition underscores the importance of monitoring and mitigating unintended drug effects, particularly for widely used medications like valproic acid (VPA).
View Article and Find Full Text PDFThrough biochemical transformation of host-derived bile acids (BAs), gut bacteria mediate host-microbe crosstalk and sit at the interface of nutrition, the microbiome, and disease. BAs play a crucial role in human health by facilitating the absorption of dietary lipophilic nutrients, interacting with hormone receptors to regulate host physiology, and shaping gut microbiota composition through antimicrobial activity. Bile acid deconjugation by bacterial bile salt hydrolase (BSH) has long been recognized as the first necessary BA modification required before further transformations can occur.
View Article and Find Full Text PDFMaternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.
Liver Int
February 2025
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.
Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.
Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.
Comparative Analysis of γ-Cyclodextrin, Perilla Oil, and Their Inclusion Complexes on Liver Injury and Dyslipidemia Associated with Elevated Gastrointestinal 12-Hydroxylated Bile Acid Levels.
Molecules
January 2025
Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, Japan.
Our previous study demonstrated that γ-cyclodextrin (γ-CD)-perilla oil inclusion complexes increase plasma α-linolenic acid and eicosapentaenoic acid levels in healthy rats without adverse effects. The present study examined the effects of perilla oil, γ-CD, and their inclusion complexes on rats fed cholic acid (CA) to mimic the elevated gastrointestinal 12-hydroxylated (12OH) bile acid levels in high-fat diet-fed rats. Rats fed CA (CA group) tended to have higher AST, ALT, plasma total cholesterol (T-CHO), and triglyceride (TG) levels compared to controls fed a standard diet without CA.
View Article and Find Full Text PDFEvidence for the Worldwide Distribution of a Bile Salt Hydrolase Gene in Through Horizontal Gene Transfer.
Int J Mol Sci
January 2025
Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8566, Ibaraki, Japan.
Bile salt hydrolase (BSH), a probiotic-related enzyme with cholesterol-assimilating and anti-hypercholesterolemic abilities, has been isolated from intestinal bacteria; however, BSH activity of bacteria in bile-salt-free (non-intestinal) environments is largely unknown. Here, we aimed to identify BSH from non-intestinal and characterize its enzymatic function. We successfully isolated a plasmid-encoded () from , and the recombinant EfpBSH showed BSH activity that preferentially hydrolyzed taurine-conjugated bile salts, unlike the activity of known BSHs.
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