Clinical observations have suggested that cholestasis is associated with increased neurotransmission mediated by the opioid system in the central nervous system. As opiate agonists (e.g. morphine) mediate analgesia, increased opioidergic tone in cholestasis should be associated with a decreased response to pain. To test this hypothesis, the response of rats with acute cholestasis to a nociceptive stimulus was measured by the use of the tail-flick test, an extensively validated assay for measuring opiate-induced antinociception. Five and 7 days after bile-duct resection, the mean tail-flick latency was longer than before surgery (p < 0.05), whereas the corresponding means for unoperated and sham-resected controls were not significantly different from their respective baseline values. The increase in the mean tail-flick latency in the bile-duct resection group was reversed by (-)-naloxone (1 mg/kg subcutaneously), but not by its enantiomer (+)-naloxone (10 mg/kg subcutaneously) (p < 0.001). The stereoselective reversal of antinociception in cholestasis by naloxone indicates that this phenomenon is opioid-receptor mediated. In contrast, prolongation of the mean TFL found in the rat model of thioacetamide-induced acute hepatocellular necrosis was not reversed by (-)-naloxone, indicating that antinociception in this model is not opioid mediated. These findings provide support for the hypothesis that cholestasis is associated with increased opioidergic tone.
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http://dx.doi.org/10.1016/s0168-8278(05)80471-4 | DOI Listing |
J Intensive Med
January 2025
Department of Critical Care Medicine, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Background: Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still unclear.
View Article and Find Full Text PDFToxicol 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 PDFInflammation
January 2025
Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
Cholestasis is a multifactorial hepatobiliary disorder, characterized by obstruction of bile flow and accumulation of bile, which in turn causes damage to liver cells and other tissues. In severe cases, it can result in the development of life-threatening conditions, including cirrhosis and liver cancer. Paeoniflorin (PF) has been demonstrated to possess favourable therapeutic potential for the treatment of cholestasis.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Fengxian Hospital, Southern Medical University, Shanghai, China.
Background: In the past few decades, selective serotonin reuptake inhibitors (SSRIs) became widely used antidepressants worldwide. Therefore, the adverse reactions of patients after SSRI administration became a public and clinical concern. In this study, we conducted a pharmacovigilance study using the Adverse Event Reporting System (FAERS) database of the US Food and Drug Administration.
View Article and Find Full Text PDFBackground And Aims: Sarcoidosis is a multisystem disorder characterized by nonnecrotizing granulomas. Studies suggest 20%-70% of patients with sarcoidosis have abnormal liver chemistries or abdominal imaging. Hepatic sarcoidosis may be complicated by portal hypertension (portal HTN) with or without cirrhosis.
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