sildenafil-citrate and Cholestasis--Intrahepatic

Intrahepatic cholestasis is a common pathological condition of several types of liver disorders. In this study, we aimed to investigate the regulatory effects of quercetin (QU) on selected phosphodiesterase inhibitors against alpha-naphthyl isothiocyanate (ANIT)-induced acute intrahepatic cholestasis.. Cholestasis was induced in Wistar albino rats by ANIT as a single dose (60 mg/kg; P·O.). QU (50 mg/kg, daily, P·O.), sildenafil (Sild; 10 mg/kg, twice daily, P·O.), and pentoxifylline (PTX; 50 mg/kg, daily, P.O.) were evaluated either alone or in combinations for 10 days for their antioxidant, anti-inflammatory, and anti-pyroptotic effects.. ANIT produced a prominent intrahepatic cholestasis as evidenced by a significant alteration in liver functions, histological structure, inflammatory response, and oxidative stress biomarkers. Furthermore, up-regulation of NF-κB-p65, TLR4, NLRP3, cleaved caspase-1, IKK-β, and IL-1β concurrently with down-regulation of Nrf-2, HO-1, and PPAR-γ expressions were observed after ANIT. QU, Sild, or PTX treatment significantly alleviated the disturbance induced by ANIT. These findings were further supported by the improvement in histopathological features. Additionally, co-administration of QU with Sild or PTX significantly improved liver defects due to ANIT as compared to the individual drugs.. Combined QU with Sild or PTX exhibited promising hepatoprotective effects and anti-cholestatic properties through modulation of Nrf2/ARE, TLR4/NF- κB, and NLRP3/IL-1β signaling pathways.

Topics: Cholestasis; Cholestasis, Intrahepatic; Interleukin-1beta; Liver; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pentoxifylline; Quercetin; Rats; Signal Transduction; Sildenafil Citrate; Toll-Like Receptor 4

Topics: Cholestasis, Intrahepatic; Humans; Liver; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

We describe a patient with a hepatotoxic reaction, presenting with general malaise, severe jaundice, and pruritus. This turned out to be caused by the, at first unrevealed, use of sildenafil. The injury seems to be hepatocanalicular, characterized by a hepatocellular liver test pattern, combined with extensive cholestasis on liver biopsy. One should bare in mind that the use of sildenafil may not be readily disclosed by the patient nor his doctor.

Topics: Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Pruritus; Purines; Sildenafil Citrate; Sulfones; Truth Disclosure