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Abstract

We investigated the effects of the calcium-channel blocker verapamil hydrochloride on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 min by portal vein occlusion. Animals were pretreated with intravenous injection of verapamil hydrochloride (2.5 mg/kg) 5 min before vascular clamp. Verapamil hydrochloride limited increases in the chemoattractant compared with nonpretreated rats. Most cells immunostained for chemoattractant were ED2-positive macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with verapamil hydrochloride was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hr after reperfusion in nonpretreated animals, while pretreatment with verapamil hydrochloride significantly decreased chemoattractant mRNA levels. In vitro chemoattractant production could be induced in naive Kupffer cells after stimulation with oxygen radicals generated by hypoxanthine and xanthine oxidase, but verapamil hydrochloride prevented these increases. We concluded that the calcium-channel blocker verapamil hydrochloride significantly attenuates chemoattractant release by Kupffer cells after ischemia-reperfusion in the rat liver.

An Evaluation of Ischaemic Preconditioning as a Method of Reducing Ischaemia Reperfusion Injury in Liver Surgery and Transplantation

“…Kupffer Cells are resident liver macrophages and have been shown to be activated early following IR injury [ 92 , 93 ]. However experiments blocking macrophage activity have had varied results with some studies demonstrating that Kupffer cell blockade or modulation attenuated IR injury [ 94 , 95 ] whilst other models have shown increased IR injury following Kupffer cell depletion [ 96 ].…”

“…Treatment of mice with recombinant IL-10 prior to IR injury significantly attenuated IR injury and interestingly was associated with a reduction in TNFα production in the liver [ 105 ]. IL-10 depletion has been shown to result in increased liver injury and increased production of TNFα and IL-6 (89) [ 95 ] again demonstrating an interplay between these pro-inflammatory and anti-inflammatory cytokines and suggesting that manipulating cytokine production could alter IR injury. The effect of IPC on IL-10 levels post IR injury have been conflicting.…”

The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams–Beuren Syndrome Mouse Model

“…Although the participation of XOR in WBS has not been reported yet; however, other connective tissue diseases, such as Loeys-Dietz and Marfan syndromes, are associated with increased XOR protein levels in aortic samples [ 16 , 17 ]. Interestingly, ROS generated by hypoxanthine and xanthine oxidase can be inhibited by curcumin (CUR) [ 18 ] as well as verapamil hydrochloride (VER) [ 19 ].…”

Curcumin combined with verapamil improve cardiovascular phenotype of a Williams-Beuren Syndrome mice model reducing oxidative stress

“…Although the participation of XOR in WBS is unknown, related diseases as Loeys-Dietz and Marfan syndromes showed XOR protein levels increased in aortic samples (Soto et al, 2020; Rodríguez-Rovira et al, 2022). Previous studies have reported that ROS generated by hypoxanthine and xanthine oxidase were inhibited by curcumin (Akter et al, 2020) and the calcium channel blocker verapamil hydrochloride (Liang et al, 2000).…”