Kolinerjik Agonist Karbakolün Farede Parasetamolün Neden Olduğu Deneysel Hepatotoksisiteye Etkisi

Abstract

The effect of carbachol (CCh), which is a cholinomimetic agent, on paracetamol-induced hepatotoxicity in mice was evaluated in vivo. In addition, the effectiveness of N-acetylcysteine (NAC) as an antidote in APAP-related poisoning and the effectiveness of CCh were compared. In the toxicity of paracetamol (APAP), the production of N-acetyl-p-benzoquinone imine (NAPQI), which is a toxic metabolite of paracetamol for hepatocytes, increases. The antidote effect of NAC is due to its function as a precursor of GSH, which detoxifies NAPQI. Studies in the literature show that the parasympathomimetic effect may contribute positively to paracetamol toxicity through many mechanisms. In this study, NAC, CCh, and NAC+CCh were administered to mice with APAP toxicity. Mesenteric artery and portal vein blood flow were measured. AST, ALT, TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17, levels were measured and an increase was observed in APAP toxicity. The increases were mild relatively in the groups administered NAC, CCh, NAC+CCh. In addition to these parameters, TAS, TOS, GSH, GSSG levels were also measured in the study. After APAP toxicity, a decrease in antioxidant molecules, an increase in oxidant molecules, and oxidative stress index were observed. In the groups administered NAC, CCh, NAC+CCh, it was found that the decrease in antioxidant molecules, the increase in oxidant molecules and the oxidative stress index were less. Results consistent with biochemical findings were obtained in histopathological evaluations. In APAP-induced hepatotoxicity, the parasympathomimetic stimulation can be protective through many different mechanisms such as reducing inflammation, activating antioxidant pathways.