The College of Pharmacy discussed the PhD dissertation entitled “Evaluation of the Protective Effect of Two Doses of Papaverine and Nicardipine Against Alpha-Naphthylisothiocyanate Induced Cholestasis in Male Rats” by the student Doaa Adnan Atshan and the supervisor, Professor Dr. Prof.Dr.Munaf Hashim Abdulrazzaq, at the Pharmacology and Toxicology Department. This study aimed to evaluate the possible protective effects of two doses of papaverine and nicardipine on cholestasis induced by alpha-naphthylisothiocyanate in male rats. The study included sixty male albino rats divided into six groups, each with ten rats. Group I rats (control) were administered 1 mL/kg corn oil 48 hours before sacrifice; group II rats were orally administered 100 mg/kg alpha-naphthylisothiocyanate 48 hours before sacrifice. Group III and IV received 100 and 200 mg/kg of papaverine, respectively, over seven consecutive days. Groups V and VI received a 12 and 24 mg/kg dosage of nicardipine, respectively, over seven consecutive days. A single dose of alpha-naphthylisothiocyanate at a concentration of 100 mg/kg was orally administered on the fifth day for groups III, IV, V, and VI, then euthanized 48 hours after inducing cholestasis, and the serum was obtained for biochemical analysis for liver function tests, total bilirubin, and bile acid, while the liver utilized for assessing oxidative stress, pro-inflammatory parameters, the farnesoid x receptor, the nuclear factor erythroid 2-related factor 2 signaling pathway, and histopathological analysis. The result showed that oral administration of papaverine and nicardipine before alpha-naphthylisothiocyanate significantly improved liver function tests, total bilirubin, and bile acid. Furthermore, papaverine and nicardipine inhibited alpha-naphthylisothiocyanate, which induced hepatic oxidative stress. Papaverine and nicardipine inhibited alpha-naphthylisothiocyanate-induced inflammatory mediators. Hepatic mRNA levels of both the farnesoid X receptor and the nuclear factor erythroid 2-related factor 2 signaling pathway were upregulated following high papaverine and nicardipine doses, including the farnesoid X receptor, bile salt export pump, hepatocyte nuclear factor-1 alpha, small heterodimer partner, nuclear factor erythroid 2-related factor 2, heme oxygenase, and NAD(P)H:quinone-oxidoreductase-1. Western blot analysis showed an increase in farnesoid X receptor, bile salt export pump, heme oxygenase, and sirtuin levels. The study recommended the treatment with papaverine and nicardipine, which has a promising pharmacological intervention in inhibiting cholestasis in a rat’s model.
