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POSSIBLE PROTECTIVE EFFECT OF NICARDIPINE ON ANIT INDUCE CHOLESTASIS IN RAT

DOAA ADNAN ATSHAN 1*, MUNAF HASHIM ZALZALA 2

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Cholestasis is a hepatobiliary condition that can manifest as acute or chronic, resulting from disruptions in the normal bile flow, formation or secretion processes. Inflammation, dysregulation of bile acid transporters and oxidative stress play significant roles in the development of cholestasis. Nicardipine is classified as a dihydropyridine calcium channel blocker. According to reports, nicardipine exhibits an affinity for the FXR receptor. This paper aims to study its protection against cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in rats. Thirty male albino rats were divided into three groups, each with ten rats. Group I (control) received 1 mL/kg corn oil 48 hours before euthanasia; group II were orally administered 100 mg/kg ANIT. Group III received a 24 mg/kg dosage of nicardipine over seven consecutive days. A single dose of ANIT at a concentration of 100 mg/kg was orally administered on the fifth day; group II and III animals were euthanized 48 hours after inducing cholestasis. Nicardipine administration resulted in reduced levels of liver enzymes (ALT, AST, ALP, GGT), bilirubin, and bile acids. Additionally, antioxidant levels (SOD, GSH) increased, while inflammatory markers (TNF-α, IL-1β) decreased. Nicardipine upregulated expression of FXR, HNF1α, SHP, and BSEP, suggesting improved bile metabolism. Moreover, it enhanced antioxidative gene expressions (Nrf-2, Nqo-1, HO-1), reinforcing its hepatoprotective potential. In summary, nicardipine demonstrates promise in mitigating ANIT-induced hepatotoxicity and cholestasis, possibly through modulation of bile acid metabolism, antioxidative pathways, and inflammation. These findings warrant further exploration of nicardipine's therapeutic role in hepatobiliary disorders.