Ameliorative effects of umbelliferone against acetaminophen-induced hepatic oxidative stress and inflammation in mice

Saeed Sadeghinejad, Mehrnoosh Mousavi, Leila Zeidooni, Esrafil Mansouri, Shokooh Mohtadi, Mohammad Javad Khodayar

Abstract


Background and purpose: Acetaminophen (APAP) is a commonly used antipyretic and pain reliever                             that its overdose causes acute liver toxicity. Umbelliferone (UMB) has many pharmacological effects.                                In this study, the hepatoprotective effect of UMB on acute hepatotoxicity induced by APAP was                    investigated.

Experimental approach: Forty-nine male mice were separated into seven groups. The control received vehicle (i.p.), UMB group received UMB (120 mg/kg, i.p.), APAP group was treated with a single dose of APAP (350 mg/kg, i.p.), and pretreated groups received N-acetylcysteine (NAC, 200 mg/kg, i.p.) or different doses of UMB (30, 60, and 120 mg/kg, i.p.), respectively before APAP. Twenty-four hours after APAP injection, mice were sacrificed and blood and liver samples were collected. Then, serum and tissue samples were investigated for biochemical and histological studies.

Findings/Results: A single dose of APAP caused elevation in the serum liver enzymes, including                         alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The amounts of thiobarbituric                                   acid reactive substances, tumor necrosis factor-alpha, and nitric oxide increased in the mice’s liver                             tissue. Moreover, the amount of total thiol and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) significantly diminished in the APAP group. Histological results confirmed the hepatotoxicity induced by APAP. However, UMB (more effective at 60 and 120 mg/kg) lessened APAP-induced hepatic injuries, which is comparable with NAC effects.

Conclusion and implications: The findings of this study provided evidence that UMB ameliorates liver injury induced by APAP through its antioxidant and anti-inflammatory effects.


Keywords


Acetaminophen; Hepatotoxicity; Inflammation; Oxidative stress; Umbelliferone.

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References


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