Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species

Mostafa M El-Shafey; Gamil M Abd-Allah; Ahmed M Mohamadin; Gamaleldin I Harisa; Amr D Mariee

doi:10.1016/j.pathophys.2014.12.002

Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species

Pathophysiology. 2015 Mar;22(1):49-55. doi: 10.1016/j.pathophys.2014.12.002. Epub 2014 Dec 15.

Authors

Mostafa M El-Shafey¹, Gamil M Abd-Allah¹, Ahmed M Mohamadin², Gamaleldin I Harisa³, Amr D Mariee⁴

Affiliations

¹ Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
² Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt; Department of Chemistry for Health Sciences, Deanery of Academic Services, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia.
³ Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt; Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁴ Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt. Electronic address: amrmariee@yahoo.co.uk.

PMID: 25547049
DOI: 10.1016/j.pathophys.2014.12.002

Abstract

High or toxic doses of acetaminophen (APAP), a mild analgesic and antipyretic drug, can cause life-threatening hepatic and renal dysfunction. This study is designed to investigate the potential protective role of quercetin to attenuate the hepatorenal toxicity induced by a high single oral dose (3g/kg) of APAP in rats. Three main groups of Sprague-Dawley rats were used: quercetin, APAP and quercetin plus APAP-receiving animals. Corresponding control animals were also used. Interestingly, oral supplementation of quercetin (15mg/kg/day) prior to APAP intoxication dramatically reduced APAP-induced hepatorenal toxicity as evidenced by measuring serum lipid profile, total protein, urea, creatinine, ALT, AST, ALP, G-GT and liver tissue content of TC and TG. Quercetin treatment markedly prevented the generation of TBARS and PCC with substantial improvement in terms of GSH and activities of antioxidant enzymes in both liver and kidney homogenates. The relationship between quercetin and NO levels which is still a matter of debate, was also investigated. NO levels in serum, liver and kidney tissues were significantly inhibited in quercetin pre-treated animals. Furthermore, quercetin administration significantly inhibited the reduction of liver and kidney contents of ATP parcels associated with this hepatorenal toxicity. These results suggest that the protective role of quercetin in the prevention of APAP-induced hepatorenal toxicity in rats was associated with the decrease of oxidative and nitrosative stress in hepatic and renal tissues as well as its capacity to improve the mitochondrial energy production. However, clinical studies are warranted to investigate such an effect in human subjects.

Keywords: Acetaminophen; Hepatorenal; Nitric oxide; Quercetin; Rat.