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Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats.
Pharm Biol 2017; 55(1):1809-1816PB

Abstract

CONTEXT

Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects.

OBJECTIVE

The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated.

MATERIALS AND METHODS

Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined.

RESULTS

APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6 ± 0.21 nmol/mg) as well as a decrease in the contents of TAC (1.75 ± 0.14 μmol/g), GSH (1.9 ± 0.22 μmol/g) and GST) 3.2 ± 0.28 U/mg). RA treatment decreased MDA (4.32 ± 0.35 nmol/mg) but increased the contents of TAC (3.51 ± 0.34 μmol/g), GSH (3.42 ± 0.16 μmol/g) and GST (5.71 ± 0.71 μmol/g) in APAP group. RA 100 mg/kg decreased ALT (91.5 ± 1.5 U/L), AST (169 ± 8.8 U/L) and CYP450 (3 ± 0.2 nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group.

DISCUSSION AND CONCLUSIONS

This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity.

Authors+Show Affiliations

a Department of Biology , School of Basic Sciences, Bu-Ali Sina University , Hamedan , Iran.a Department of Biology , School of Basic Sciences, Bu-Ali Sina University , Hamedan , Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28545313

Citation

Hasanein, Parisa, and Maryam Sharifi. "Effects of Rosmarinic Acid On Acetaminophen-induced Hepatotoxicity in Male Wistar Rats." Pharmaceutical Biology, vol. 55, no. 1, 2017, pp. 1809-1816.
Hasanein P, Sharifi M. Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats. Pharm Biol. 2017;55(1):1809-1816.
Hasanein, P., & Sharifi, M. (2017). Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats. Pharmaceutical Biology, 55(1), pp. 1809-1816. doi:10.1080/13880209.2017.1331248.
Hasanein P, Sharifi M. Effects of Rosmarinic Acid On Acetaminophen-induced Hepatotoxicity in Male Wistar Rats. Pharm Biol. 2017;55(1):1809-1816. PubMed PMID: 28545313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats. AU - Hasanein,Parisa, AU - Sharifi,Maryam, PY - 2017/5/27/entrez PY - 2017/5/27/pubmed PY - 2018/4/3/medline KW - Hepatoprotective KW - antioxidant KW - lipid peroxidation KW - liver KW - oxidative stress KW - paracetamol SP - 1809 EP - 1816 JF - Pharmaceutical biology JO - Pharm Biol VL - 55 IS - 1 N2 - CONTEXT: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. OBJECTIVE: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. MATERIALS AND METHODS: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined. RESULTS: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6 ± 0.21 nmol/mg) as well as a decrease in the contents of TAC (1.75 ± 0.14 μmol/g), GSH (1.9 ± 0.22 μmol/g) and GST) 3.2 ± 0.28 U/mg). RA treatment decreased MDA (4.32 ± 0.35 nmol/mg) but increased the contents of TAC (3.51 ± 0.34 μmol/g), GSH (3.42 ± 0.16 μmol/g) and GST (5.71 ± 0.71 μmol/g) in APAP group. RA 100 mg/kg decreased ALT (91.5 ± 1.5 U/L), AST (169 ± 8.8 U/L) and CYP450 (3 ± 0.2 nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group. DISCUSSION AND CONCLUSIONS: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity. SN - 1744-5116 UR - https://www.unboundmedicine.com/medline/citation/28545313/Effects_of_rosmarinic_acid_on_acetaminophen_induced_hepatotoxicity_in_male_Wistar_rats_ L2 - http://www.tandfonline.com/doi/full/10.1080/13880209.2017.1331248 DB - PRIME DP - Unbound Medicine ER -