Protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity

Nouf Al-Rasheed; Laila Faddah; Nawal Al-Rasheed; Yieldez A Bassiouni; Iman H Hasan; Ayman M Mahmoud; Raeesa A Mohamad; Hazar I Yacoub

Articles

Abstract

Pharmacognosy Magazine,2016,12,46s,s337-s345.

DOI:10.4103/0973-1296.185765

Published:May 2016

Type:Original Article

Authors:

Author(s) affiliations:

Nouf Al-Rasheed¹, Laila Faddah¹, Nawal Al-Rasheed², Yieldez A Bassiouni³, Iman H Hasan¹, Ayman M Mahmoud⁴, Raeesa A Mohamad⁵, Hazar I Yacoub¹
¹ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
² Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
³ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
⁴ Department of Zoology, Division of Physiology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
⁵ Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Abstract:

Objective: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl₄)-induced injury. Materials and Methods: Hepatotoxicity was induced by a single dose of CCl₄ (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/kg) and/or ME (20 mg/kg) for 21 days. Results: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase-3 activity were significantly attenuated in SIL treated CCl₄-intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl₄-intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. Conclusions: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl₄-induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies.