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Protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity
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
Correspondence Address:
Ayman M Mahmoud
Department of Zoology, Division of Physiology, Faculty of Science, Beni-Suef University, Salah Salim St., 62514, Beni-Suef
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0973-1296.185765
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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. |
