Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats

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.

Natural Compounds Rosmarinic Acid and Carvacrol Counteract Aluminium-Induced Oxidative Stress

“…Rosmarinic acid has been shown to be neuroprotective, attenuating oxidative stress and neuronal cell death in vitro [25][26][27] and reducing inflammatory responses in experimental models of an ischemic stroke [18,28]. Rosmarinic acid treatment decreases MDA in rat liver [56], as well as in mice brain [57], kidney, and liver [57,58]. Carvacrol decreases the peroxidation of phospholipid liposomes in the presence of iron(III) and ascorbate [59], and inhibits low-density lipoprotein oxidation in a concentration dependent manner in an in vitro system using human aortic endothelial cells [60].…”

Rosmarinic acid attenuates hepatic steatosis by modulating ER stress and autophagy in oleic acid-induced HepG2 cells

“…36 Based on the abovementioned ndings, we investigated the role of RA in ameliorating NAFLD in context with its well-established in vivo and in vitro hepatoprotective effects in improving insulin sensitivity and dampening oxidative stress-mediated injuries. [37][38][39] In the process of identifying potent treatment options, exploration of molecular targets to combat NAFLD is also emerging along with other therapies such as dietary intervention. 40,41 Moreover, proper understanding of the various pathophysiological processes underlying NAFLD becomes unavoidable for its anticipated strategic remedial measures.…”

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“…Group II: rats received fresh beetroot juice 2 ml/rat/day via gastric gavage for a one month 18,32 ; the fresh beetroots were obtained from a local market. Group III: experimental group were rats received paracetamol 400 mg/kg/day of BW (Body Weight) for one month based on the previously identified toxic dose in-vivo 1,2,12 ; Paracetamol were purchased from (Sigma-Aldrich, USA). Group IV:…”

“…Kupffer cells, while tissue changes include; congestion of portal triad and central vein as a result of narrowing, inflammatory cell infiltrate 11,12 . Biochemical changes include several alterations in enzymes and inflammatory mediators.…”