Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats

Abstract

This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.

Figure 1

Serum parameters of rats of all groups untreated, treated with APAP (3 g/kg, orally), and pretreated with SLM (200 mg/kg) of ALT (a), AST (b), ALP (c), γ-GT (d), and GLU (e) were determined 12 h after APAP intoxication. Results represent mean ± SEM of 12 rats per group. ^* P < 0.05 N + APAP versus N, ^** P < 0.01 N + SLM + APAP versus N + APAP, ^* P < 0.05 SHR + APAP versus SHR, ^** P < 0.05 SHR + SLM + APAP versus SHR + APAP, ^# P < 0.05 N versus SHR, and ^## P < 0.05 N + APAP versus SHR + APAP.

Figure 2

Serum parameters of rats of all groups untreated, treated with APAP (3 g/kg, orally), and pretreated with SLM (200 mg/kg) of MPO activity (a) and NO production (b) were determined 12 h after APAP intoxication. Results represent mean ± SEM of 12 rats per group. ^* P < 0.05 N + APAP versus N, ^** P < 0.05 N + SLM + APAP versus N + APAP, ^* P < 0.05 SHR + APAP versus SHR, and ^** P < 0.05 SHR + SLM + APAP versus SHR + APAP.

Figure 3

Histopathology of livers 12 hours after APAP injection. The livers were collected 12 hours from all groups after APAP administration (3 g/kg). Panels (a) and (b): N and SHR group that received only vehicle, respectively, (c) and (d): N and SHR group that received APAP, respectively. (e) and (f): N and SHR group pretreated with standard drug (SLM, 200 mg/kg per 7 days). Arrows indicate leukocyte infiltration. Sections were stained with H&E (magnification, ×40).