Novel Use of Silymarin as Delayed Therapy for Acetaminophen-Induced Acute Hepatic Injury

Abstract

Aim: Recently, we have demonstrated that silymarin has a comparable pharmaceutical activity as Phyllanthus urinaria extract when used to rescue mice from acetaminophen-induced acute liver injury. In the present study, we further compared the therapeutic action of silymarin with N-acetyl cysteine (commonly used in clinical practice for emergency treatments) as a rescuer in mice after administering a lethal dose of acetaminophen for 24 h. Methods: Acute liver injury was induced in the treatment groups by intraperitoneally administered acetaminophen at a dose of 550 mg/kg body weight on day 1. The control group received an equal volume of physiological saline intraperitoneally. From day 2 to 4, the treatment groups received various doses of silymarin or N-acetyl cysteine orally once daily, while the control group and the acetaminophen group received an equal volume of water orally. The mortality rate was recorded in all groups. On day 5, all mice were sacrificed for examination. Results: Silymarin greatly improved the counteracting effects on mortality rate as compared to N-acetyl cysteine. Conclusion: Silymarin should be further considered as an antidote for patients with acetaminopheninduced acute hepatic injury and delayed treatment.

Hepatoprotective effect of fermented ginseng and its major constituent compound K in a rat model of paracetamol (acetaminophen)-induced liver injury

“…FG and FRG were orally administered once a day with gavage at the dose of 50 mg/kg [3] for 8 consecutive days. SIL was orally administered at 100 mg/kg [14] in the same way as FG and FRG. As a control group, 0.3% sodium carboxymethyl cellose sodium was administered.…”

“…Since the protective effect of compound K against tert ‐butyl hydroperoxide‐induced liver injury was reported,[4] FG, the artificially enriched compound K content by Lactobacillus fermentation, was expected to be effective for the prevention of APAP‐induced liver injury. Therefore, we have evaluated the protective effect of FG against APAP‐induced liver injury, together with fermented‐red‐ginseng (FRG) and silymarin extracts (SIL) prepared from Silybum marianum Gearth, the latter of which contain silybin, a well‐known hepatoprotective and antitoxidant agent [14,15]…”

“…Therefore, we have evaluated the protective effect of FG against APAPinduced liver injury, together with fermented-red-ginseng (FRG) and silymarin extracts (SIL) prepared from Silybum marianum Gearth, the latter of which contain silybin, a well-known hepatoprotective and antitoxidant agent. [14,15] There have been some reports on effectiveness of ginseng against liver injury caused by APAP, but the mechanism is unclear. [16,17] Using deoxyribonucleic acid (DNA) microarray analysis, we also investigated the alteration of gene expression in the livers of APAP-administered rats, which were compared with those of rats pretreated with FG before APAP administration.…”

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

“…SLM is composed of several flavonolignans isomers (65–80%) with small amounts of flavonoids and fatty acids (20–35%) and other polyphenolic compounds [ 9 – 11 ]. The main isolated and structural active component of SLM is silybin, comprising about 33% of total SLM weight, and is clinically used [ 12 , 13 ] as hepatoprotector to treat liver injuries [ 14 ]. Besides, other biological activities for SLM, such as hepatoprotective/hepatic regenerator, immunomodulator, anti-inflammatory, antioxidant, and antifibrotic activities were described [ 11 , 13 , 15 ].…”

Protective effects of natsumikan (Citrus natsudaidai) extract on acetaminophen-induced lethal hepatotoxicity in mice

“…It has been reported that some medicinal plants, such as Phyllanthus urinaria ,[1112] Dioscorea alata L,[13] and Acanthopanax koreanum [14] have protective effects with regard to APAP-induced acute liver failure. As these medicinal plants are known to have antioxidative properties, we hypothesized that natsumikan may also have a protective effect on APAP-induced hepatotoxicity.…”