Silymarin prevents acetaminophen-induced hepatotoxicity in mice

Abstract

Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination. SLM treatment significantly reduced superoxide production, as indicated by lower GSSG content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK activation and direct measurement of mitochondrial superoxide production in vitro. SLM did not affect the APAP-induced decrease in CYP2E1 activity and expression during the first 12 hrs. Neutrophil infiltration and enhanced expression of inflammatory markers were first detected at T12 in both groups. Inflammation progressed in the APAP group at T24 but became attenuated in SLM-treated animals. Histological examination suggests that necrosis the dominant cell death pathway in APAP intoxication, which is partially preventable by SLM pretreatment. We demonstrate that SLM significantly protects against APAP-induced liver damage through the scavenger activity of SLM and the reduction of superoxide and peroxynitrite content. Neutrophil-induced damage is probably secondary to necrosis development.

Effects of phenolic compounds from aqueous extract of Trifolium repens against acetaminophen‐induced hepatotoxicity in mice

“…TR extract and silymarin showed similar resistance to toxicity induced by acetaminophen which indicates that the valuable compounds present in TR extract possess similar properties as shown by silymarin. The present study is in accordance with Papackova et al (), which support PS group results. They showed that induced hepatotoxicity injury can be reduced by silymarin.…”

Protection efficiency of red radish seeds and roots against paracetamol mediated hepatotoxicity in rats

“…In such case, reactive oxygen species, nitric oxide, peroxinitrite derivatives, lipid peroxidation and protein nitrates have roles in hepatotoxicity (24). Several studies demonstrated that paracetamol mediated oxidative damage and hepatotoxicity in rats and mice, resulting in enhancement of the liver parameters (25)(26)(27). In the present study oral administration of a single dose of 2 g paracetamol/kg body wt on the 22nd day induced oxidative stress and toxicity in the liver.…”

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

“…Silybin interferes in oxidative stress, accumulation of fat in liver, and insulin resistance (Federico, Dallio, & Loguercio, ; Marin et al, ). It improves functional liver tests (Aller et al, ) and leads to a reduction in hepatotoxicity induced by high doses of acetaminophen and can diminish oxidative stress in mice (Brandon‐Warner et al, ; Papackova et al, ). In patients with chronic hepatitis C, silymarin has antiviral (Lani et al, ; Polyak, Ferenci, & Pawlotsky, ) and hepatoprotective role (Polyak et al, ).…”

“…and leads to a reduction in hepatotoxicity induced by high doses of acetaminophen and can diminish oxidative stress in mice (Brandon-Warner et al, 2012;Papackova et al, 2018). In patients with chronic hepatitis C, silymarin has antiviral (Lani et al, 2015;Polyak, Ferenci, & Pawlotsky, 2013) and hepatoprotective role (Polyak et al, 2013).…”