Curcumin Attenuates D-Galactosamine/Lipopolysaccharide–Induced Liver Injury and Mitochondrial Dysfunction in Mice

Abstract

Curcumin, a naturally occurring antioxidant, has various beneficial effects in the treatment of human diseases. However, little information regarding the protection it provides against acute liver injury is available. The present study investigated the protective effects of curcumin against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. A total of 40 male Kunming mice were randomly assigned to 5 groups: 1) mice administered saline vehicle injection (control), 2) mice administered 200 mg/kg body weight (BW) curcumin by i.p. injection (CUR), 3) mice administered D-GalN/LPS (700 mg and 5 μg/kg BW) via i.p. injection (GL), 4) mice administered 200 mg/kg BW curcumin i.p. 1 h before D-GalN/LPS injection (CUR-GL), and 5) mice administered 200 mg/kg BW curcumin i.p. 1 h after D-GalN/LPS injection (GL-CUR). Twenty h after D-GalN/LPS injection, serum alanine aminotransferase activities were 18.5% and 13.5% lower (P < 0.05) and aspartate aminotransferase (AST) activities were 26.6% and 9.6% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. The CUR-GL and GL-CUR groups had 64.4% and 15.0% higher (P < 0.05) mitochondrial membrane potentials, respectively, and the CUR-GL group had a 44.7% lower reactive oxygen species concentration than the GL group (P < 0.05). Mitochondrial manganese superoxide dismutase activities were 111% and 77.9% higher (P < 0.05) and the percentages of necrotic cells were 47.0% and 32.4% lower (P < 0.05) in the CUR-GL and GL-CUR groups, respectively, than in the GL group. Liver mRNA levels of sirtuin 1 (Sirt1) were 56.4% lower (P < 0.05) in the CUR-GL group than in the GL group. Moreover, compared with the GL-CUR group, the CUR-GL group had an 18.7% lower serum AST activity, a 31.7% lower mitochondrial malondialdehyde concentration, a 36.0% lower hepatic reactive oxygen species concentration, and a 43.0% higher mitochondrial membrane potential. These results suggested that curcumin protects against D-GalN/LPS-induced liver damage by the enhancing antioxidant defense system, attenuating mitochondrial dysfunction and inhibiting apoptosis. This was especially true for curcumin pretreatment, which highlighted its promise as a preventive treatment for acute liver injury in clinical settings.

Hepatoprotective Effect of Curcumin and Capsaicin against Lipopolysaccharide Induced Liver Damage in Mice

“…showed significant detoxification, thereby reduced the leakage of SGOT, SGPT, ALP and total bilirubin from the hepatocytes indicating the inhibition of LPS induced toxicity in mice. These results are in agreement with the earlier reports of Zhanq et al 34 (2014) and Abdel et al 33 (2012). Where, intraperitoneal administration of curcumin (200 mg/kg b.w) and capsaicin (15,150 and 1500 µg/kg b.w) significantly reduced the LPS induced liver toxicity respectively.…”

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and/ or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

“…Previous study documented that silymarin possesses substantial protective effect against DNA damage and apoptosis induced by the environmental pollutant benzo (a) pyrene (Perumal et al 2012). Also, the effectiveness of vitamin E in quenching free radicals and functioning as a membrane stabilizer was also documented (Zhang et al 2014). It was shown that liver 8-OHdG levels increased significantly in rats intoxicated with CCl4 as compared to the control rats.…”

Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

“…Fulminant hepatic failure can be caused by different agents such as alcohols, chemicals, and viruses [2][3][4]. LPS and GalN are the most common agents that cause hepatic injury [5,6]. The model was widely used to explore the pathogenesis of fulminant hepatitis and develop novel liver-protective reagents [7].…”