Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents

Abstract

The present study is aimed at investigating the effect of curcumin (CMN) in salvaging endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rodents. Hepatotoxicity was induced by administering lipopolysaccharide (LPS) in a single dose of 1 mg/kg intraperitoneally to the animals, which were being treated with CMN daily for 7 days. Liver enzymes serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin and total protein were estimated in serum. Oxidative stress in liver tissue homogenates was estimated by measuring thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content and superoxide dismutase (SOD) activity. Serum and tissue nitrite was estimated using Greiss reagent and served as an indicator of NO production. A separate set of experiments was performed to estimate the effect of CMN on cytokine levels in mouse serum after LPS challenge. LPS induced a marked hepatic dysfunction evident by rise in serum levels of ALT, AST, ALP and total bilirubin (P < 0.05). TBARS levels were significantly increased, whereas GSH and SOD levels decreased in the liver homogenates of LPS-challenged rats. CMN administration attenuated these effects of LPS successfully. Further CMN treatment also regressed various structural changes induced by LPS in the livers of rats and decreased the levels of tumour necrosis factor-alpha and interleukin-6 in mouse plasma. In conclusion, these findings suggest that CMN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO, oxygen free radicals and cytokines.

Fig. 1

Effect of different doses of curcumin (CMN) administration on serum and liver nitrite after lipopolysaccharide (LPS) challenge. Values are expressed as percentage response compared to control rats. ^aP< 0·05 compared to vehicle and saline-treated group. ^bP< 0·05 compared to vehicle and LPS-challenged rats.

Fig. 2

Effect of different doses of curcumin (CMN) administration on lipopolysaccharide (LPS)-induced lipid peroxidation (MDA), reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in liver homogenates. Values are expressed as percentage response compared to control rats. ^aP< 0·05 compared to vehicle and saline-treated group. ^bP< 0·05 compared to vehicle and LPS-challenged rats.

Fig. 3

(a) Haemotoxylin and eosin (H&E)-stained longitudinal section of liver of saline-treated rats (40×). (b) H&E-stained longitudinal section of liver of rats, 6 h after lipopolysaccharide (LPS) challenge (40×). (a). Kupffer cell hyperplasia (b) necrosis. (c) H&E-stained longitudinal section of liver of LPS-treated rats 6 h after LPS challenge (40×) (c). PMN infiltration (d) pyknotic nucleus. (d) H&E-stained longitudinal section of liver of curcumin-treated rats and 6 h after LPS challenge (40×).