Taurine supplementation reduces oxidative stress and protects the liver in an iron-overload murine model

Abstract

We previously demonstrated that iron overload induces liver damage by causing the formation of reactive oxygen species (ROS). Taurine is a potent free radical scavenger that attenuates the damage caused by excessive oxygen free radicals. Therefore, the aim of the present study was to investigate whether taurine could reduce the hepatotoxicity of iron overload with regard to ROS production. Mice were intraperitoneally injected with iron 5 days/week for 13 weeks to achieve iron overload. It was found that iron overload resulted in liver dysfunction, increased apoptosis and elevated oxidative stress. Taurine supplementation increased liver taurine levels by 40% and led to improved liver function, as well as a reduction in apoptosis, ROS formation and mitochondrial swelling and an attenuation in the loss of the mitochondrial membrane potential. Treatment with taurine mediated a reduction in oxidative stress in iron‑overloaded mice, attenuated liver lipid peroxidation, elevated antioxidant enzyme activities and maintained reduced glutathione levels. These results indicate that taurine reduces iron‑induced hepatic oxidative stress, preserves liver function and inhibits hepatocyte apoptosis. Therefore, taurine may be a potential therapeutic drug to reduce liver damage caused by iron overload.

Figure 1

Effect of taurine on hepatocyte apoptosis in iron-overloaded mice. TUNEL-positive cells were apoptotic. (A–D) Liver sections from the different treatment groups: (A) placebo + vehicle, (B) placebo + taurine, (C) iron + vehicle and (D) iron + taurine (magnification, ×400). (E) Quantitative analysis of hepatocyte apoptosis expressed as the percentage of TUNEL-positive nuclei among the hepatocytes. Data are presented as the mean ± standard error of the mean (n=12). ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. the placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group. TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.

Figure 2

Effect of taurine on the activities of the antioxidant enzymes and lipid peroxidation in mice injected with iron over a 13-week period. (A–C) Activity of (A) SOD, (B) catalase, (C) GSH-Px and (D) MDA content. Data are presented as the mean ± standard error of the mean (n=12). ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. the placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group. SOD, superoxide dismutase; GSH-Px, glutathione-peroxidase; MDA, malondialdehyde.

Figure 3

Effect of taurine on hepatic (A) GSH and (B) GSSG levels, (C) the redox ratio (GSH/GSSG) and (D) GSH+GSSG levels in mice injected with iron over a 13-week period. Data are presented as the mean ± standard error of the mean (n=12). ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. the placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group. GSH, glutathione; GSSG, glutathione disulfide.

Figure 4

Effects of taurine on hepatic intercellular reactive oxygen species generation in mice injected with iron over a 13-week period. Data are presented as the mean ± standard error of the mean (n=12). ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. the placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group. DCF, dichloro-dihydro-fluorescein.

Figure 5

Effect of taurine on hepatocyte mitochondrial swelling in mice injected with iron over a 13-week period. Data are presented as the mean ± standard error of the mean (n=12). (A) Ca²⁺-induced mitochondrial swelling in iron-overloaded mice, with or without taurine supplementation. (B) Quantitative analysis of mitochondrial swelling. ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. the placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group.

Figure 6

Effect of taurine on the mitochondrial membrane potential in mice injected with iron over a 13-week period. Data are presented as the mean ± standard error of the mean (n=12). ^aP>0.05 vs. the placebo + vehicle group; ^bP<0.01 vs. placebo + vehicle and placebo + taurine groups and ^cP<0.01 vs. the iron + vehicle group.