Manganese Superoxide Dismutase Therapy in a Murine Hepatitis-Associated Injury

Abstract

We aim to test the hypothesis that Con A-induced hepatitis and cell death can be prevented by the administration of the MnSOD mimetic MnTBAP. Male C57 mice were divided into 3 groups, 1) pretreated with MnTBAP (30 mg/kg) for 2 days and then Concanavalin A (Con A) (15 mg/kg); 2) pretreated with saline for 2 days and then Con A (15 mg/kg); 3) was the control treated with saline for 3 days. Extensive hepatic necrosis, with a significant increase in apoptosis, lipid peroxidation and decreased MnSOD enzymatic activity was found in the hepatic tissue of Con A-treated mice with significantly attenuation of all factors by pretreatment with MnTBAP. MnTBAP protected hepatocytes from Con A-induced hepatic injury with less degree of liver inflammation—ConA + MnTBAP (2.1 ± 0.4) vs. Con A (2.6 ± 0.3)—and significantly less cell death (1.2 ± 0.3 vs. 2.7 ± 0.4, p = 0.03). MnSOD supplementation attenuated the oxidative-induced stress effects of Con A-induced injury and the protective effects of MnSOD supplementation against Con A-induced hepatitis could be through its anti-oxidative properties. Further evaluation of MnSOD manipulation could have the potential to prevent ongoing hepatic injury in hepatitis

The Effect of Black Raspberry Extracts on MnSOD Activity in Protection Against Concanavalin A Induced Liver Injury

“…The hepatocyte protection by BRB extracts preserving MnSOD in Con A challenged liver is supported by the following observations, 1) an increase in the intracellular steady-state production of H 2 O 2 by MnSOD can protect against tumor necrosis factor induced apoptosis 27 ; 2) overexpression of MnSOD inhibited IFN-γ-mediated ROS accumulation and rescued cells from necroptosis 28 ; 3) in our previous study, we have found that supplementation with a MnSOD mimic-MnTBAP-can also protect the hepatocytes from Con A induced hepatitis 29 ; 4) in the current in vitro data, supplementation with a MnSOD mimic-MnTBAP-can also protect the hepatocytes, while abolishing the MnSOD activity by KCN cannot protect the liver of animals pretreated with BRB.…”

“…16, 29 Briefly, a colorimetric assay is done by measuring the a water soluble formazan dye, which produced by the reaction between WST-1 and superoxide anion (O 2 − ). The rate of the reduction with O 2 − was linearly related to the xanthine oxidase activity and is inhibited by SOD.…”