Hepatoprotective activity of Psidium guajava Linn. leaf extract

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.     

Dimerumic acid as an antioxidant of the mold, Monascus anka

We previously reported that the mold Monascus anka, traditionally used for fermentation of food, showed antioxidant and hepatoprotective actions against chemically induced liver injuries. In the present study, the antioxidant component of M. anka was isolated and identified. The antioxidant was elucidated to be dimerumic acid. DPPH (1,1-diphenyl-2-picrylhydrazyl) radical was significantly scavenged by the antioxidant whereas hydroxyl radical and superoxide anion were moderately scavenged. When the antioxidant (12 mg/kg) was given to mice prior to carbon tetrachloride (CCl(4), 20 microl/kg, ip) treatment, the CCl(4)-induced liver toxicity in mice seen in an elevation of serum aspartate aminotransferase and alanine aminotransferase activities was depressed, suggesting the hepatoprotective action of the antioxidant. The liver microsomal glutathione S-transferase activity, which is known to be activated by oxidative stress or active metabolites, was increased by CCl(4) treatment and the increase was also depressed by pretreatment with the mold antioxidant. Thus these data confirmed that the dimerumic acid isolated from M. anka is the potential antioxidant and protective against CCl(4)-induced liver injury.     

Exopolysaccharide-peptide complex from oyster mushroom (Pleurotus ostreatus) protects against hepatotoxicity in rats

Liver damage involves oxidative stress and a progression from chronic hepatitis to hepatocellular carcinoma (HCC). The increased incidence of liver disease in Egypt and other countries in the last decade, coupled with poor prognosis, justify the critical need to introduce alternative chemopreventive agents that may protect against liver damage. The aim of this study was to evaluate the efficacy of exopolysaccharide-peptide (PSP) complex extracted from Pleurotus ostreatus as a hepatoprotective agent against diethylnitrosamine (DEN)/carbon tetrachloride (CCL₄)-induced hepatocellular damage in rats. The levels of liver injury markers (ALT, AST and ALP) were substantially increased following DEN/CCl₄ treatment. DEN/CCl₄ - induced oxidative stress was confirmed by elevated levels of lipid peroxidation and decreased levels of superoxide dismutase, glutathione-S-transferase, and reduced glutathione. PSP reversed these alterations in the liver and serum, and provided protection evidenced by reversal of histopathological changes in the liver. The present study demonstrated that PSP extract from P. ostreatus exhibited hepatoprotective and antioxidant effects against DEN/CCl₄-induced hepatocellular damage in rats. Given the high prevalence of HCV-related liver damage in Egypt, our results suggest further clinical evaluation of P. ostreatus extracts and their potential hepatoprotective effects in patients with liver disease.     

Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats

Methanol and aqueous leaf extracts of L. hirta demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats. The parameters studied were serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum markers and decrease in total protein level reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with methanol and aqueous leaf extracts showed significant decrease in the levels of serum markers and increase in total protein indicating the protection of hepatic cells. The results revealed that methanol leaf extract followed by aqueous extract of L. hirta could afford significant protection against CCl4 induced hepatocellular injury.     

Antioxidant and hepatoprotective activities of low molecular weight sulfated polysaccharide from Laminaria japonica

A low molecular weight sulfated polysaccharide (LMWF) was prepared from Laminaria japonica by mild acid hydrolysis. The antioxidant activity of LMWF in vitro was studied using three kinds of oxygen free radical systems. LMWF had effective scavenging abilities on superoxide radical, hydroxyl radical and hypochlorous acid directly in vitro. The hepatoprotective effect of LMWF was studied using two acute liver injury mice models induced by carbon tetrachloride (CCl₄) and D-galactosamine (D-GalN). Addition of LMWF significantly lowered the content of serum malonaldehyde and markedly increased the activities of superoxide dismutase and glutathione peroxidase, compared with the model groups in both kinds of liver injury mice. Moreover, administration of LMWF significantly inhibited the elevation of glutamate pyruvate transaminase induced by CCl₄ and D-GalN in mice. The results suggest that the antioxidant activity of LMWF plays an important role in its hepatoprotective effect in the liver injury mice induced by CCl₄ and D-GalN.     

虫草素对四氯化碳所致小鼠急性肝损伤的保护作用

本文探究蛹虫草活性成分虫草素对四氯化碳（CCl₄）造成的小鼠急性肝损伤的保护作用及其分子机制。首先建立四氯化碳致小鼠急性肝损伤的动物模型,通过检测血清生化指标、肝功指标的变化及HE染色观察组织切片病理的病变情况,评价虫草素的保肝效果,进一步通过Western blot检测虫草素能否通过激活Nrf-2/Keap1信号通路及其下游抗氧化因子（HO-1、NQO-1）的表达来提高机体抗氧化损伤能力以及抑制炎症因子（TNFα、TNFβ、IL-6、IL-10）的表达。对比模型组结果显示,虫草素能极显著降低（P<0.01）小鼠血清中ALT、AST及肝脏中MDA水平,并能极显著提高肝脏中SOD水平（P<0.01）;HE染色结果显示虫草素能有效降低改善受损肝组织中的炎细胞浸润及纤维组织增生;Western blot结果表明虫草素能够通过激活Nrf-2信号通路,促进下游抗氧化因子及抗炎因子的表达,从而降低炎症反应。虫草素对CCl₄致小鼠急性肝损伤具有一定的保护作用,其机制与Nrf-2信号通路相关,实验结果为后续蛹虫草及虫草素的开发应用奠定基础。     

Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4-induced liver damage

We investigated hepatoprotective activity and antioxidant effect of the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene that purified from Morus bombycis Koidzumi roots against CCl4-induced liver damage in rats. The 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene displayed dose-dependent superoxide radical scavenging activity (IC50 = 430.2 microg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. The increase in aspartate aminotransferase (AST) activities in serum associated with carbon tetrachloride (CCl4)-induced liver injury was inhibited by 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene and at a dose of 400 - 600 mg/kg samples had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3'-di(beta-d-glucopyranosyloxy)-trans-stilbene decreased cell ballooning in response to CCl4 treatment. These results demonstrate that the 2,5-dihydroxy-4,3'-di(beta-D-glucopyranosyloxy)-trans-stilbene is a potent antioxidant with a liver protective action against CCl4-induced hepatotoxicity.     

The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats

Coumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl₄) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague–Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl₄, when compared to control values. Similarly, administration of CCl₄ increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg⁻¹, orally) and scoparone (35 mg kg⁻¹, orally) significantly prevented CCl₄-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg⁻¹) and coumarin (30 mg kg⁻¹) had no effect against CCl₄-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress.     

S-allyl cysteine prevents CCl(4)-induced acute liver injury in rats

Aged garlic extract (AGE) possesses multiple biological activities. We evaluated the protective effect of S-allyl cysteine (SAC), one of the organosulfur compounds of AGE, against carbon tetrachloride (CCl₄)-induced acute liver injury in rats. SAC was administrated intraperitoneally (50-200 mg/kg). SAC significantly suppressed the increases of plasma ALT and LDH levels. SAC also attenuated histological liver damage. CCl₄ administration induced lipid peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4-hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases. The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative stress biomarker, was closely correlated with the amount of liver damage. These results suggest that SAC decreased CCl₄-induced liver injury by attenuation of oxidative stress, and may be a better therapeutic tool for chronic liver disease.     

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.     

Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice

Oxidative stress has been recognized as a critical pathogenetic mechanism for the initiation and the progression of hepatic injury in a variety of liver disorders. Antioxidants, including many natural compounds or extracts, have been used to cope with liver disorders. The present study was designed to investigate the hepatoprotective effects of cassia seed ethanol extract (CSE) in carbon tetrachloride (CCl(4))-induced liver injury in mice. The animals were pre-treated with different doses of CSE (0.5, 1.0, 2.0 g/kg body weight) or distilled water for 5 days, then were injected intraperitoneally with CCl(4) (0.1% in corn oil, v/v, 20 ml/kg body weight), and sacrificed at 16 hours after CCl(4) exposure. The serum aminotransferase activities, histopathological changes, hepatic and mitochondrial antioxidant indexes, and cytochrome P450 2E1 (CYP2E1) activities were examined. Consistent with previous studies, acute CCl(4) administration caused great lesion to the liver, shown by the elevation of the serum aminotransferase activities, mitochondria membrane permeability transition (MPT), and the ballooning degeneration of hepatocytes. However, these adverse effects were all significantly inhibited by CSE pretreatment. CCl(4)-induced decrease of the CYP2E1 activity was dose-dependently inhibited by CSE pretreatment. Furthermore, CSE dramatically decreased the hepatic and mitochondrial malondialdehyde (MDA) levels, increased the hepatic and mitochondrial glutathione (GSH) levels, and restored the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione S-transferase (GST). These results suggested that CSE could protect mice against CCl(4)-induced liver injury via enhancement of the antioxidant capacity.     

Hepatoprotective,Immunomodulatory, and Anti-inflammatory Activities of Selenocystine in Experimental Liver Injury of Rats

The study was evaluated to investigate the efficacy of selenocystine (CysSeSeCys), a well-known organoselenium compound, on the prevention of carbon tetrachloride (CCl₄)-induced acute hepatic injury in Wistar rats. Forty healthy male Wistar rats were utilized in this study. Acute hepatotoxicity was induced by CCl₄ intoxication in rats. Serum biological analysis, oxidative stress, immune parameters, and gene expression of COX-2 and CYP2E1 were carried out. Pretreatment of CysSeSeCys prior to CCl₄ administration significantly prevented an increase in serum hepatic enzymatic activities. In addition, pretreatment of CysSeSeCys significantly prevented the formation of ROS, MDA, depletion of glutathione, and alteration of antioxidant enzyme activities in the liver of CCl₄-intoxicated rats. This study also revealed that pretreatment with CysSeSeCys normalized the levels of interleukin 6 and10, IgG, and CD4 cell count. Pretreatment of CysSeSeCys significantly reversed COX-2 inflammatory response and the upregulation of CYP2E1 expression as well. Histopathological changes induced by CCl₄ were also significantly attenuated by CysSeSeCys pretreatment. CysSeSeCys has a potent hepatoprotective effect on CCl₄-induced liver injury in rats through its antioxidative, immunomodulatory and anti-inflammatory activity.     

Protective effects of Ephedra pachyclada extract on mouse models of carbon tetrachloride- induced chronic and acute liver failure

Inflammation and oxidation are two important factors in the pathogenesis of liver. Ephedra pachyclada (EP) is a traditional medical herb that has anti-inflammatory and anti-oxidant activities. During this study, anti-oxidant activities of the EP extract was measured in vitro by 2,2′- diphenyl-1-picrylhydrazyl (DPPH) and β-Carotene bleaching assays. Then, we examined possible in vivo hepatoprotective effects of EP extract on mouse models of carbon tetrachloride (CCl₄)-induced chronic and acute liver failure. To produce mouse models of chronic and acute liver injuries, male SW1 mice were interaperitoneally injected with 1 ml/kg body weight (bw) CCl₄ biweekly for 42 days and a single dose of 2 ml/kg bw, respectively. In the experimental groups, mouse models were treated with low (140 mg/kg bw) and high (1400 mg/kg bw) doses of the EP extract. Olive oil and water treated mice were considered as controls during model derivation and EP extract treatment respectively. The results showed the antioxidant activity of EP extract and a significant reduction of all parameters of CCl₄-induced liver injury such as relative liver weight, necrosis, fibrosis, inflammation, and serum aspartate transaminase (AST) and alanine aminotransferase (ALT) in mouse models of acute and chronic liver injury treated with EP extract. Therefore, EP induces its hepatoprotective effects probably by suppressing oxidative stress and inhibit inflammation in the liver and is able to protect the liver against CCl₄-induced acute and chronic injuries.     

Hepatoprotective activity of Luffa acutangula against CCl4 and rifampicin induced liver toxicity in rats: a biochemical and histopathological evaluation

Hepatoprotective activity of hydroalcoholic extract of Luffa acutangula (HAELA) against carbon tetrachloride (CCl4) and rifampicin-induced hepatotoxicity in rats was evaluated and probable mechanism(s) of action has been suggested. Administration of standard drug- silymarin and HAELA showed significant hepatoprotection against CCl4 and rifampicin induced hepatotoxicity in rats. Hepatoprotective activity of HAELA was due to the decreased levels of serum marker enzymes viz., (AST, ALT, ALP and LDH) and increased total protein including the improvement in histoarchitecture of liver cells of the treated groups as compared to the control group. HAELA also showed significant decrease in malondialdehyde (MDA) formation, increased activity of non-enzymatic intracellular antioxidant, glutathione and enzymatic antioxidants, catalase and superoxide dismutase. Results of this study demonstrated that endogenous antioxidants and inhibition of lipid peroxidation of membrane contribute to hepatoprotective activity of HAELA.     

S-allyl cysteine prevents CCl4-induced acute liver injury in rats

Aged garlic extract (AGE) possesses multiple biological activities. We evaluated the protective effect of S-allyl cysteine (SAC), one of the organosulfur compounds of AGE, against carbon tetrachloride (CCl₄)-induced acute liver injury in rats. SAC was administrated intraperitoneally (50–200 mg/kg). SAC significantly suppressed the increases of plasma ALT and LDH levels. SAC also attenuated histological liver damage. CCl₄ administration induced lipid peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4-hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases. The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative stress biomarker, was closely correlated with the amount of liver damage. These results suggest that SAC decreased CCl₄-induced liver injury by attenuation of oxidative stress, and may be a better therapeutic tool for chronic liver disease.     

Hepatoprotective effect of Hibiscus hispidissimus Griffith, ethanolic extract in paracetamol and CCl4 induced hepatotoxicity in Wistar rats

Hibiscus hispidissimus Griff. is used in tribal medicine of Kerala, the southern most state of India, to treat liver diseases. In the present study, the effect of the ethanolic extract of Hibiscus hispidissimus whole plant on paracetamol (PCM)-induced and carbon tetrachloride (CCl4)-induced liver damage in healthy Wistar albino rats was studied. The results showed that significant hepatoprotective effects were obtained against liver damage induced by PCM and CCl4 as evidenced by decreased levels of serum enzymes, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SAKP), serum bilirubin (SB) and an almost normal histological architecture of the liver of the treated groups compared to the toxin controls. The extract also showed significant antilipid peroxidant effects in vitro, besides exhibiting significant activity in quenching 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, indicating its potent antioxidant effects.     

铁棍山药多糖对四氯化碳诱导的急性小鼠肝损伤的保护作用

为了研究铁棍山药(D.oppositacv.Tiegun)多糖对四氯化碳诱导的小鼠急性肝损伤的保护作用,取72只昆明小鼠随机分为对照组,四氯化碳(CCl4)模型组,阳性对照(联苯双酯)组,铁棍山药多糖低、中、高剂量组,每组12只,灌胃处理后使用CCl4制备急性肝损伤小鼠模型,观察各组形态学变化,同时测定生化指标。实验结果显示,经铁棍山药多糖处理的小鼠的肝损伤程度明显轻于模型组,铁棍山药多糖能降低小鼠血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)含量,提高超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性,降低丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)的含量。本研究结果表明,铁棍山药多糖对CCl4所诱导的小鼠肝损伤起到一定的保护作用。     

Hyaluronic acid and chondroitin-4-sulphate treatment reduces damage in carbon tetrachloride-induced acute rat liver injury

Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment.     

Identification of protein kinase C inhibitory activity associated with a polypeptide isolated from a phage display system with homology to PCM-1, the pericentriolar material-1 protein

L-arginine may aid in the liver detoxification and may benefit in the treatment of liver disorders such as liver injury. The present study was to investigate the possible protective and curative effects of L-arginine on carbon tetrachloride (CCl(4)) induced hepatotoxicity. Mice received a single dose of CCl(4). L-arginine treatment was given for 6 days prior or post to CCl(4) injection. CCl(4)-intoxication caused marked liver cell necrosis with inflammatory and apoptotic lesions. L-arginine treatment reduced hepatic necrosis and inflammation. CCl(4)-intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH level and inhibited the activities of antioxidant enzymes. Pre-treatment and post-treatment with L-arginine decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results suggest that L-arginine administration has hepatoprotective and hepatocurative effects against CCl(4) induced hepatotoxicity in mice.     

Serum thioredoxin reductase levels increase in response to chemically induced acute liver injury

Background

Mammalian thioredoxin reductases (TrxR) are selenoproteins with important roles in antioxidant defense and redox regulation, principally linked to functions of their main substrates thioredoxins (Trx). All major forms of TrxR are intracellular while levels in serum are typically very low.

Methods

Serum TrxR levels were determined with immunoblotting using antibodies against mouse TrxR1 and total enzyme activity measurements were performed, with serum and tissue samples from mouse models of liver injury, as triggered by either thioacetamide (TAA) or carbon tetrachloride (CCl₄).

Results

TrxR levels in serum increased upon treatment and correlated closely with those of alanine aminotransferase (ALT), an often used serum biomarker for liver damage. In contrast, Trx1, glutathione reductase, superoxide dismutase or selenium-containing glutathione peroxidase levels in serum displayed much lower increases than TrxR or ALT.

Conclusions

Serum TrxR levels are robustly elevated in mouse models of chemically induced liver injury.

General significance

The exaggerated TrxR release to serum upon liver injury may reflect more complex events than a mere passive release of hepatic enzymes to the extracellular milieu. It can also not be disregarded that enzymatically active TrxR in serum could have yet unidentified physiological functions.