L-Gln and L-Ser suppress the D-galactosamine-induced IL-18 expression and hepatitis

d-Galactosamine (GalN) induces acute hepatitis in experimental animals and this hepatitis has been shown to be suppressed by preceding ingestion of amino acids such as Gly, l-Ser, and l-Gln. However, little is known about the mechanism of its action. The present study shows for the first time that IL-18 reduction is involved in the suppressive actions of l-Gln and l-Ser on GalN-induced hepatitis. Elevation of IL-18 mRNA expression in liver and its concentration in serum in GalN-treated rats were found to be suppressed by preceding ingestion of 10% l-Gln- or 10% l-Ser diets, and resulted in the attenuation of the increase in serum transaminase (ALT and AST) activities, indexes of hepatic injury. These results suggest that suppressive effects of some dietary amino acids on the GalN-induced hepatitis are mediated by IL-18 reduction.     

Effect of a sake concentrate on the epidermis of aged mice and confirmation of ethyl alpha-D-glucoside as its active component

Generations of Japanese have appreciated the positive effects that sake can have on skin conditions, and studies have shown that concentrated sake suppressed the epidermal barrier disruption caused by ultraviolet B (UVB) irradiation. We investigated the effect of a topical application of a sake concentrate on the murine epidermis and found that the intercellular lipid content in an aged epidermis was significantly increased. Furthermore, the topical application of ethyl alpha-D-glucoside (alpha-EG), a component of sake, brought about a similar improvement in the levels of intercellular lipids. Following on from this, we confirmed that alpha-EG also significantly increased the content of loricrin protein, an indicator of successful corneocyte differentiation, while reducing the number of corneocyte layers in the aged stratum corneum. These results confirmed alpha-EG as the primary active component of the sake concentrate that had a positive effect on the epidermis. alpha-EG increased the intercellular lipid content, accelerated the differentiation of corneocytes, and reduced the thickness, thus improving the functions of the stratum corneum.     

自噬抑制剂氯喹对急性酒精诱导小鼠肝损伤的影响

目的：探讨自噬抑制剂氯喹（CQ）对急性酒精诱导肝损伤的影响及其作用机制。方法：将雄性C57BL/6小鼠随机分为3组：正常对照组、酒精组、氯喹干预组（n=7）,其中酒精组按4.5 g/kg剂量给予33%（V/V）酒精灌胃。HE和油红O染色检测各组小鼠肝组织脂滴变化;检测肝组织甘油三酯（TG）含量变化;检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）活性;免疫荧光法检测微管相关蛋白轻链3（LC3）蛋白变化;Western blot法检测LC3蛋白和核蛋白P65表达的变化;ELISA法检测促炎因子TNF-α、IL-6的变化。结果：与对照组比较,酒精组脂滴形成、TG含量、血清AST和ALT活性明显增高。与对照组比较,酒精组LC3-Ⅱ蛋白表达明显增加;与酒精组比较,氯喹干预组使酒精诱导的LC3-Ⅱ蛋白表达增强进一步加剧,使酒精诱导的TG含量、血清AST和ALT活性进一步增高,同时增加了酒精诱导的p65入核及TNFα、IL-6释放。结论：急性酒精能引起小鼠肝脏脂肪变化及炎症,而自噬抑制剂氯喹抑制自噬进程,加剧酒精诱导的肝损伤,说明自噬在酒精诱导肝损伤中可能具有保护效应。     

Differential effects of dietary casein and soybean protein isolate on lipopolysaccharide-induced hepatitis in D-galactosamine-sensitized rats

Effects of dietary protein type on lipopolysaccharide (LPS)-induced hepatitis, as assessed by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, were investigated in D-galactosamine (GalN)-sensitized rats. The plasma ALT and AST activities in rats fed on 25% soybean protein isolate (SPI) diet were significantly suppressed to about 1/4 and 1/5 of the values in rats fed on 25% casein diet, respectively, 8 h after the injection of LPS + GalN. Although hepatic ALT and AST activities of normal rats were also lower in the SPI group than in the casein group, this could not explain the differences in plasma enzyme activities between the two groups. The hepatic glutathione concentration of normal rats was lower in the SPI group than in the casein group, but it was reversed in rats injected with drugs. The results suggest that SPI can protect animals from LPS + GalN-induced hepatitis, and that the hepatic glutathione level may participate in the effects of SPI.     

Effects of various kinds of dietary amino acids on the hepatotoxic action of D-galactosamine in rats

The protective effects of various kinds of dietary amino acids against the hepatotoxic action of D-galactosamine (GalN) were examined. Male Wistar rats fed with 20% casein diets containing 10% or 5% amino acid for one week were injected with GalN (800 mg/kg body weight), and the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, the hepatic glycogen concentration, and the serum glucose-level were examined 20 hours after the injection. In the groups with the 10% amino acid diets, activities of AST, ALT, and LDH in serum of 10% L-glutamine (Gln), 10% L-asparagine (Asn), and 10% L-serine (Ser) groups were significantly lower than those of the control group, and in the groups with the 5% amino acid diets, those activities of 5% L-histidine (His), 5% L-tyrosine (Tyr), 5% L-lysine (Lys), and 5% L-glycine (Gly) groups were also lower than those of the control group. The concentration of liver glycogen of 10% Gln-, 10% Asn-, and 10% Ser- groups and those levels of 5% His-, 5% Tyr-, 5% Lys-, and 5% Gly-groups were also significantly higher than that of the control group. As a result, it was found that some kinds of dietary amino acid such as L-Ser, L-Asn, L-His, L-Lys, L-Tyr, and L-Gly, in addition to L-Gln were effective to protect the rats from GalN-induced injury.     

Hepatoprotective effects of purple potato extract against D-galactosamine-induced liver injury in rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-alpha, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.     

Hepatoprotective Effects of Purple Potato Extract against D-Galactosamine-Induced Liver Injury in Rats

We investigated the hepatoprotective effect of purple potato extract (PPE) against D-galactosamine (GalN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then GalN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-α), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of GalN, but PPE inhibited GalN-induced alterations in serum TNF-α, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + GalN group were higher and lower respectively than those in the control group, and those in the PPE + GalN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2′-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects against GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats.     

柴芩承气汤对重症急性胰腺炎并发肝损伤大鼠的治疗作用及其机制

目的：研究柴芩承气汤（CQCQD）对重症急性胰腺炎（SAP）并发肝损伤大鼠的治疗作用及其机制。方法：72只SD大鼠随机分为3组（n=24）：假手术（sham）组,重症急性胰腺炎模型（SAP）组和柴芩承气汤治疗（CQCQD）组。去氧胆酸钠胰胆管逆行注射建立SAP大鼠模型,CQCQD组给予柴芩承气汤治疗,于造模后1 h、5 h、10 h观察各组不同时间点的胰腺、肝脏组织病理学变化,检测血清中淀粉酶（AMS）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性、白介素-6（IL-6）水平及胰腺、肝脏组织单核细胞趋化蛋白-1（MCP-1）和IL-6 mRNA的表达情况。结果：与sham组比较,SAP组血清AMS、ALT、AST活性及IL-6水平明显升高,胰腺、肝脏组织MCP-1及IL-6 mRNA表达升高（P<0.05）;与SAP组比较,CQCQD组血清AMS、ALT、AST活性及IL-6水平明显降低;胰腺和肝脏组织病理损伤减轻,胰腺、肝脏组织MCP-1及IL-6 mRNA表达明显减弱（P<0.05）。结论：MCP-1参与了SAP并发肝损伤的进展;柴芩承气汤能显著抑制胰腺、肝脏组织MCP-1的表达,减轻SAP时胰腺、肝脏组织病理损伤,对SAP并发肝损伤起到治疗作用。     

Rapid release of tissue enzymes into blood after blast exposure: potential use as biological dosimeters

Explosive blast results in multiple organ injury and polytrauma, the intensity of which varies with the nature of the exposure, orientation, environment and individual resilience. Blast overpressure alone may not precisely indicate the level of body or brain injury after blast exposure. Assessment of the extent of body injury after blast exposure is important, since polytrauma and systemic factors significantly contribute to blast-induced traumatic brain injury. We evaluated the activity of plasma enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase (CK) at different time points after blast exposure using a mouse model of single and repeated blast exposures to assess the severity of injury. Our data show that activities of all the enzymes in the plasma were significantly increased as early as 1 h after blast exposure. The elevated enzyme activity remained up to 6 h in an overpressure dose-dependent manner and returned close to normal levels at 24 h. Head-only blast exposure with body protection showed no increase in the enzyme activities suggesting that brain injury alone does not contribute to the systemic increase. In contrast to plasma increase, AST, ALT and LDH activity in the liver and CK in the skeletal muscle showed drastic decrease at 6 h after blast exposures. Histopathology showed mild necrosis at 6 h and severe necrosis at 24 h after blast exposures in liver and no changes in the skeletal muscle suggesting that the enzyme release from the tissue to plasma is probably triggered by transient cell membrane disruption from shockwave and not due to necrosis. Overpressure dependent transient release of tissue enzymes and elevation in the plasma after blast exposure suggest that elevated enzyme activities in the blood can be potentially used as a biological dosimeter to assess the severity of blast injury.     

Plasma kinetics and urine profile of ethyl glucosides after oral administration in the rat

In this in vivo study, the time course of plasma concentration and the urinary excretion of ethyl alpha-D-glucoside (alpha-EG) and ethyl beta-D-glucoside (beta-EG) were investigated in rats after a single oral dose of 4 mmol/kg body weight. Maximal plasma concentrations of both alpha-EG and beta-EG (EGs) reached approximately 3 mM at 1 h after oral administration and then decreased rapidly. Approximately 80% of EGs administered were excreted into the urine during the first 6 h. Within 24 h, cumulative urinary alpha-EG and beta-EG excretions were estimated to be 87.2+/-7.9% and 85.4+/-5.0%, respectively. Traces of both EGs were detected in plasma and urine 24 h after oral ingestion. The results of this study indicate that almost all of both EGs was rapidly absorbed into the blood stream and easily excreted into the urine after oral administration, and that a small amount of them remained in the rat body 24 h after administration.     

MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.     

Protective effect of aescin from the seeds of Aesculus hippocastanum on liver injury induced by endotoxin in mice

To investigate the effect and underlying mechanism of aescin on acute liver injury induced by endotoxin, liver injury was established by injecting lipopolysaccharide (LPS) in mice. Animals were assigned to seven groups: the control group and groups treated with LPS (40 mg/kg), aescin (3.6 mg/kg), LPS plus dexamethasone (4 mg/kg) and LPS plus aescin (0.9, 1.8 or 3.6 mg/kg). Hepatic histopathological changes were examined under a light microscope. Activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were determined. Levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO) and antioxidative parameters in liver homogenate were measured. Glucocorticoid receptor (GR), 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and 11 beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expressions in liver were determined by western blotting. Treatment with escin could inhibit immigration of inflammatory cells, alleviate the degree of necrosis, and decrease serum ALT and AST activities. Aescin also down-regulated levels of inflammation mediators (TNF-α, IL-1β and NO) and 11β-HSD2 expression in liver, up-regulated GR expression, enhanced endogenous antioxidative capacity, but have no obvious effect on 11β-HSD1 expression in liver. The findings suggest aescin has protective effects on endotoxin-induced liver injury, and the underlying mechanisms were associated with its anti-inflammatory effects, up-regulating GR expression, down-regulating 11β-HSD2 experssion, and antixoidation.     

Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway

Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway.     

Preventive effect of omega-3 fatty acids in a rat model of stress-induced liver injury

Omega-3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega-3 fatty acids related to acute cold-restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega-3 group, each rat was pretreated with omega-3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega-3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase-3. Results showed that pretreatment of stressed rats with omega-3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF-α. Also, they improved liver damage and suppressed hepatic caspase-3 expression. In conclusion, pretreatment of stressed rats with omega-3 fatty acids has ameliorated stress-induced liver damage due to their antioxidant, anti-inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.     

Laboratory assessment of hepatic injury in the woodchuck (Marmota monax)

Normal reference values for total serum protein, albumin, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (GGT), alkaline phosphatase (AP), and total bilirubin were established in 48 clinically healthy woodchucks. To validate the use of these biochemical tests in the woodchuck for assessment of liver injury, carbon tetrachloride was administered to produce hepatocellular necrosis and the common bile duct was surgically occluded to produce cholestasis. Biochemical tests were performed prior to experimental treatment and thereafter in surviving woodchucks for a period of 6 weeks. There were marked increases in the serum activities of AST, ALT, and SDH following carbon tetrachloride administration and all 3 enzymes appeared to be useful markers of acute hepatocellular injury. The predominate biochemical abnormalities in woodchucks with bile duct obstruction were hyperbilirubinemia, hypercholesterolemia and increased serum AP and GGT activities. The increase of GGT occurred earlier following bile duct obstruction and the magnitude of increase was greater than that of AP, suggesting that GGT would be the preferred serum enzyme test in the woodchuck for assessment of cholestatic liver injury.     

血管活性肠肽对脓毒性休克大鼠肝损伤的保护作用

采用盲肠结扎穿孔(cecal ligation and puncture,CLP)法制备脓毒性休克大鼠模型,探讨血管活性肠肽(vasoactive intestinal peptide,VIP)对脓毒性休克大鼠肝损伤的保护作用及其可能机制.将48只雄性SD大鼠随机分成4组:假手术组(SO,n=12)、CLP组(n=12)、VIP组(n=12)和生理盐水组(NS,n=12).VIP组大鼠在行CLP术后即刻给予6 nmol VIP,应用酶联免疫吸附试验(ELISA)检测各组大鼠血清谷丙转氨酶ALT和谷草转氨酶AST水平,同时检测血清炎症因子:促炎因子肿瘤坏死因子-α(TNF-α),抑炎因子白介素-10(IL-10)的变化;取大鼠肝脏组织行病理检查.在6 h以后的各时间点,与NS组比较,VIP组TNF-α水平明显降低,IL-10水平持续升高,VIP组AST和ALT水平自12 h始明显降低,肝脏病理损伤明显改善.实验表明,VIP通过抑制促炎因子的生成并促进抗炎因子的产生在大鼠脓毒性休克肝损伤中发挥保护作用.     

Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients

The effect of dietary amino acid taurine on the liver function of chronic hepatitis patients was investigated. The 24 chronic hepatitis patients with 2-5 times over normal activities of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were selected and equally divided into taurine treatment and control groups. In taurine treatment group, each patient took 2 g taurine 3 times a day for three months, and then stopped treatment for 1 month. Patients taking placebo without taurine for 4 months served as a control group. ALT and AST activities and levels of cholesterol, triglyceride and thiobarbituric acid relative substances of serum plasma in the taurine group were all decreased at the end of three month treatment. The study suggested that dietary amino acid taurine may ameliorate liver injury for chronic hepatitis patients.     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury

Introduction: Sepsis can result in acute lung injury. LL-37 is a small cationic host defense peptide involved in anti-inflammatory. In the current study, it was hypothesized that antimicrobial peptide LL-37 could play a protective role in attenuating the progression of sepsis-induced acute lung injury. Methods: Forty male C57BL/6 mice were induced into sepsis using cecal ligation and puncture, and subsequently administered with recombinant mouse osteopontin. Peptides LL-37, the LL-37 analog (FF/CAP18, called sLL-37), or normal saline was intravenously administered into septic mice for 20 hours. Then, proinflammatory cytokines (IL-6 and IL-1β), acute lung injury markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]), the neutrophil infiltration marker (myeloperoxidase [MPO]), and neutrophil infiltration were detected. Furthermore, the neutrophil migration and expression of migration-related factors (focal adhesion kinase [FAK], ERK, and P38) in differentiated HL-60 cells were detected. Results: Septic mice had upregulated IL-6, IL-1β, ALT, AST, LDH, MPO, p-FAK, p-ERK, and p-P38, infiltrated neutrophils, and migrated neutrophil-like HL-60 cells. In contrast, the administration of peptide LL-37 and sLL-37 inhibited all these changes. Compared with septic mice, it was found that proinflammatory cytokines, lung injury markers, MPO, and infiltrated neutrophils decreased in mice treated with LL-37 and sLL-37. In addition, the migrated neutrophil-like HL-60 cells and activated p-FAK, p-ERK, and p-P38 proteins were suppressed by LL-37 and sLL-37 treatments. Conclusions: Peptide LL-37 and its analog sLL-37 attenuated the progression of sepsis-induced acute lung injury by inhibiting neutrophil infiltration and migration through the FAK, ERK, and P38 pathways.     

Bee Venom Phospholipase A2 Protects against Acetaminophen-Induced Acute Liver Injury by Modulating Regulatory T Cells and IL-10 in Mice

The aim of this study was to investigate the protective effects of phospholipase A2 (PLA2) from bee venom against acetaminophen-induced hepatotoxicity through CD4⁺CD25⁺Foxp3⁺ T cells (Treg) in mice. Acetaminophen (APAP) is a widely used antipyretic and analgesic, but an acute or cumulative overdose of acetaminophen can cause severe hepatic failure. Tregs have been reported to possess protective effects in various liver diseases and kidney toxicity. We previously found that bee venom strongly increased the Treg population in splenocytes and subsequently suppressed immune disorders. More recently, we found that the effective component of bee venom is PLA2. Thus, we hypothesized that PLA2 could protect against liver injury induced by acetaminophen. To evaluate the hepatoprotective effects of PLA2, C57BL/6 mice or interleukin-10-deficient (IL-10^−/−) mice were injected with PLA2 once a day for five days and sacrificed 24 h (h) after acetaminophen injection. The blood sera were collected 0, 6, and 24 h after acetaminophen injection for the analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PLA2-injected mice showed reduced levels of serum AST, ALT, proinflammatory cytokines, and nitric oxide (NO) compared with the PBS-injected control mice. However, IL-10 was significantly increased in the PLA2-injected mice. These hepatic protective effects were abolished in Treg-depleted mice by antibody treatment and in IL-10^−/− mice. Based on these findings, it can be concluded that the protective effects of PLA2 against acetaminophen-induced hepatotoxicity can be mediated by modulating the Treg and IL-10 production.