Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

Biochanin A, an isoflavone existed in red clover and peanuts, has been reported to possess a wide spectrum of pharmacological activities, such as anti-inflammatory and antioxidant effects. However, the protective effects and mechanism of biochanin A on liver injury have not been reported. In this study, acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (D-GalN). Biochanin A was administrated 1 h prior to LPS/D-GalN challenge. Serum ALT, AST, IL-1β, and TNF-α levels, hepatic malondialdehyde (MDA), GPx, SOD, and Catalase contents, tissue histology, IL-1β, TNF-α, NLRP3, and Nrf2 expression were detected. The results showed that serum ALT, AST, IL-1β, and TNF-α levels and hepatic MDA content increased after LPS/GalN treatment. These changes were attenuated by biochanin A. Meanwhile, biochanin A dose-dependently up-regulated the expression of Nrf2 and HO-1. Biochanin A also inhibited hepatic IL-1β and TNF-α expression in a dose-dependent manner. Biochanin A did not inhibit LPS/D-GalN-induced hepatic NLRP3, ASC, and caspase-1 expression. However, the interaction of NLRP3 with ASC and caspase-1 were inhibited by biochanin A. In addition, LPS/D-GalN-induced up-regulation of thioredoxin-interacting protein (TXNIP) and interaction between TXNIP and NLRP3 were also inhibited by biochanin A. In conclusion, biochanin A protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.     

Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation,and attenuates experimental colitis in an IL-10 independent manner

Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis. In an in vitro study, we found that LPS induced the secretion of cytokines (i.e., IL-8 in COLO 205; TNF-α, IL-6, IL-12, and IL-10 in RAW 264.7; and TNF-α, IL-6 and IL-12 in peritoneal macrophages obtained from IL-10-deficient [IL-10^−/−] mice). Butyrate (100 μM and 500 μM) inhibited pro-inflammatory cytokine production (i.e., IL-8 in COLO205 and TNF-α, IL-6 and IL-12 in macrophages) but promoted anti-inflammatory cytokine (i.e., IL-10) production in RAW264.7 cells. Butyrate attenuated both the LPS-induced degradation/phosphorylation of IκBα and DNA binding of NF-κB and enhanced histone H3 acetylation. To confirm that butyrate played a protective role in colitis, an acute colitis model was induced using dextran sulfate sodium (DSS) and a chronic colitis model was induced in IL-10^−/− mice. The administration of oral butyrate (100 mg/kg) significantly improved histological scores in both colitis models, including the IL-10^−/− mice. In immunohistochemical staining, IκBα phosphorylation was attenuated, and histone H3 acetylation was reversed in the treated colons of both colitis models. Our results indicate that oral supplementation with butyrate attenuates experimental murine colitis by blocking NF-κB signaling and reverses histone acetylation. These anti-colitic effects of butyrate were IL-10-independent. Butyrate may therefore be a therapeutic agent for colitis.     

Chronic dexamethasone treatment results in hippocampal neurons injury due to activate NLRP1 inflammasome in vitro

Neuroinflammation mediated by NLRP-1 inflammasome plays an important role in the pathogenesis of neurodegeneration diseases such as Alzheimer's disease (AD). Chronic glucocorticoids (GCs) exposure has deleterious effect on the structure and function of neurons and was found to be correlated with development and progression of AD. We hypothesize that chronic glucocorticoids may down-regulate the expression of glucocorticoids receptor (GR) and activate NLRP-1 inflammasome in hippocampal neurons, which may promote neuroinflammation and induce neuronal injury. The present results showed that chronic DEX exposure significantly increased LDH release and apoptosis, decreased MAP2 and GR expression in hippocampal neurons. DEX (5 μΜ) exposure for 3 d significantly increased the expression of NLRP-1, ASC, caspase-1 and IL-1β in the hippocampal neurons and the release of IL-1β and IL-18 in the supernatants. Moreover, DEX (1, 5 μΜ) treatment for 3 d significantly increased the expression of NF-κB in hippocampal neurons. The GR antagonist, mifepristone (RU486), had protective effects on chronic DEX induced hippocampal neurons injury and NLRP1 inflammasome activation. The results suggest that chronic GCs exposure can decrease GR expression and increase neuroinflammation via NLRP1 inflammasome and promote hippocampal neurons degeneration, which may play an important role in the progression and development of AD.     

Le Carbone,a charcoal supplement,modulates DSS-induced acute colitis in mice through activation of AMPKα and downregulation of STAT3 and caspase 3 dependent apoptotic pathways

Le Carbone (LC) is a charcoal supplement, which contains a large amount of dietary fibers. Several studies suggested that charcoal supplement may be beneficial for stomach disorders, diarrhea, gas and indigestion. But no studies address whether LC intake would suppress inflammation, cell proliferation or disease progression in colitis. In the present study, the effect of LC on experimental colitis induced by dextran sulfate sodium (DSS) in mice and its possible mechanism of action were examined. A study was designed for 8 days, using C57BL/6 female mice that were administered with 3% DSS in drinking water for 7 days followed by another 1 day consumption of normal water with or without treatment. LC suspension was administered daily for 7 days via oral gavage using 5 mg/mouse in treatment group and normal group was supplied with drinking water. LC suspension significantly attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic changes were significantly reduced by LC treatment. The inflammatory mediators TNFα, IL-1β, p-STAT3 and p-NF-κB induced in the colon by DSS were markedly suppressed by LC. The increased activation of AMPKα in the colon was also detected in LC group. Furthermore, the apoptotic marker protein cleaved caspase 3 was down-regulated and anti-apoptotic proteins Bcl2 and Bcl-xL were significantly up-regulated by LC treatment. Taken together, our results demonstrate the ability of LC to inhibit inflammation, apoptosis and give some evidence for its potential use as adjuvant treatment of inflammatory bowel disease.     

NecroX-5 alleviate lipopolysaccharide-induced acute respiratory distress syndrome by inhibiting TXNIP/NLRP3 and NF-κB

The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidative stress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit the effects of anti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1β, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signal pathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB.     

Protective effect of linalool against lipopolysaccharide/d-galactosamine-induced liver injury in mice

Linalool, a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. The aim of this study was to investigate the effects of linalool against lipopolysaccharide (LPS)/d-galactosamine (GalN)-induced liver injury in mice. Mice were administered with linalool 1 h before receiving LPS (50 μg/kg) and GalN (800 mg/kg). The results demonstrated that linalool had a protective effect on LPS/GalN-induced acute liver injury, as evidenced by the attenuation of hepatic pathological damage, malondialdehyde (MDA) content, MPO activity and serum ALT and AST levels. Linalool alleviated serum and hepatic TNF-α and IL-6 production, as well as hepatic iNOS and COX-2 expression by inhibiting NF-κB activation. Treatment of linalool increased bcl-2 expression and inhibited caspase-3 and caspase-8 expression. In addition, linalool increased Nrf2 and heme oxygenase-1 expression up-regulation by LPS/GalN. In conclusion, our results suggested that linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition.     

NLRP3基因敲除增强芹菜素对triton-WR 1339所致高脂血症的降血脂及抗炎作用研究

目的探讨NLRP3对芹菜素降血脂和抗炎作用的干预及调控机制。方法采用Triton-WR1339对野生型(widetype,WT)C57BL/6小鼠和NLRP3-/-小鼠致高脂血症,给药组连续5 d灌胃给予芹菜素6.25 mg·kg^-1,收集血样及肝脏,测定血清中TC、TG、HDL、LDL;肝脏进行HE染色分析;ELISA测定血清中IL^-1β、IL-6、MCP-1含量。RT-qPCR测定肝脏中NLRP3、IL-4、ASC、CD36、CYP7A1、FGF21的mRNA表达水平。结果与NLRP3-/-模型组相比较,芹菜素降低NLRP3-/-模型小鼠血清TC、TG、LDL-C、IL^-1B、IL-6、MCP-1含量,提高HDL-C含量(P<0.05),减少肝脏脂肪病变比例;芹菜素对WT模型小鼠未见此作用。芹菜素均能上调WT和NLRP3-/-模型小鼠CD36、vLDLR的表达,抑制ASC、IL-4表达(P<0.05)。芹菜素仅调控NLRP3-/-模型小鼠的FGF21、CYP7A1的表达(P<0.05),对WT模型小鼠无作用。结论NLRP3基因敲除增强低剂量芹菜素改善Triton-WR 1339所致的高脂血症及炎症等症状。NLRP3基因敲除增强芹菜素调控血脂作用的机制可能为:NLRP3炎症小体缺失,从而增强芹菜素对FGF21/CYP7A1信号通路的调控相关。     

Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice

This study was designed to investigate the anti-inflammatory activity of the pure compound gentiopicroside (Gent) on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms. Experimental colitis was induced in ICR mice by dissolving 5% DSS in their drinking water for 7 days. Gent (200, 100, and 50 mg/kg) and 5-aminosalicylic acid (5-ASA, 100 mg/kg) were oral administrated once a day for 7 days. Anti-inflammatory effects were evaluated by comparing extend of colonic mucosal injury assessed by disease activity index (DAI), colon length, histopathological examination, and biochemical test. The possible mechanisms of Gent activities were explored by evaluating expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 using real-time fluorogenic PCR and expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) using Western blotting. The results showed that oral administration of Gent significantly attenuated DSS-induced loss of body weight, diarrhea, shortening of colon length and histological changes, associated with the decrease in the activity of myeloperoxidase (MPO) in the colon. In addition, the mRNA expression of TNF-α, IL-1β, IL-6 and the overexpression of COX-2 and iNOS proteins in the colon were down-regulated by Gent treatment. To our knowledge, this is the first study to demonstrate that Gent treatment can exert anti-inflammatory effects on experimental acute colitis through attenuating the expression levels of TNF-α, IL-1β, IL-6, iNOS and COX-2, and it may present the therapeutic potential in the treatment of colitis.     

BPA-induced apoptosis of rat Sertoli cells through Fas/FasL and JNKs/p38 MAPK pathways

Bisphenol-A was examined for its effects on cultured Sertoli cells established from 18 to 22-day-old rat testes. Results indicated that exposure to BPA (0, 30, 50 and 70 μM) decreased the cell viability in a concentration-dependent manner and induced cell apoptosis. Apoptosis-caused cell death was observed in cells exposed to 50 and 70 μM BPA. The mRNA expressions of Fas, FasL and caspase-3 were all elevated, and the protein expressions of FasL and cleaved caspase-3 were also increased. In addition, levels of phosphorylation of JNKs/p38 MAPK were also increased and then activated JNKs/p38 MAPK up regulated target gene expressions, such as c-jun and CHOP. Translocation of NF-κB into nuclei indicated the activation of NF-κB after treatment with BPA. Taken together, observed results suggest that BPA induces apoptosis of Sertoli cells by the activation of JNKs/p38 MPAK and translocation of NF-κB, and Fas/FasL system plays a critical role in the initiation of apoptosis.     

Protective role of liriodendrin in mice with dextran sulphate sodium-induced ulcerative colitis

Sargentodoxa cuneata, containing syringaresinol and its glycoside liriodendrin as the main bioactive compounds, is a well-known traditional Chinese medicine for treating intestinal inflammation. In our preliminary study, liriodendrin inhibited NF-kB activation in sepsis-induced acute lung injury. The present study was designed to investigate its effect on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms. Experimental colitis was established by giving mice drinking water containing 3% (w/v) DSS for 7 days. The mice were pretreated with liriodendrin (100 mg/kg/day, intragastrically) 3 days before DSS treatment. We determined the effects of liriodendrin on disease activity index (DAI), colon length, histopathological examination, antioxidants, and anti-inflammatory activities. Our results showed that liriodendrin greatly decreased MPO and MDA activities and significantly increased SOD and GPx activities in the colon. Moreover, liriodendrin improved DAI, colon length and histological damage in colon and reduced the levels of pro-inflammatory cytokines, such as TNF-a, IL-1β and IL-6. Meanwhile, assessments by western blot revealed that liriodendrin significantly suppressed the activation of Akt and NF-κB pathways and up-regulated the expression of ERβ in the colon. In vitro, liriodendrin down-regulated production of pro-inflammatory cytokines and suppressed NF-κB signalling pathways in LPS-induced RAW 264.7 macrophages in a concentration-dependent manner. In addition, syringaresinol, the hydrolysate of liriodendrin, more potently down-regulated production of pro-inflammatory cytokines and suppressed NF-κB and Akt signalling pathways in LPS-induced RAW 264.7 macrophages,which were abolished by using a pure ER antagonist, ICI182, 780. Taken together, liriodendrin-mediated suppression of inflammatory damage in the colon may be attributable to the in vivo transformation to syringaresinol and liriodendrin may be a promising therapeutic approach preventive agent for colitis treatment.     

Dextran sulfate sodium-induced acute experimental colitis in C57BL/6 mice is mitigated by selenium

BackgroundSodium selenite has been shown to have a protective role in experimental colitis. Th1 and Th17 responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis and inflammatory bowel disease. This study investigated whether sodium selenite can suppress Th1/Th17-mediated experimental colitis.MethodsMice were administered sodium selenite (2 μg/g body weight) by gavage daily for 30 days. Beginning on day 21, mice were administered 2.5% oral DSS for 9 days. The mice were sacrificed on day 31. Survival rates, clinical symptoms, colon lengths, and histological changes were determined.ResultsPretreatment with sodium selenite (2 μg/g body weight) improved survival rates, colon shortening, body weight loss, disease activity index, and histopathological score in mice with DSS-induced colitis. Pretreatment with sodium selenite restored interleukin-10 and Foxp3 excretion, as well as reducing the levels of interferon-γ and interleukin-17A.ConclusionsPretreatment with sodium selenite showed therapeutic potential for preventing colitis in mice. This effect may be mediated by the immunomodulation of regulatory T cells, expressing anti-inflammatory genes that suppress Th1 and Th17 responses.     

Establishment and validation of a new semi-chronic dextran sulfate sodium-induced model of colitis in mice

BackgroundThe dextran sulfate sodium (DSS)-induced model of colitis is a commonly used model of inflammatory bowel disease (IBD) in animals. However, there were few studies on the therapeutic efficacy of drugs for IBD after the onset of colitis in this model. We established a semi-chronic model of DSS-induced colitis in mice and used it to assess the therapeutic efficacy of agents for IBD.Materials and methodsColitis was induced by administration of 3% DSS in drinking water to mice for 7 days followed by 5 days of normal drinking water.ResultsUlcerative colitis (UC)-like symptoms including diarrhea, bloody stools and body-weight loss were observed from days 3 to 5, and continued until day 12 after DSS administration. Persistent colitis was associated with sustained local production of cytokines and was characterized by infiltration of inflammatory cells, crypt loss and erosion in the distal colon. These features are similar to those found in patients with UC. In this model, anti-tumor necrosis factor (TNF)-α antibody or anti-interleukin (IL)-12/23p40 antibody significantly ameliorated colitis when administered after the onset of colitis. However, treatment with FK506, prednisolone or sulfasalazine provided limited therapeutic benefit.ConclusionThe DSS-induced colitis established here showed similar symptomatic and histopathological features to those seen in human UC. This model may be available for predicting the clinical efficacy of candidate compounds for UC.     

Neurogenic contraction of mouse rectum via the cyclooxygenase pathway: Changes of PGE2-induced contraction with dextran sulfate sodium-induced colitis

Recent reports suggest that cyclooxygenases (COXs) including COX-2 are constitutively expressed, and prostaglandins (PGs) regulate motility and/or contraction in the colon and rectum. This study examines the role of COXs in the regulation of neuromuscular function in longitudinal preparations of isolated rectum and distal colon (Side A, close to the transverse colon; and Side B, close to the rectum) in normal mice and after the induction of colitis by dextran sulfate sodium (DSS). In control rectum, electrical stimulation (ES)-induced contractions were inhibited by atropine and by COX inhibitors, in an independent manner. PGE₂ at 3 μM caused a marked contraction, but the secondary response at 20 min after the first application was 60% desensitized. In rectum from DSS-treated mice, spontaneous and ES-induced contractions were significantly less intense than in the control preparations, and the response to PGE₂ was abolished but that to 3 μM acetylcholine was not. In control distal colon, the responses to PGE₂ in neither side were desensitized by the repeated application. In DSS-treated distal colon, PGE₂ response was impaired in the two regions, and was desensitized on Side B more than Side A. DSS treatment impaired contractions by 40 mM KCl in rectum and on Side B but not Side A. DSS treatment increased COX-2 expression in rectum, but not in distal colon. These findings suggest that the induction of colitis by DSS affects ES- and PGE₂-regulated motility in the order rectum > distal colon close to the rectum > distal colon in mice.     

Ameliorative effects of 3,4-oxo-isopropylidene-shikimic acid on experimental colitis and their mechanisms in rats

The aim of the present study was to investigate the therapeutic effect and mechanism of 3,4-oxo-isopropylidene-shikimic acid (ISA) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. (50, 100, 200 mg/kg) was administered for 14 days, 1 day after the induction of colitis by TNBS. The colonic injury and inflammation were assessed by macroscopic damage scores and myeloperoxidase (MPO) activity. Malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in plasma were measured with biochemical methods. Prostaglandin E₂ (PGE₂) level in colon was determined by radioimmunoassay. Expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), inhibitor kappa B-alpha (IκBα) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry. Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with TNBS, which was manifested as the significant increase in colon mucosal damage index, MPO activity, levels of MDA, NO and PGE₂, as well as the expressions of iNOS, COX-2 and NF-κB p65 proteins in the colonic mucosa, and the significant decrease in expressions of IκBα proteins in the colonic mucosa. However, these parameters were found to be significantly ameliorated in rats treated with ISA at given doses, especially at 100 mg/kg and 200 mg/kg. Administration of ISA may have significant therapeutic effects on experimental colitis in rats, probably due to its mechanism of antioxidation, its inhibition of arachidonic acid metabolism and its modulation of the IκBα/NF-κB p65 expression.     

益母草碱抑制NLRP3炎症小体过度激活调控巨噬细胞M1/M2表型分化

目的研究益母草碱对脂多糖(LPS)诱导小鼠腹腔巨噬细胞免疫应答影响及相关机制。方法分离小鼠腹腔巨噬细胞,用脂多糖和益母草碱预处理24 h,MMT法检测巨噬细胞活性;Griess法检测NO释放量;ELISA法检测IL-1β、IL-18、IL-6、TNF-α的释放量;RT-PCR法检测NLRP3、ASC、caspase-1、TNF-α、iNOS、Arg-1和CD206的mRNA表达量;Western blot检测NLRP3、ASC、caspase-1蛋白表达量。结果益母草碱能显著抑制脂多糖引起的巨噬细胞上清液中NO、IL-1β、IL-18、IL-6、TNF-α的释放。RT-PCR及Western blot实验结果显示,益母草碱可以抑制脂多糖引起的巨噬细胞中NLRP3、ASC、caspase-1的mRNA及蛋白表达;益母草碱还能明显抑制脂多糖所诱导的巨噬细胞向M1型分化,并促进巨噬细胞向M2型分化。结论益母草碱能通过抑制NLRP3炎症小体,促进脂多糖诱导的巨噬细胞由M1表型向M2表型分化。     

Effects of quercetin on mRNA expression of steroidogenesis genes in primary cultures of Leydig cells treated with atrazine

The effect of the phytoestrogen, quercetin (QT) on the reproductive toxicity of atrazine (ATZ) was explored in interstitial Leydig cells (ILCs). We measured the mRNA expressions of steroidogenesis genes: steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome-P450 (CYP) 11A1, insulin-like factor 3 (INSL-3), CYP17A1, inhibin-α (INH-α), androgen receptor (AR), estrogen receptor-α (ER-α), and luteinising hormone receptor (LHR) in isolated ILCs by real-time-PCR after cultured cells were treated in vitro with ATZ (232 μM) and QT (50 μM). The mRNA expression of tested genes increased with ATZ treatment and was normalized by quercetin except AR and ER-α expression. Treatment of cells with QT alone (15–50 μM) caused a dose-dependent increase in AR and ER-α mRNA expression. We also found that QT (50 μM) increased the expressions of AR and ER-α in the presence of a sub-threshold level of cyclic-AMP at 1 h culture period to the levels seen with maximal stimulation of cyclic-AMP. Furthermore, the expressions of tested genes were unaffected by cyclic-AMP at 6 h when the stimulatory effects of ATZ on tested genes were sustained. These findings suggest that ATZ may stimulate the expression of tested steroidogenesis genes in ILCs via a mechanism independent of cyclic-AMP which was partially antagonize by QT.     

Involvement of hypoxia-inducible factor-1α in the oxidative stress induced by advanced glycation end products in murine Leydig cells

Hyperglycemia increases the formation of advanced glycation end products (AGEs), triggers oxidative impairments and influences inducible factor (HIF)-1α protein levels and transactivation function. Compromised HIF-1α in testis leads to male infertility. The aim of the study was to investigate the role of HIF-1α in oxidative stress induced by AGEs in murine Leydig TM3 cells. TM3 cells were treated with 50 μg/ml of AGEs, or HIF-1α siRNA or 500 μM of DMOG (dimethyloxalylglycine) respectively. The cells were also pretreated with HIF-1α siRNA or 500 μM of DMOG and then were treated with 50 μg/ml of AGEs. The formation of reactive oxygen species (ROS) and cell apoptosis was evaluated. The expression of caspase-3, Heme oxygenase (HO)-1, steroidogenic acute regulatory protein (StAR) and cytochrome P450 17α polypeptide 1 (CYP17A1) was examined by Western blotting. AGEs increased ROS production, induced apoptosis and activated HIF-1α and HO-1 in TM3 cells. HIF-1α attenuated the AGE-induced ROS formation and promoted apoptosis via the upregulation of caspase-3. Knockdown of HIF-1α inhibited the expression of CYP17A1 and StAR, and enhanced the inhibition of StAR and CYP17A1 by AGEs. These findings indicate that attenuated HIF-1α exacerbates the oxidative stress injury by AGEs in murine Leydig cells, and contributes to diabetic male infertility.     

Protective effect of Lactobacillus plantarum 21, a probiotic on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats

Inflammatory mediators play a crucial role in ulcerative colitis (UC). The present study was aimed to evaluate the effects of Lactobacillus plantarum 21 (LAB 21) on inflammatory mediators in trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The inflammatory response was assessed by changes in colon morphology, histopathology, and measurement of reduced glutathione (GSH), lipid peroxidation (TBARS), nitric oxide (NO), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and interleukin 10 (IL-10) mRNA and protein levels by ELISA. Besides, protein expressions of IL-1β and IL-10 were also evaluated by western blot. Treatment with LAB 21 (1 × 10¹⁰ CFU/rat/day) and sulfasalazine (500 mg kg^− 1 body weight) for 14 days after induction of colitis, significantly decreased TBARS, NO and increased GSH concentration. The protein and mRNA expressions of IL-1β and TNFα were down-regulated, whereas, protein and mRNA expression of IL-10 was up-regulated in LAB 21-treated rats. Moreover, LAB 21 attenuated the macroscopic colonic damage, histopathological changes induced by TNBS. These results suggest that LAB 21 may be effective in the treatment of UC by immunomodulatory and antioxidant properties.