Protective mechanisms of anthocyanins from purple sweet potato against tert-butyl hydroperoxide-induced hepatotoxicity

Anthocyanins have been shown to exert anti-proliferative, anti-inflammatory effects and anti-carcinogenic activity. In the present work, we investigated the protective effects of anthocyanin fraction (AF) from purple sweet potato on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in HepG2 cell line and in rat liver. The result showed that the oral pretreatment of AF before t-BHP treatment significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress of the liver by evaluation of malondialdehyde and glutathione. Histopathological evaluation of the livers also revealed that AF reduced the incidence of liver lesions. The in vitro result showed that AF significantly reduced t-BHP-induced oxidative injury, as determined by cell cytotoxicity, intracellular glutathione content, lipid peroxidation, reactive oxygen species (ROS) levels, and caspases activation. Also, AF up-regulated antioxidant enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone reductase, and glutathione S-transferase. Moreover, AF induced Nrf2 nuclear translocation and Akt and ERK1/2 activation, pathways that are involved in inducing Nrf2 nuclear translocation. Taken together, these results suggest that the protective effects of AF against t-BHP-induced hepatotoxicity may, at least in part, be due to its ability to scavenge ROS and to regulate the antioxidant enzyme HO-1 via the Akt and ERK1/2/Nrf2 signaling pathways.     

Protective effect of linalool,myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells

We studied the protective effect of monoterpenes myrcene, eucalyptol and linalool against t-butyl hydroperoxide (t-BOOH) induced genotoxicity in reverse mutation assay with Escherichia coli WP2 IC185 strain and its oxyR mutant IC202, and with the comet assay in human hepatoma HepG2 and human B lymphoid NC–NC cells. The monoterpenes were tested in concentration ranges 0.05–1.5 mg/plate and 0.01–1.0 μg/ml in bacteria and mammalian cells, respectively. Suppression of t-BOOH induced mutagenesis was detected only in IC202 strain, and correlated with the observed inhibition of lipid peroxidation by the three monoterpenes. Linalool and myrcene strongly suppressed t-BOOH induced mutagenesis. Eucalyptol, in addition to moderate suppression of t-BOOH induced mutagenesis, suppressed also spontaneous mutagenesis. In NC–NC cells linalool and myrcene reduced t-BOOH induced DNA damage by about 50% at 0.01 μg/ml, while eucalyptol was less efficient (about 50% reduction at 1.0 μg/ml). In HepG2 cells linalool and eucalyptol reduced DNA damage by 30% and 40%, respectively, while myrcene was ineffective. The repair of t-BOOH induced DNA damage, studied in HepG2 cells, was not affected by monoterpenes. The results indicate that linalool, eucalyptol and myrcene have substantial protective effect against oxidant induced genotoxicity, which is predominately mediated by their radical scavenging activity.     

Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide

Although tert-butyl hydroperoxide (t-BHP) is commonly used to induce oxidative stress, little is known about the time- or dose-dependence of its oxidative effects. In this study, we examined hepatotoxicity and oxidative stress in male rats at various times (0–24 h) after t-BHP (0, 0.2, 0.5, 1 or 3 mmol/kg, ip) treatment. Serum hepatotoxicity parameters were increased from 2 h following 1 mmol/kg t-BHP and reached their maximum values at 8 h. Plasma malondialdehyde levels were maximally elevated by 62% at 0.5 h and returned to control levels by 4 h. Hepatic glutathione levels were decreased between 0.5 and 2 h, and hepatic glutathione disulfide levels were increased at 2 h. Interestingly, hepatic glutathione levels were increased at 24 h, which may be attributed to up-regulation of glutathione synthesis through induction of gamma-glutamylcysteine ligase expression. The elevation of hepatotoxic parameters and plasma MDA was observed from 0.5 to 1 mmol/kg t-BHP, respectively, in a dose-dependent manner. Considering that the maximal dose resulted in 20% lethality, 1 mmol/kg of t-BHP may be suitable for evaluating antioxidant activity of tested compounds. Our results provide essential information to characterize the t-BHP-induced oxidative stress and hepatotoxicity.     

Protective effects of dried flower extracts of Hibiscus sabdariffa L. against oxidative stress in rat primary hepatocytes

Dried flower extracts of Hibiscus sabdarrifa L., a local soft drink material and medical herb, was found to possess antioxidant activity in the present study. In the preliminary studies, antioxidant potential of three fractions of the ethanol crude extract (HS-C: chloroform-soluble fraction; HS-E: ethyl acetate soluble fraction; HS-R: residual fraction) obtained from the dried flowers of Hibiscus sabdarrifa L. were evaluated by their capacity of quenching 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and inhibiting xanthine oxidase (XO) activity. HS-E showed the greatest capacity of scavenging free radical (EC₅₀ = 0.017 mg/ml), and HS-C showed the strongest inhibitory effect on XO activity (EC₅₀ = 0.742 mg/ml). Furthermore, antioxidant bioactivities of these crude extracts were investigated using a model of tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in rat primary hepatocytes. All fractions were found to inhibit significantly the unscheduled DNA synthesis (UDS) induced by t-BHP at a concentration of 0.20 mg/ml. HS-C and HS-E also decreased the leakage of lactate dehydrogenase (LDH) and the formation of malondialdehyde (MDA) induced by t-BHP (1.5 m ) considerably at a concentration of 0.10 and 0.20 mg/ml in the rat primary hepatocyte cultures. These results indicated that the dried flower extracts (HS-C and HS-E) of H. sabdarrifa L. protect rat hepatocytes from t-BHP-induced cytotoxicity and genotoxicity by different mechanisms.     

Protective role of sitagliptin against oxidative stress in a kainic acid-induced status epilepticus in rats models via Nrf2/HO-1 pathway

Aim: Sitagliptin (Sita) is a dipeptidyl peptidase-4 inhibitor which has been approved as a curing medicine for Type 2 diabetes (T2D) and has also reported its neuroprotective and antioxidant activity. This article describes the therapeutic effects of Sita on induced rat model of SE by kainic acid (KA) and investigated the antioxidative pathway of sita. Methods: Sprague–Dawley male rats were used randomly divided in four groups: vehicle control, KA and Sita + KA in a 5 and 10 mg/kg doses respectively in further groups. SE in rats was induced by the administration of KA in Phosphate buffered saline (PBS) intraperitoneally (IP) in a dose of 15 mg/kg. Seizure intensity, oxidative stress parameters, TUNEL assay, histopathology, and Nrf2/HO-1 expressions were evaluated. Results: Increment in the latency in SE results in delaying the initiation of disease in the pretreated rats by Sita compared to induce group (KA) as well the percentage of occurrence of SE was decreased. The content of MDA elevates whereas the SOD production decreases on administering the KA at various time intervals. Sita shows protective action against the KA-induced SE by reducing the oxidative stress thus inhibiting the change in SOD and MDA was observed after KA administration prior SE onset. Based on the above results, the study explains possible molecular mechanism of Sita. Sita Pretreatment showed significant elevation in expression of Nrf2 and HO-1 proteins in hippocampus region of the brain. Conclusion: Above parameters defines the potential effect of Sita on brain injury occurred due to SE by anti-oxidative pathway.     

Protective effects of Forsythia suspensa extract against oxidative stress induced by diquat in rats

Forsythia suspensa extract has been proved as a potential antioxidant in the recent years. The present study was undertaken to obtain the optimal antioxidant fraction in vitro and examine its antioxidative potential against diquat-induced oxidative stress in male Sprague Dawley rats in vivo. In vitro, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging experiment indicated that the CH₂Cl₂ fraction of F. suspensa (FSC) exerted the strongest scavenging activities; forsythoside A, forythialan A and phillygenin from it might be the major antioxidant constituents. In vivo, pretreatment of rats with different doses of FSC (25, 50 and 100 mg/kg bw) and vitamin C (100 mg/kg bw, positive control) for 15 days significantly lowered the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in plasma compared to the negative control group. Also, FSC significantly increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of glutathione (GSH) in plasma, liver and kidney whereas it decreased the levels of malondialdehyde (MDA) in plasma and kidney. Moreover, the protective effect of FSC (100 mg/kg bw) was better than vitamin C. These results revealed that FSC exerted a protective effect against diquat-induced oxidative stress and is worthy of becoming a potential dietary antioxidant.     

Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes

Isorhamentin is a 3′-O-methylated metabolite of quercetin, and has been reported to have anti-inflammatory and anti-proliferative effects. However, the effects of isorhamnetin on Nrf2 activation and on the expressions of its downstream genes in hepatocytes have not been elucidated. Here, we investigated whether isorhamnetin has the ability to activate Nrf2 and induce phase II antioxidant enzyme expression, and to determine the protective role of isorhamnetin on oxidative injury in hepatocytes. In HepG2 cells, isorhamnetin increased the nuclear translocation of Nrf2 in a dose- and time-dependent manner, and consistently, increased antioxidant response element (ARE) reporter gene activity and the protein levels of hemeoxygenase (HO-1) and of glutamate cysteine ligase (GCL), which resulted in intracellular GSH level increases. The specific role of Nrf2 in isorhamnetin-induced Nrf2 target gene expression was verified using an ARE-deletion mutant plasmid and Nrf2-knockout MEF cells. Deletion of the ARE in the promoter region of the sestrin2 gene, which is recently identified as the Nrf2 target gene by us, abolished the ability of isorhamnetin to increase luciferase activity. In addition, Nrf2 deficiency completely blocked the ability of isorhamnetin to induce HO-1 and GCL. Furthermore, isorhamnetin pretreatment blocked t-BHP-induced ROS production and reversed GSH depletion by t-BHP and consequently, due to reduced ROS levels, decreased t-BHP-induced cell death. In addition isorhamnetin increased ERK1/2, PKCδ and AMPK phosphorylation. Finally, we showed that Nrf2 deficiency blocked the ability of isorhamnetin to protect cells from injury induced by t-BHP. Taken together, our results demonstrate that isorhamnetin is efficacious in protecting hepatocytes against oxidative stress by Nrf2 activation and in inducing the expressions of its downstream genes.     

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats

Aim and Objectives:

In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.

Materials and Methods:

PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.

Results:

The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).

Conclusion:

Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.     

葡萄籽原花青素联合亚低温通过ERK/Nrf2/HO-1通路对脑缺血再灌注损伤大鼠的保护作用

目的基于ERK/Nrf2/HO-1通路探讨葡萄籽原花青素(GSP)联合亚低温(MHT)对脑缺血再灌注损伤大鼠的脑保护作用。方法大鼠随机分为假手术组、模型组、MHT组、GSP组、MHT+GSP组。采用线栓法建立脑缺血再灌注损伤大鼠模型。评估各组大鼠神经功能缺损评分(NDS),TTC法观察并计算脑梗死面积,尼氏染色观察脑组织病理学变化,TUNEL法计算细胞凋亡指数,酶联免疫吸附法检测脑组织丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,Westernblotting检测Bax、Bcl-2、p-ERK1/2、Nrf2和HO-1蛋白表达。结果与假手术组比较,模型组大鼠NDS、脑梗死面积、AI、脑组织MDA水平、Bax、p-ERK1/2、胞质和胞核Nrf2、HO-1蛋白表达均显著升高(P<0.05),SOD、GSH-Px活力和Bcl-2蛋白表达显著降低(P<0.05)。与模型组比较,MHT组、GSP组和MHT+GSP组大鼠NDS、脑梗死面积、AI、脑组织MDA水平、Bax和胞质Nrf2蛋白显著降低(P<0.05),SOD、GSH-Px活力、Bcl-2、p-ERK1/2、胞核Nrf2、HO-1蛋白表达显著升高(P<0.05)。且MHT+GSP组的治疗疗效高于MHT组和GSP组。结论 MHT和GSP联合作用可能通过激活ERK/Nrf2/HO-1通路,上调p-ERK1/2、胞核Nrf2和HO-1蛋白表达,抑制氧化应激,发挥脑保护作用。     

Eriodictyol-7-O-glucoside,a novel Nrf2 activator,confers protection against cisplatin-induced toxicity

Eriodictyol-7-O-glucoside, a flavonoid isolated from Dracocephalum rupestre, is among the most potent free radical scavenger. In the present study, we identified eriodictyol-7-O-glucoside as a novel nuclear factor E2-related factor 2 (Nrf2) activator using a high-throughput cellular screening method. This compound activated Nrf2 signaling pathway and was able to stabilize Nrf2 by delaying Nrf2 degradation, resulting in accumulation of Nrf2 protein and activation of the Nrf2-dependent protective response. Recent studies have suggested that activation of Nrf2 pathway would confer protection against cisplatin-induced toxicity. The protective role of eriodictyol-7-O-glucoside in cisplatin-induced toxicity was investigated in a human renal mesangial cell line, HRMC. Cotreatment of HRMC cells with eriodictyol-7-O-glucoside significantly improved cell survival under cisplatin exposure. These findings demonstrated the feasibility of using natural compounds targeting Nrf2 as a therapeutic approach to subvert the side effects of cisplatin in normal cells.     

Hepatoprotective and antioxidative effects of total phenolics from Laggera pterodonta on chemical-induced injury in primary cultured neonatal rat hepatocytes

Although Laggera pterodonta as a folk medicine has been widely used for several centuries to ameliorate some inflammatory ailments as hepatitis in China, there have been no studies of the hepatoprotective and antioxidative effects of this plant. In this paper, the hepatoprotective effect of total phenolics from L. pterodonta (TPLP) against CCI₄-, d-GalN-, TAA-, and t-BHP-induced injury was examined in primary cultured neonatal rat hepatocytes. TPLP inhibited the cellular leakage of two enzymes, hepatocyte ASAT and ALAT, caused by these chemicals and improved cell viability. Moreover, TPLP afforded much stronger protection than the reference drug silibinin. Meanwhile, DPPH and superoxide radicals scavenging activities of TPLP were also determined. The present investigation is the first to report chemical-induced injury model in primary cultured neonatal rat hepatocytes and provide evidence for the hepatoprotective and antioxidative effects of L. pterodonta. Neutralizing reactive oxygen species by nonenzymatic mechanisms may be one of main mechanisms of TPLP against chemical-induced hepatocyte injury. Furthermore, The total phenolic content of L. pterodonta and its main component type were quantified, and its principle components isochlorogenic acids were isolated and authenticated. These data support the folkloric uses of L. pterodonta in the treatment of hepatitis.     

Tadalafil alleviates cisplatin-induced reproductive toxicity through the activation of the Nrf2/HO-1 pathway and the inhibition of oxidative stress and apoptosis in male rats

Male reproductive toxicity is a well-known adverse effect of cisplatin (CIS), an important antineoplastic agent used to control several types of cancers. Tadalafil (TDF), is a long-acting phosphodiesterase-5 (PDE5) inhibitor commonly used as treatment for erectile dysfunction. The aim of this work was to study the possible protective effect of TDF against CIS-induced testicular toxicity in rats and the possible involvement of Nrf2/HO-1 pathway, which demonstrates antioxidant and inflammatory activities utilizing zinc protoporphyrin-IX (ZnPP) as HO-1 inhibitor. Results revealed that TDF attenuated the CIS-induced disturbances in sperm count and activities, normalized the serum testosterone level, improved the CIS-induced changes in epididymal and testicular weights and restored the normal structure of testicular tissues. In addition, TDF upregulated the gene expression levels of Nrf2 and HO-1 and the activity of HO-1 whereas, it reduced the CIS-induced changes in testicular oxidative stress markers and the levels of inflammatory mediators (TNF-α and iNOS). Furthermore, TDF antagonized the CIS-induced increase in testicular gene expression of apoptotic markers caspase-3 and Bax, and the decrease in Bcl-2. However, ZnPP co-administration significantly attenuated all TDF-mediated improvements in CIS-induced testicular toxicity, biochemical changes, and apoptosis. In conclusion, TDF exerts a protective effect against CIS-induced reproductive toxicity in males, through different mechanisms, besides its inhibitory action to PDE5, possibly mediated by the upregulation of Nrf2/HO-1, along with its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, the use of TDF represents a promising therapeutic approach to protect the male reproductive system from the harmful toxic effects of CIS.     

细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用

目的:研究细胞外信号调节激酶1/2(ERK1/2)抑制剂PD98059对大鼠内毒素弥散性血管内凝血(DIC)多器官损伤的保护作用。方法:Sprague-Dawley(SD)大鼠随机分为对照组、DIC组及抑制剂组。DIC组通过腹腔注射6mg/kg脂多糖(LPS)建立内毒素DIC模型,抑制剂组腹腔注射6mg/kg LPS和10mg/kg PD98059。5h后取血,利用全自动血凝仪及生化仪检测活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素(BUN)及肌酐(Cr)等指标;并留取心肝肾组织,光镜下观察其形态学变化。结果:与对照组相比:DIC组APTT、LDH、ALP、ALT、AST、BUN及Cr均延长或升高(P<0.01),FIB较对照组降低(P<0.01),心、肝、肾组织病理学检查均有明显的血管扩张充血;PD98059预防性用药后,除Cr外各指标均有明显改善(P<0.01),心、肝、肾组织血管充血减轻。结论:ERK1/2抑制剂PD98059能够减轻内毒素DIC时的多器官损伤,其机制与ERK1/2信号通路的抑制有关。     

Protective effects of quercetin against phenylhydrazine-induced vascular dysfunction and oxidative stress in rats.

Oxidative stress is a major contributor to the development of vascular dysfunction found in various pathological conditions. Quercetin, one of the potent antioxidant bioflavonoid compounds, has been shown to alleviate oxidative injury by modulation of gene expression leading to suppression of production of reactive oxygen and nitrogen species and conferring an antiapoptotic activity. The aim of the present study was to investigate the protective effects of quercetin in a model of phenylhydrazine (PHZ)-induced oxidant stress, vascular dysfunction and hemodynamic disturbance in rats. Male Sprague-Dawley rats were administered quercetin orally (25 or 50mg/kg/day) for 6 days. On day four, all animals except those in the normal control group, were administered PHZ intraperitoneally. The results showed that PHZ induced severe hemolysis. The mean arterial pressure and hindlimb vascular resistance of PHZ-control rats were markedly decreased compared to normal controls. Treatment with quercetin significantly improved arterial blood pressure and peripheral vascular resistance. Vascular responsiveness to bradykinin, acetylcholine, and phenylephrine in PHZ-control rats was dramatically suppressed and quercetin restored these responses in a dose-dependent manner. Quercetin partially protected blood glutathione, suppressed plasma malondialdehyde levels, and largely suppressed nitric oxide metabolites and superoxide anion production. These results provide the first evidence for the role of the flavonoid, quercetin, in the alleviation of vascular dysfunction in an animal model of PHZ-induced oxidant stress.     

Emodin protected against synaptic impairment and oxidative stress induced by fluoride in SH‐SY5Y cells by modulating ERK1/2/Nrf2/HO‐1 pathway

Excessive fluoride exposure contributes to neurotoxic effects. Emodin exhibits antioxidative functions in the central nervous system (CNS); however, its neuroprotective mechanism against fluoride remains to be elucidated. Our aim was to explore the neuroprotective efficacy and the possible mechanisms of emodin. In our study, synaptic proteins and oxidative stress damage were examined after human neuroblastoma SH‐SY5Y cells were treated with high doses of NaF for 24 hours. Moreover, pretreatment with emodin was used to shed light on the neuroprotective effects in NaF‐induced toxicity in SH‐SY5Y cells. We found that NaF significantly lowered the protein expressions of SNAP 25, synaptophysin and PSD 95 in SH‐SY5Y cells. In addition, NaF exposure increased the protein expression of p‐ERK1/2 and decreased the protein expressions of Nrf2 and HO‐1, as well as facilitated increasing ROS, 4‐hydroxynonenal (4‐HNE), and 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG). Pretreatment with emodin significantly recovered these alterations caused by NaF. These data implied that the neuroprotective effects of emodin and pointed to the promising utilization for protecting against neurotoxicity induced by fluoride.     

Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

Paraquat (1,1′-dimethyl-4,4′-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which was greater in differentiated cells. Paraquat treatment also resulted in increased expression of HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences in expression of these enzymes were evident between undifferentiated and differentiated cells. In contrast, expression of GSTA1-2 was significantly greater in differentiated relative to undifferentiated cells after paraquat treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat. These data demonstrate that paraquat induces oxidative stress in keratinocytes leading to increased expression of antioxidant genes. These intracellular proteins may be important in protecting the skin from paraquat-mediated cytotoxicity.     

Protective effects of fucoxanthin against ferric nitrilotriacetate-induced oxidative stress in murine hepatic BNL CL.2 cells

Fucoxanthin is a carotenoid that is rich in some seaweed. Although fucoxanthin has been reported to possess radical-scavenging activities in vitro, little is known whether it may protect against iron-induced oxidative stress in cultured cells. In this study, we examined the protection of fucoxanthin against oxidative damage in BNL CL.2 cells induced by ferric nitrilotriacetate (Fe-NTA). The data show that incubation of BNL CL.2 cells with Fe-NTA for 30 min significantly decreased cell proliferation, whereas pretreatment with fucoxanthin (1–20 μΜ) for 24 h significantly recovered cell proliferation in a dose-dependent manner. In addition, fucoxanthin pretreatment significantly decreased intracellular reactive oxygen species (ROS) and DNA damage in BNL CL.2 cells incubated with Fe-NTA for 30 min. Moreover, fucoxanthin markedly decreased the level of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl contents in BNL CL.2 cells induced by Fe-NTA. By contrast, fucoxanthin significantly increased the levels of GSH in a concentration-dependent manner. These results demonstrate that fucoxanthin at 1–20 μΜ effectively prevents cytotoxicity in BNL CL.2 cells treated with Fe-NTA, and that the protective effect is likely associated with decreased intracellular ROS, TBARS, protein carbonyl contents and increased GSH levels.