Epicatechin ameliorates ionising radiation-induced oxidative stress in mouse liver

Abstract

The current study was intended to evaluate the hepatoprotective effect of Epicatechin (EC) against radiation-induced oxidative stress, in terms of inflammation and lipid peroxidation. Swiss albino mice were administered with EC (15 mg/kg body weight) for three consecutive days before exposing them to a single dose of 5-Gy ⁶⁰Co gamma (γ) irradiation. Mice were necropsied and livers were taken for immunohistochemistry, western blot analysis and biochemical tests for the detection of markers of hepatic oxidative stress. Nuclear translocation of nuclear factor kappa B (NF-κB) and lipid peroxidation were increased whereas the activities of superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH) content and ferric reducing antioxidant power (FRAP) were diminished upon radiation exposure compared to control. Translocation of NF-κB from cytoplasm to nucleus and lipid peroxidation were found to be inhibited whereas an increase in SOD, CAT, GSH and FRAP was observed in the mice treated with EC prior to irradiation. Thus, pre-treatment with EC offers protection against γ-radiation induced hepatic alterations.     

Catalpol attenuates polycystic ovarian syndrome by regulating sirtuin 1 mediated NF-κB signaling pathway

Oxidative stress plays a central role in polycystic ovary syndrome (PCOS). Catalpol (CAT) is the active ingredient of Rehmannia glutinosa Libosch which has therapeutic effect on PCOS. However, little is known about the mechanism of CAT in PCOS. PCOS rats were induced by subcutaneous injection of dehydroepiandrosteronec for four weeks and then were treated with CAT (50 mg/kg) or carboxyl methyl cellulose (the solvent of CAT) or normal saline for another 4 weeks. Histopathological observation of ovarian tissues, the levels of testosterone, estradiol and progesterone in rat plasma samples, the oxidative stress related-indexes and the expressions of NF-κB pathway-related proteins were determined. KGN cell (human ovarian granulosa cell line) was used as PCOS cell model and was transfected with siSIRT1 in the presence of CAT. The viability, proliferation and apoptosis of cells and the levels of SIRT1 and NF-κB pathway-related proteins were measured. CAT lessened the anthropometric indices and improved ovarian damage in PCOS model rats, and reduced the levels of testosterone, estradiol, progesterone and MDA, increased GSH content, and elevated the activities of catalase, GSH-Px and SOD in ovarian tissues of PCOS model rats. CAT up-regulated SIRT1 level and inhibited the activation of NF-κB signaling pathway in PCOS rat model and KGN cells. Silencing SIRT1 increased the viability and proliferation, whilst decreased the apoptosis of CAT-treated KGN cells. Silencing SIRT1 counteracted the effect of CAT on the level of oxidative stress-related factors and NF-κB signaling pathway in KGN cells. CAT attenuated PCOS by regulating SIRT1 mediated NF-κB signaling pathway.     

Accumulation and oxidative stress biomarkers in Japanese flounder larvae and juveniles under chronic cadmium exposure

This study investigated how Cd exposure affected oxidative biomarkers in Japanese flounder, Paralichthys olivaceus, at early life stages (ELS). Fish were exposed to waterborne Cd (0–48 µg L^− 1) from embryonic to juvenile stages for 80 days. Growth, Cd accumulation, activities of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), glutathione S-transferase (GST, EC 2.5.1.18), and levels of glutathione (GSH) and lipid peroxidation (LPO) were investigated at three developmental stages. Flounder growth decreased and Cd accumulation increased with increasing Cd concentration. In metamorphosing larvae, CAT and SOD activities were inhibited and GSH level was elevated, while LPO was enhanced by increasing Cd concentrations. CAT and GST activities of settling larvae were inhibited but GSH level was elevated at high Cd concentrations. In juveniles, SOD activity and LPO level were increased but GST activity was inhibited as Cd concentration increased. Antioxidants in flounder at ELS were able to develop ductile responses to defend against oxidative stress, but LPO fatally occurred due to Cd exposure. These biochemical parameters could be used as effective oxidative biomarkers for evaluating Cd contamination and toxicity in marine environments: CAT, SOD, GSH, and LPO for metamorphosing stage; CAT, GSH, and GST for settling stage; and SOD, GST, and LPO for juvenile stage.     

Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury

Sub-acute hepatotoxicity was induced in mice by exposure to pesticides. The effect of pretreatment with aqueous black tea extract on lipid peroxidation and antioxidants in the liver was investigated. Administering a combination dose of chlorpyriphos and cypermethrin (20 mg kg(-1) each) on alternate days over a 15-day period to male mice resulted in induction of sub-acute toxicity as reflected by elevated levels of liver damage marker enzymes alkaline phosphatase(ALP), aspartate transaminase(AST) and alanine transaminase(ALT). Significantly elevated levels of lipid peroxidation were observed in the experimental group (group III) as compared with control mice. Decreased activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total thiol, glutathione peroxidase (GPx), glutathione reductase(GR) and glutathione-S-transferase (GST) were also observed in pesticide-treated as compared to control mice. Aqueous black tea extract was given as a pretreatment to group IV mice at a dose of 200 mg ml(-1) polyphenols before the pesticide dose, which significantly decreased the levels of lipid peroxidation and significantly elevated the activities of SOD, CAT, GSH, total thiol, GPx, GR and GST in liver to levels similar to the controls. Thus, the data offer support for the claim that the central mechanism of pesticide action occurs via changes in cellular oxidative status and shows conclusively that supplementation with black tea extract protects against the free radical-mediated oxidative stress in hepatocytes of animals with pesticide-induced liver injury.     

Promising role of ferulic acid,atorvastatin and their combination in ameliorating high fat diet-induced stress in mice

AimsThe present study evaluated a comparative and combined hepatoprotective effect of atorvastatin (AS) and ferulic acid (F) against high fat diet (HFD) induced oxidative stress in terms of hyperlipidemia, anti-oxidative status, lipid peroxidation and inflammation.Main methodsMale Swiss albino mice were given a diet containing high fat (H) (23.9% wt/wt), supplemented with AS (10 mg/kg) or F (100 mg/kg) and both (10 and 100 mg/kg) for 8 weeks. The control mice (C) were fed with normal diet.Key findingsThe H mice exhibited increased body weight; hyperlipidemia; serum level of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); hepatic lipid profile; lipid accumulation; reactive oxygen species (ROS) of hepatocytes, lipid peroxidation and liver antioxidant capacity was decreased. Immunofluorescent and Western blot assay revealed activation of nuclear factor kappa B (NF-κB) signaling pathway. The addition of F or AS and both in the diet significantly counteracted HFD induced body weight gain; hyperlipidemia; TNF-α, IL-6; hepatic lipid profile; fatty infiltration; NF-κB signaling pathway; ROS; lipid peroxidation and moreover elevated levels of hepatic antioxidant enzymes activity were observed.SignificanceSimultaneous treatment with AS, F and their combination protected against HFD induced weight gain and oxidative stress. The protection may be attributed to the hypolipidemic and free radical scavenging activity of AS or F and their combination. This study illustrates that AS and F have relatively similar hypolipidemic, antioxidative, anti-inflammatory actions and the AS + F combination along with HFD has shown outstanding effects as compared to other treated groups.     

Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals.     

Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity in hypercholesterolaemic rats

Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the people of south eastern (SE) region of Iran as a medicinal plant. This therapeutical application has been attributed to Nasturtium officinale (N. officinale) antioxidant capacity which is mostly tested by means of cell-free assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). In addition, the antioxidant effect of N. officinale extract has been investigated in hypercholesterolaemic rats in vivo. The results revealed that the extract has notable scavenging activity against DPPH radicals as well as potent reducing power in FRAP assay. Intragastric administration of N. officinale (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30 days lowered their blood total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively. However, the blood high density lipoprotein cholesterol (HDL-C) levels in the same treated rats increased by 16%. To evaluate the mechanism(s) of action, we studied the antioxidative potential of N. officinale extract in terms of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities and also the level of reduced glutathione (GSH) in the liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index of lipid peroxidation) was also determined. Under hypercholesterolaemic condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion along with significant reduction in the activities of CAT and SOD in rats fed high-fat diet rats. On the other hand, significant elevation in the activities of GPx and GR were seen in the same group of rats. Treatment of hypercholesterolaemic rats with N. officinale extract significantly increased the GSH level along with enhanced CAT and SOD activities in liver tissues. Furthermore, N. officinale extract significantly decreased hepatic MDA as well as GPx and GR activities in plant-treated rats. Based on our data, it can be concluded that N. officinale has a high hypolipidaemic activity and this may be attributed to its antioxidative potential.     

外源GSH对盐胁迫下番茄幼苗生长及抗逆生理指标的影响

采用营养液栽培法,研究外源谷胱甘肽(GSH)对NaCl胁迫下番茄幼苗生长、根系活力、电解质渗透率和丙二醛(MDA)、脯氨酸(Pro)、可溶性糖含量以及超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)活性的影响,为利用外源物质减轻盐胁迫伤害提供理论依据。结果显示:(1)NaCl胁迫显著抑制了番茄幼苗的生长、根系活力和SOD、POD、CAT活性,提高了电解质渗透率及MDA、Pro、可溶性糖含量;(2)外源喷施GSH能够诱导NaCl胁迫下番茄幼苗叶片抗氧化酶SOD、POD、CAT活性上调,电解质渗透率及MDA含量下降,Pro和可溶性糖含量恢复至对照水平;(3)外源喷施还原型谷胱甘肽抑制剂(BSO)使NaCl胁迫下番茄幼苗的根系活力以及抗氧化酶SOD、POD、CAT活性下降,脯氨酸含量提高;(4)喷施GSH可诱导BSO和NaCl共处理番茄植株的根系活力、SOD、POD、CAT活性提高,MDA和Pro含量降低。研究表明,外源GSH可通过提高促进盐胁迫下番茄幼苗植株渗透调节能力及清除活性氧的酶促系统的防御能力、降低细胞膜脂过氧化程度、保护膜结构的完整性,从而有效缓解NaCl胁迫对番茄幼苗生长的抑制,提高其耐盐性。     

Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice

Silymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30?mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.     

Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury

Aqueous extract (OE) of the leaves of Ocimum sanctum, the Indian holy basil, has been found to protect mouse against radiation lethality and chromosome damage and to possess significant antioxidant activity in vitro. Therefore a study was conducted to see if OE protects against radiation induced lipid peroxidation in liver and to determine the role, if any, of the inherent antioxidant system in radioprotection by OE. Adult Swiss mice were injected intraperitoneally (i.p.) with 10 mg/kg of OE for 5 consecutive days and exposed to 4.5 Gy of gamma radiation 30 min after the last injection. Glutathione (GSH) and the antioxidant enzymes glutathione transferase (GST), reductase (GSRx), peroxidase (GSPx) and superoxide dismutase (SOD), as well as lipid peroxide (LPx) activity were estimated in the liver at 15 min, 30 min, 1, 2, 4 and 8 hr post-treatment. LPx was also studied after treatment with a single dose of 50 mg/kg of OE with/without irradiation. OE itself increased the GSH and enzymes significantly above normal levels whereas radiation significantly reduced all the values. The maximum decline was at 30-60 min for GSH and related enzymes and at 2 hr for SOD. Pretreatment with the extract checked the radiation induced depletion of GSH and all the enzymes and maintained their levels within or above the control range. Radiation significantly increased the lipid peroxidation rate, reaching a maximum value at 2 hr after exposure (approximately 3.5 times that of control). OE pretreatment significantly (P < 0.0001) reduced the lipid peroxidation and accelerated recovery to normal levels. The results indicate that Ocimum extract protects against radiation induced lipid peroxidation and that GSH and the antioxidant enzymes appear to have an important role in the protection.     

Different susceptibility of prefrontal cortex and hippocampus to oxidative stress following chronic social isolation stress

Chronic oxidative stress plays an important role in depression. The aim of present study was to examine the stress-induced changes in serum corticosterone (CORT) levels, cytosolic protein carbonyl groups, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO) and total superoxide dismutase (SOD) activity in the prefrontal cortex versus hippocampus of male Wistar rats exposed to acute (2 h of immobilization or cold), chronic (21d of social isolation) stress, and their combination (chronic + acute stress). The subcellular distribution of nuclear factor-κB (NF-κB) and cytosolic cyclooxygenase 2 (COX-2) protein expressions were also examined. Depressive- and anxiety-like behaviors were assessed via the forced swim, sucrose preference, and marble burying tests in chronically isolated rats. Although both acute stressors resulted in elevated CORT, increased MDA in the prefrontal cortex and NF-κB activation accompanied by increased NO in the hippocampus were detected only following acute cold stress. Chronic isolation resulted in no change in CORT levels, but disabled appropriate response to novel acute stress and led to depressive- and anxiety-like behaviors. Increased oxidative/nitrosative stress markers, likely by NF-κB nuclear translocation and concomitant COX-2 upregulation, associated with decreased SOD activity and GSH levels, suggested the existence of oxidative stress in the prefrontal cortex. In contrast, hippocampus was less susceptible to oxidative damage showing only increase in protein carbonyl groups and depleted GSH. Taken together, the prefrontal cortex seems to be more sensitive to oxidative stress than the hippocampus following chronic isolation stress, which may be relevant for further research related to stress-induced depressive-like behavior.     

Quercetin attenuates lindane induced oxidative stress in wistar rats

A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (γ-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.     

Pomegranate reverses methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF-κB pathways

The clinical efficacy of the widely used chemotherapeutic drug methotrexate (MTX) is limited due to its associated hepatotoxicity. Pomegranate polyphenols are of huge health benefits and known to possess remarkable antioxidant properties capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. In this study, we explored the protective role of pomegranate fruit extract (PFE) in ameliorating MTX-induced hepatic damage. Male Swiss albino mice exposed to MTX (20 mg/kg body weight) exhibited distinct markers of toxicity such as increased activities of enzymes alanine transaminase, aspartate transaminase, lactate dehydrogenase and alkaline phosphatase and also increased oxidative stress in liver evidenced by increased ROS generation and lipid peroxidation. Decrease in reduced glutathione levels, superoxide dismutase, catalase, hepatic heme oxygenase 1 and NQO-1 activities were also observed. Tracing the signal transduction pathways, it was seen that MTX exposure significantly increased nuclear translocation of NF-κB coupled with increase in phosphorylated Iκ-B and down-regulation of NF-kappaB-dependent antiapoptotic protein Bcl-2. Treatment with MTX increased the expression of the apoptotic enhancer Rho/Cdc42 as well as the phosphorylation of SAPK/JNK. A shift in the Bax/Bcl-2 ratio towards apoptosis and increase in the caspase 3 level was also evident. Administration of PFE for 7 consecutive days before and after MTX challenge suppressed MTX-induced cell death, mitigated the injurious effects of MTX and offered protection against apoptosis. PFE was shown to reduce ROS generation in hepatocytes by activating the Nrf2-ARE pathway and inhibiting NF-κB as a consequence of which the antioxidant defense mechanism in the liver was up-regulated, thereby conferring protection against MTX-induced hepatotoxicity and apoptosis.     

Postharvest chilling induces oxidative stress response in the dwarf tomato cultivar Micro-Tom

Oxidative stress is involved in the response of Lycopersicon esculentum fruits (cultivar Micro-Tom) to chilling. Changes in activated oxygen scavenging enzymes, superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), ascorbate peroxidase (APX, EC 1.11.1.11), and glutathione reductase (GR, EC 1.6.4.2) were examined during ripening after postharvest chilling. Also, lipid peroxidation, respiration, and pigment contents were determined. These parameters were affected by chilling, especially the lycopene content and the respiration rate that showed a high value when the fruits were transferred to higher temperatures. CAT activity increased the day after the fruits were re-warmed, while the activity of GR was higher in the chilled than in the non-chilled green fruits. Lipid peroxidation was more evident at the 'pre-chilled' yellow and red fruits. APX and SOD were not affected by previous chilling in ripening fruits. These results indicate that oxidative stress is generated by conservation at 4°C. The antioxidant response of tomato fruit could be mediated by CAT and GR but not by SOD or APX. Moreover, CAT seemed to respond to the increase in the respiration rate.     

Oxidative stress biomarkers in the freshwater characid fish, Brycon cephalus, exposed to organophosphorus insecticide Folisuper 600 (methyl parathion)

Methyl parathion (MP) is an organophosphorus insecticide used worldwide in agriculture and aquaculture due to its high activity against a broad spectrum of insect pests. The effect of a single exposure to 2 mg L(- 1) of a commercial formulation of MP (MPc: Folisuper 600(R), MP 600 g L(- 1)) on catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) of the liver, white muscle and gills of Brycon cephalus was evaluated after 96 h of treatment. MPc exposure resulted in a significant induction of SOD, CAT and GST activity in all tissues. However, the GPx activity decreased significantly in white muscle and gills, whereas no alterations were observed in hepatic GPx activity. MPc also induced a significant increase in LPO values in the white muscle and gills, while hepatic LPO levels did not show any significant alteration. The current data suggest that MPc has oxidative-stress-inducing potential in fish, and that gills and white muscle are the most sensitive organs of B. cephalus, with poor antioxidant potentials. The various parameters studied in this investigation can also be used as biomarkers of exposure to MPc.     

Effects of genistein on early-stage cutaneous wound healing

Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-κB and TNF-α expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing.     

Suppression of NF-κB and NF-κB regulated oxidative stress and neuroinflammation by BAY 11-7082 (IκB phosphorylation inhibitor) in experimental diabetic neuropathy

Inflammation is an emerging patho-mechanism of diabetes and its complications. NF-κB pathway is one of the central machinery initiating and propagating inflammatory responses. The present study envisaged the involvement of NF-κB inflammatory cascade in the pathophysiology of diabetic neuropathy using BAY 11-7082, an IκB phosphorylation inhibitor. Streptozotocin was used to induce diabetes in Sprauge Dawley rats. BAY 11-7082 (1 &; 3 mg/kg) was administered to diabetic rats for 14 days starting from the end of six weeks post diabetic induction. Diabetic rats developed deficits in nerve functions and altered nociceptive parameters and also showed elevated expression of NF-κB (p65), IκB and p-IκB along with increased levels of IL-6 &; TNF-α and inducible enzymes (COX-2 and iNOS). Furthermore, there was an increase in oxidative stress and decrease in Nrf2/HO-1 expression. We observed that BAY 11-7082 alleviated abnormal sensory responses and deficits in nerve functions. BAY 11-7082 also ameliorated the increase in expression of NF-κB, IκB and p-IκB. BAY 11-7082 curbed down the levels of IL-6, TNF-α, COX-2 and iNOS in the sciatic nerve. Lowering of lipid peroxidation and improvement in GSH levels was also seen along with increased expression of Nrf2/HO-1. Thus it can be concluded that NF-κB expression and downstream expression of proinflammatory mediators are prominent features of nerve damage leading to inflammation and oxidative stress and BAY 11-7082 was able to ameliorate experimental diabetic neuropathy by modulating neuroinflammation and improving antioxidant defence.     

Salinity up-regulates the antioxidative system in root mitochondria and peroxisomes of the wild salt-tolerant tomato species Lycopersicon pennellii

The effect of salinity on the antioxidative system of root mitochondria and peroxisomes of a cultivated tomato Lycopersicon esculentum (Lem) and its wild salt-tolerant related species L. pennellii (Lpa) was studied. Salt stress induced oxidative stress in Lem mitochondria, as indicated by the increased levels of lipid peroxidation and H(2)O(2). These changes were associated with decreased activities of superoxide dismutase (SOD) and guaiacol peroxidases (POD) and contents of ascorbate (ASC) and glutathione (GSH). By contrast, in mitochondria of salt-treated Lpa plants both H(2)O(2) and lipid peroxidation levels decreased while the levels of ASC and GSH and activities of SOD, several isoforms of ascorbate peroxidase (APX), and POD increased. Similarly to mitochondria, peroxisomes isolated from roots of salt-treated Lpa plants exhibited also decreased levels of lipid peroxidation and H(2)O(2) and increased SOD, ascorbate peroxidase (APX), and catalase (CAT) activities. In spite of the fact that salt stress decreased activities of antioxidant enzymes in Lem peroxisome, oxidative stress was not evident in these organelles.