Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis.

Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1ß), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-α (TNF-α), Caspase-3, 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1ß, iNOS, TNF-α, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67-fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.

Phytochemical Profiling and Biological Activity of Achillea sintenisii Hub.-Mor.

Achillea (Asteraceae) species have been traditionally used for their different therapeutical properties. In this study, phytochemical composition of aerial parts of A. sintenisii which is endemic in Turkey was determined with Liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). To evaluate the wound healing potential, the cream formulation prepared from A. sintenisii was tested on the linear incision wound model in mice. In vitro enzyme inhibitory activity tests were performed on elastase, hyaluronidase, and collagenase. In the histopathological examination, angiogenesis and granulation tissue formation were significantly increased in A. sintenisii treatment groups compared to the negative control group. As a result of this study, it is thought that the enzyme inhibition and antioxidant activity of the plant may contribute to the wound healing process. According to LC/MS/MS analysis result, quinic acid (24.261 µg/mg extract) and chlorogenic acid (14.97 µg/mg extract) were identified as main constituents of the extract.

Marine Phytoplankton Improves Exercise Recovery in Humans and Activates Repair Mechanisms in Rats.

This study investigated the effects of marine phytoplankton supplementation on 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. In the human trial, a 5-week resistance-training program with intentional overreaching on weeks 2 and 5 was implemented. Results indicate that marine phytoplankton prompted positive changes in perceived recovery at post-testing and, while both marine phytoplankton and placebo conditions demonstrated decreased peak and mean rate of force development following the overreaching weeks, placebo remained decreased at post-testing while marine phytoplankton returned to baseline levels. In the rat model, rats were divided into four conditions: (i) control, (ii) exercise, (iii) exercise + marine phytoplankton 2.55 mg·d-1, or (iv) exercise+marine phytoplankton 5.1 mg·d-1. Rats in exercising conditions performed treadmill exercise 5 d·wk-1 for 6 weeks. Marine phytoplankton in exercising rats increased positive and decrease negative myogenic factors regulating satellite cell proliferation. Taken together, marine phytoplankton improved perceptual and functional indices of exercise recovery in an overreaching human model and, mechanistically, this could be driven through cell cycle regulation and a potential to improve protein turnover.

Allyl isothiocyanate attenuates LED light-induced retinal damage in rats: exploration for the potential molecular mechanisms.

PURPOSE: Environmental light pollution due to artificial light may increase the rate and severity of retinal diseases, and plant-based nutritional interventions with antioxidant properties have the potential to reverse this phenomenon. We aimed to investigate the potential effects of allyl isothiocyanate (AITC) against white light-emitting diode (LED)-induced retinal degeneration (RD) in the rats. METHODS: Twenty-eight male rats were allocated as: (i) Control, (ii) LED, (iii) LED + AITC (10 mg/kg BW), (iv) LED + AITC (20 mg/kg BW). Rats were administered with AITC for 28 days, followed by two days of intense environmental LED light (750 Lux) exposure to the eyes. Animals were sacrificed immediately at the end of the study, then the blood and eyeballs were taken for the biochemical, western blotting, and histopathology examinations. RESULTS: AITC lowered the serum and retina malondialdehyde (MDA) levels while significantly (p < 0.05) improving the retinal antioxidant enzyme activities in a dose-dependent manner. AITC improved retinal and outer nuclear layer (ONL) thickness as compared to the LED group (p < 0.05). AITC increased the levels of Bax, caspase-3, HO-1, GAP43, and VEGF, while decreasing IL-1ß, IL-6, NF-κB, Bcl-2, GFAP, Grp78, activating ATF4 and ATF6 as compared to the LED group (p < 0.05). CONCLUSION: In conclusion, four weeks of AITC administration to the rats showed specific protective effects against two days of intense LED light-induced retinal damage; through antiinflammatory, antioxidant, anti-apoptotic, and modulating mitochondrial metabolic pathways.

Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

Background/aim: This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats. Materials and methods: Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results: Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group. Conclusion: These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.

Effects of taurine supplementation on productive performance, nutrient digestibility and gene expression of nutrient transporters in quails reared under heat stress.

This study was conducted to examine the effects of dietary taurine supplementation on productive performance, nutrient digestibility, antioxidant status, and the gene expression of ileal nutrient transporters in laying quails reared under heat stress (HS). One hundred and eighty laying Japanese quails (Coturnix coturnix japonica) were fed a basal diet or basal diet supplemented with either 2.5 or 5 g of taurine per kg of diet, and reared at either 22 ± 2 °C for 24 h/d (thermoneutral, TN) or 34 ± 2 °C for 8 h/d (HS) for 12 weeks. The quails reared under HS consumed less feed, produced less egg, and had lower dry matter, organic matter and crude protein apparent digestibilities compared with the quails reared under the TN condition (P = 0.001). However, increasing taurine concentrations in the diet improved feed intake and egg production (P = 0.001), but also the apparent digestibilities (P ≤ 0.027) in quails reared under HS. The greater doses (5 g/kg) of taurine resulted in more responses. The quails reared under HS had greater serum and liver MDA concentrations (P = 0.0001) which decreased with dietary taurine supplementations, particularly greater doses. The gene expressions of ileal PEPT1, EAAT3, CAT1, CAT2, SGLT1, SGLT5, GLUT2, and GLUT5 decreased under HS conditions (P = 0.001). However, supplementing taurine, in a dose-dependent fashion, to the diet of quails reared under HS resulted in increases in the gene expressions of the transporters (P < 0.05) except for CAT1. The results of the present work showed that taurine supplementation, particularly with greater doses (5 g/kg), to the diet of laying quails kept under HS acts as alleviating negative effects of HS, resulting in improvements in productive performance and nutrient digestion, and also upregulation of ileal nutrient transporters.

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis. Materials and methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund's adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed. Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws. Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.

Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats.

BACKGROUND: Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. METHODS: Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-κB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. RESULTS: L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-κB and GFAP levels were decreased by administration of L/Zi. CONCLUSIONS: According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress.

Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice.

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1ß (IL1ß) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.

Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high-fat diet/streptozotocin-induced type 2 diabetes mellitus in rats.

Allyl isothiocyanate (AITC), a dietary phytochemical found in some cruciferous vegetables, is commonly used as an antimicrobial, anticancer, and antioxidant agent. In the present study, we investigated the effects of AITC on insulin resistance and transcription factors in a diabetic rat model. A total of 42 Wistar rats were divided into six groups and orally treated for 12 weeks as follows: (i) control; (ii) AITC (100 mg/kg body weight [BW]); (iii) high fat diet (HFD); (iv) HFD + AITC (100 mg/kg BW); (v) HFD + streptozotocin (STZ, 40 mg/kg BW); and (vi) HFD + STZ + AITC. Administration of AITC reduced blood glucose, total cholesterol, triglycerides, and creatinine levels, but increased (P < 0.001) total antioxidant capacity. In AITC-treated rats, the glucose transporter-2, peroxisome proliferator-activated receptor gamma, p-insulin receptor substrate-1, and nuclear factor erythroid-derived 2 in the liver and kidney were increased while nuclear factor-kappa B was downregulated (P < 0.05). In conclusion, AITC possesses antidiabetic, antioxidant, and anti-inflammatory activities in HFD/STZ-induced T2DM in rats. These findings may further justify the importance of AITC in phytomedicine.

Evaluation of antioxidant and antiproliferative activities of 1,2-bis (p-amino-phenoxy) ethane derivative Schiff bases and metal complexes.

In this study, the effects of the two Schiff base derivatives and their metal complexes were tested for MDA concentration, which is an indicator of lipid peroxidation, antioxidant vitamin A, vitamin E, and vitamin C levels in cell culture. A comparison was performed among the groups and it was observed that MDA, vitamin A, vitamin E, and vitamin C concentrations were statistically changed. According to the results, all compounds caused a significant oxidative stress without Zn complexes. Moreover, Mn(II), Cu(II), Zn(II), and Ni(II) complexes of Schiff bases derived from a condensation of 1,2-bis (p-aminophenoxy) ethane with naphthaldehydes and 4-methoxy benzaldehyde were examined in terms of antitumor activity against MCF-7 human breast cancer and L1210 murine leukemia cells. Furthermore, the derivatives were tested for antioxidative and prooxidative effects on MCF-7 breast cancer cells. The compounds which were tested revealed that there was an antitumor activity for MCF-7 and L 1210 cancer cells. Also, some of the compounds induced oxidative harmful.

(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers.

PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. RESULTS: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), Gα Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-κB (NF- κB) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. CONCLUSIONS: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.

Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of Mice by ATP-Sensitive Potassium Channels.

Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (KATP) in stellate cells of the ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue. The specific and clearly visible bands for all subunits but that for Kir6.1 were seen in Western blot. Using immunohistochemical staining technique, stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1 were too weak. In patch clamp recordings, KATP agonists including cromakalim (50 µM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5-nitro pyridine) (DTNP) (330 µM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 µM), 6-chloro-3-(methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414) (1 µM), and H2O2 (0.88 mM) induced marked responses in stellate cells, characterized by membrane hyperpolarization which were blocked by KATP antagonists. Blockers of KATP channels, glibenclamide (0.2 mM), tolbutamide (0.1 mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused depolarization of stellate cells, increasing spontaneous action potential firing. In conclusion, KATP channels seemed to be composed dominantly of Kir 6.2 subunit and SUR1 and SUR2 and activation or inhibition of KATP channels regulates firing properties of stellate cells by means of influencing resting membrane potential and input resistance.

LFM-A13, a potent inhibitor of polo-like kinase, inhibits breast carcinogenesis by suppressing proliferation activity and inducing apoptosis in breast tumors of mice.

The goals of the present study were to define the anticancer activity of LFM-A13 (α-cyano-ß-hydroxy-ß-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A13 treatment upregulated the levels of IκB, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.

L-Carnitine supplementation increases expression of PPAR-γ and glucose transporters in skeletal muscle of chronically and acutely exercised rats.

In this study, the effects of L-Carnitine supplementation on the lipid peroxidation and expression of PPAR-γ and glucose transporters in the liver and muscles of chronically and acutely exercised rats were investigated. A total of 42 male Wistar Albino rats (8-week-old) were divided into six groups as follows: Control, L-Carnitine, Chronic Exercise (CE), Chronic Exercise + L-Carnitine, Acute Exercise (AE) and L-Carnitine + Acute Exercise. Chronic exercise consists of 30 m/min, 30 min/day, and 5 days/week for 6 weeks. Rats in the acute exercise groups were run on the treadmill at 30 m/min until exhaustion. L-Carnitine was given at the level of 300 mg per kilogram of diet for 6 weeks. There was no significant difference in the levels of serum ALT, AST, urea, creatinine and glucose levels between the exercise and L-Carnitine groups (P > 0.05). Cholesterol and triglyceride levels decreased by L- carnitine supplementation and chronic exercise in control groups but increased in the AE groups compared to the control group without reinforcement (P < 0.05). Serum, muscle, heart, and liver malondialdehyde (MDA) concentrations were lower in CE and higher in the AE groups (P < 0.001). However, L-Carnitine supplementation reduced MDA levels (P < 0.05). Liver and muscle PPAR-γ, liver GLUT-2 and muscle GLUT-4 mRNA expressions were lower in AE group than in all other groups (P < 0.001). Both chronic exercise and supplemental L-Carnitine increased liver and muscle PPAR-γ, GLUT-2 and GLUT-4 mRNA expression (P <0.05). As a result, although acute exercise increased oxidative stress, chronic exercise reduced oxidative stress by lowering lipid peroxidation level. L-Carnitine supplementation decreased oxidative stress and improved glucose and lipid metabolism by regulation of PPAR-γ, GLUT-2 and GLUT-4 mRNA expression in rats.

Lutein and zeaxanthin isomers modulates lipid metabolism and the inflammatory state of retina in obesity-induced high-fat diet rodent model.

BACKGROUND: Several studies associated high-fat intakes with a high incidence of age-related macular degeneration (AMD). Lutein and Zeaxanthin isomers (L/Zi) may counteract reactive oxygen species produced by oxidative stress. The present study was conducted to determine the possible effects of L/Zi administration on lipid profile, protein genes associated with oxidative stress and inflammation pathways in the obesity induced by a high-fat diet (HFD) in rodents. METHODS: Twenty-eight male Wistar rats were allocated into four groups as follows: (i) Control, (ii) Control + L/Zi, (iii) High Fat Diet (HFD), and (iv) HFD+ L/Z. L/Zi was administrated for 8 weeks at a daily dose of 100 mg/kg BW. RESULTS: L/Zi administration significantly reduced insulin and free fatty acid (FFA) levels (P < 0.001) and ameliorated the oxidative damage by reducing malondialdehyde (MDA) concentration and increasing antioxidant enzymes activities of retina induced by HFD. In addition, supplementation decreased the levels of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM) (P < 0.001, respectively) and improved nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) gene proteins in retinal tissues (P < 0.001). CONCLUSION: Rats fed with HFD exhibited increased oxidative stress and upregulation of inflammatory indicators. However, L/Zi supplementation modulates genes involved oxidative stress and inflammation including NF-κB and Nrf2 signaling pathways in the retina which may contribute to ameliorating retinal damage induced by HFD.

Schiff Base-Poloxamer P85 Combination Prevents Prostate Cancer Progression in C57/Bl6 Mice.

BACKGROUND: Prostate cancer which is the second most common cause of death among men has a high incidence in recent years. Current therapeutic regimens should be improved to overcome drug resistance. At the metastatic stage, tumors become refractory to established chemotherapeutic treatments and cause serious problems at the clinics. Development of new drug molecules that are able to transport through the membrane easily and kill tumor cells rapidly is of great interest. METHOD: In the current study, a novel Heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used for prostate cancer treatment in vivo. Tramp-C1 cells injected animals were subjected to chemotherapeutic formulation treatment and results were analyzed by toxicology analysis, tumor volume measurements, and histopathological analysis. 0.5 mg/kg Schiff base was selected and combined with 0.05% P85 according to the toxicology analysis showing the enzyme levels, blood parameters, and multiple organ toxicity. RESULTS: Results demonstrated that Heterodinuclear copper(II)Mn(II) complex-P85 combination decreased tumor formation and tumor volume steadily over the course of experiments. CONCLUSIONS: Overall, Heterodinuclear copper(II)Mn(II) complex-P85 exerted remarkable anti-cancer activity in vivo in C57/B16 mice. Prostate 76:1454-1463, 2016. © 2016 Wiley Periodicals, Inc.

Comparative evaluation of the sexual functions and NF-κB and Nrf2 pathways of some aphrodisiac herbal extracts in male rats.

BACKGROUND: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-κB, Nrf2, and HO-1 in reproductive tissues. METHODS: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. RESULTS: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-κB and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. CONCLUSIONS: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf2/ HO-1 pathway while inhibiting the NF-κB levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract. Schematic representation of the mode of action of some aphrodisiac herbal extracts to improve sexual functions.

Coenzyme Q10 Supplementation Modulates NFκB and Nrf2 Pathways in Exercise Training.

This study reports the effects of Q10, coenzyme Q10 or ubiquinone, a component of the electron transport chain in mitochondria, on nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), inhibitors of kappa B (IκB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and hemeoxygenase 1 (HO-1) in rats after chronic exercise training for 6 weeks. 8-week old male Wistar rats were assigned randomly to one of four treatments planned in a 2 x 2 factorial arrangement of two condition (sedentary vs. exercise training), and two coenzyme Q10 levels (0 and 300 mg/kg per day for 6 weeks). The expression levels of the target proteins were determined in the heart, liver and muscle, and biochemical parameters including creatinine, urea, glucose and lipid profile were investigated in plasma. When compared with sedentary group, significant decreases in heart, liver and muscle NFκB levels by 45%, 26% and 44% were observed in Q10 supplemented rats after exercise training, respectively, while the inhibitory protein IκB increased by 179%, 111% and 127% in heart, liver and muscle tissues. Q10 supplementation caused an increase in Nrf2 (167%, 165% and 90%) and HO-1 (107%, 156% and 114%) after exercise training in heart, liver and muscle tissues (p < 0.05). No significant change was observed in any of the parameters associated with protein, carbohydrate and lipid metabolism, except that exercise caused a decrease in plasma triglyceride, which was further decreased by Q10. In conclusion, these results suggest that Q10 modulates the expression of NFκB, IκB, Nrf2 and HO-1 in exercise training, indicating an anti-inflammatory effect of Q10 and emphasizes its role in antioxidant defense. Key pointsCoenzyme Q10 is a component of the electron transport chain in mitochondria which is linked to the generation of energy in the cell.Coenzyme Q10 may inhibit the peroxidation of lipids, thus acting as an antioxidant and protects tissue against oxidative injury.Using of coenzyme Q10 can significantly elevate IκB, Nrf2 and HO-1 and reduce NFκB during exercise training.

A Schiff base derivative for effective treatment of diethylnitrosamine-induced liver cancer in vivo.

Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.