BERRY EXTRACTS IMPROVED INFLAMMATORY CYTOKINES, ANTIOXIDANT ENZYME AND SUPPRESSED THE GENE EXPRESSION ALTERATIONS IN DIABETIC RATS

Objective: The present work was conducted to evaluate the ameliorative effect of red berry (Morus rubra) and white berry (Morus alba) extracts in diabetic rats.Methods: Inflammatory biomarkers; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), paraoxanase1 (PON1), gene expression of apoptosis and inflammatory related genes were carried out.Results: Treatment of male rats with streptozotocin (STZ) to induce diabetes increased the levels of TNF-α, IL-1β, TGF-β, the apoptosis rates and the alterations of the pro-apoptosis (eotaxin, caspase-1, and caspase-2) and inflammation; nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB1) and allograft inflammatory factor 1 (AIF-1) related genes. While marked reduction in PON1 level was detected in STZ-induced diabetic rats. However, treatment of STZ-exposed rats with red and white berry extracts exhibited noticeable ameliorations in TNF-α, IL-1β, TGF-β levels and PON1 activity as well as low apoptosis rates and decreased the alteration of the pro-apoptosis and inflammatory related genes.Conclusion: Red and white berry extracts exhibited attenuation in antioxidant status, suppressed inflammatory cytokines, apoptosis and the alterations in the apoptosis and inflammatory related genes induced by STZ in male rats

ANTINEURODEGENERATIVE ACTIVITY OF MICROALGAE DUNALIELLA SALINA IN RATS WITH ALZHEIMER'S DISEASE

Objective: The present study is aimed to investigate the promising action of Dunaliella salina extract as a natural protector against Alzheimer's disease (AD) and reported to possess a variety of activities, including antioxidant effects due to its ability to create large amount of carotenoids.Methods: D. salina is a type of halophile green microalgae was used in the present study. 50 male rats were used in this study, where aluminum chloride was orally administered to induce AD in a dose of 100 mg/kg, daily for 6 weeks. Al-intoxicated rats treated orally daily with D. salina ethanolic extract for 6 weeks in a dose of 150 mg/kg b.wt., whereas standard anti-Alzheimer drug donepezil tartrate was administered at the dose of 10 mg/kg b.wt./day for 6 consecutive weeks. The anti-Alzheimer properties of D. salina extract were achieved through measuring the calmodulin (CaM) level, paraoxonase 1 (PON1) activity, the antiapoptotic marker (Bcl2), brain-derived neurotrophic factor (BDNF), the generation of the DNA adducts (8-hydroxy-2-deoxyguanosine [8-OHdG]/2-deoxy guanosine [2-dG]), and alteration in the expression of amyloid precursor protein, β-site APP-cleaving enzyme 1 (BACE1), and β-site APP-cleaving enzyme 2 (BACE2) in AD rats.Results: The current results demonstrated that supplementation of AD rats with D. salina extract-enhanced CaM level, and increased PON1 activity, upregulated Bcl2 and BDNF, decreased the levels of DNA adducts (8-OHdG/2-dG), and suppressed the alterations of the expression levels of APP, BACE1, and BACE2-m RNAs as compared with those in AD rats.Conclusion: It could be concluded that the biological activity of D. salina extract might be regulated by 9-cis b-carotene protecting the brain cells from the oxidative stress in AD rats.Keywords: Dunaliella salina, Calmodulin, Paraoxonase 1, Bcl2, Brain-derived neurotrophic factor, Alzheimer's disease, DNA adduct, Amyloid precursor protein

HAEMATOCOCCUS PLUVIALIS EXTRACT PROMOTING THE RECOVERY OF MEMORY IMPAIRMENT IN ALZHEIMER'S RATS: ANTI-INFLAMMATORY AND ANTIAPOPTOTIC EFFECTS

ABSTRACTObjective: The present study was conducted to investigate the role of Haematococcus pluvialis extract against oxidative damage, the inflammatory,and apoptotic impacts characterizing the neurodegenerative disorders.Methods: Oxidative stress, B-cell lymphoma 2, brain-derived neurotrophic factor, the inflammation, apoptotic and antiapoptotic impacts in Alzheimer'sdisease (AD) rats were determined through assessment of glutathione reduced (GSH), GSH peroxidase (GPx), lipid peroxide (malondialdehyde), thecytokines level such as tumor necrosis factor-alpha (TNF-α), interleukins (IL-6 and IL-1β), and macrophage inflammation protein (MIP1α) in AD rats.Moreover, the expression of phosphoinositide 3-kinase (PI3K) and serine-threonine protein kinase (Akt) genes regulating the apoptosis in AD ratswas measured.Results: The results revealed that levels of TNF-α, IL-6, IL-1β, and MIP1α were significantly increased in AD rats. Moreover, the expression of PI3Kand Akt genes was downregulated which it was coincided with the increase of apoptosis in AD rats. On the other hand, treatment of AD rats withH. pluvialis extract decreased the oxidative stress of AD in the form of prevention the inflammatory and apoptotic impacts.Conclusion: H. pluvialis could be used for ameliorating AD due to its role in decreases the oxidative stress of AD in the form of prevention theinflammatory and apoptotic impacts. H. pluvialis is a very attractive candidate for uses against neurodegenerative disorders that are caused byincreases oxidative stress inducing neuroinflammation and apoptosis.Keywords: Haematococcus pluvialis, Oxidative stress, Inflammation biomarkers, Apoptotic and antiapoptotic impacts

Zaštitno djelovanje selenija protiv prekomjerne ekspresije apoptotskih gena povezanih s karcinomom u štakora izloženih o-krezolu

Cresols are monomethyl derivatives of phenol frequently used as solvents and intermediates in the production of disinfectants, fragrances, pesticides, dyes, and explosives, which is probably why they are widely distributed in the environment. General population may be exposed to cresols mainly through inhalation of contaminated air. In this study we evaluated the toxicological effects of o-cresol on differential gene expression profile of rat liver and prostate. Experiments were conducted on 80 male rats, 60 of which were exposed to o-cresol (1.5 g kg-1, 5 g kg-1, or 15 g kg-1) through feed for 8 weeks. Three groups of rats were supplemented with 0.1 mg kg-1 selenium (Se, in the form of, sodium selenite) in addition to o-cresol to evaluate its effectiveness against o-cresol toxicity. Control group received neither o-cresol nor Se, while one group received Se alone. Survival was similar between the exposed and control animals. Rats exposed to 15 g kg-1 of o-cresol showed a 16 % loss in body weight by the end of the study, which may have been related to o-cresol making feed unpalatable at this concentration. Liver and prostate tissue samples were collected at the end of the treatment. mRNA analysis revealed that apoptotic genes (CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1, and PKCα) related to cancer were up-regulated in liver and prostate tissues isolated from groups exposed to 5 g kg-1 and 15 g kg-1 o-cresol in comparison to control. Changes in gene expression profile were prevented when rats were supplemented with Se. The exact mechanisms underlying its protective effect remain to be clarified by future studies.Krezoli su monometilni derivati fenola koji se često rabe kao otapala te kao posrednici u proizvodnji dezinfekcijskih sredstava, mirisa, pesticida, boja i eksploziva. Otuda i njihova rasprostranjenost u okolišu. Opća je populacija izložena krezolima uglavnom putem zraka. U ovome se toksikološkom istraživanju ocijenilo djelovanje o-krezola, jednoga od tri krezolova izomera, na ekspresiju gena u tkivima jetre i prostate mužjaka štakora. Istraživanje je provedeno na 80 mužjaka, od kojih je 60 tijekom osam tjedana bilo izloženo o-krezolu (1,5 g kg-1, 5 g kg-1, odnosno 15 g kg-1) preko krmiva. Tri skupine štakora primale su uz o-krezol nadomjestak selenija u dozi od 0.1 mg kg-1 (Se, u obliku natrijeva selenita) radi ocjene njegove djelotvornosti protiv toksičnosti o-krezola. Kontrolna skupina nije primala ni o-krezol ni Se, dok je jedna skupina primala samo Se. Preživljenje je bilo podjednako u svih skupina životinja. Štakori izloženi najvišoj dozi o-krezola (15 g kg-1) imali su 16 % manju tjelesnu masu od kontrolne skupine na kraju ispitivanja, što može biti povezano s lošim okusom krmiva zbog primjese visoke doze o-krezola. S istekom osmotjednoga izlaganja o-krezolu životinje su eutanazirane te su prikupljeni uzorci tkiva jetre i prostate. Analiza m-RNA pokazala je značajno povišenu ekspresiju apoptotskih gena CYP3A, COX-2, PPARγ, BAX, BCL2, AKT-1 i PKCα, koji su povezani s nastankom karcinoma u skupinama štakora izloženim o-krezolu (5 g kg-1 i 15 g kg-1 u odnosu na kontrolu. Ova je prekomjerna ekspresija poništena u štakora koji su primali selenij. Još nisu jasni mehanizmi iza ovoga zaštitnog djelovanja, na što će odgovoriti buduća istraživanja

Effect of natural PAL-enzyme on the quality of egg white and mushroom flour and study its impact on the expression of PKU related genes and phenylalanine reduction in mice fed on

PKU patients react to therapy with a low phenylalanine diet, but adherence to this diet is troublesome, subsequently the expansion of alternative ways is demand. Phenylalanine ammonia lyase (PAL) is one of this ways, which converts phenylalanine to harmless metabolites; trans-cinnamic acid and ammonia. In the current study, the extraction of PAL enzyme was used to investigate the efficiency for production of functional PKU egg white and mushroom flour with good quality by evaluation of colour characteristics, determination of phenylalanine concentrations and genetic materials expression of PKU related genes and DNA damage. Results indicated that the PAL enzyme treated of egg white and mushroom flour was stable colour and the calculated reduction per cent in phenylalanine concentration from female mice fed on untreated and PAL–treated samples was 22.77% in egg white and 31.37% in mushroom flour. Also, the results revealed that female mice fed on diet contained treated egg white exhibited low expression levels of PKU exons (3, 6, 7, 11, and 12) and low DNA damage which were similar to those in control mice