THE PROTECTIVE EFFECT OF THYMOQUINONE AGAINST LEAD ACETATE INDUCED DNA DAMAGE AND ALTERATIONS IN TUMOR INITIATION GENES

objective: Several pollutants represent a significant ecological and public health concern due to their toxicity and their ability to accumulate in livingorganisms in which lead is one of them. The present investigation was designated to assess the modulating effect of thymoquinone (TQ) against leadacetate (LA) toxicity.Methods: Several endpoints were considered to design this study such as: The gene expression of tumor initiation genes (cytochrome P450 3A[CYP3A], cyclooxygenase 2 [COX2], BAX and Bcl), DNA damage and alterations in the levels of glutathione (GSH), lipid oxidation (malondialdehyde[MDA]), and protein oxidation (protein carbonyl [PC]) in male rats. About 60 male rats were used in this study which allocated in six groups (10 animaleach) and treated with LA (200 mg/kg diet), TQ (5 and 10 mg/kg b.wt.), and LA + TQ.2Results: The results revealed that LA induced significant DNA damage and alteration in the expression of CYP3A, COX2, BAX, and Bcl as well asinduced changes in GSH content and MDA and PC levels in male rats. Meanwhile, TQ was decreased significantly the toxic effect of LA in male ratswhich decreased the alterations in the gene expression and DNA damage as well as GSH content and MDA and PC levels.Conclusion: The results suggested that TQ treatment confers protection against toxicity inflicted by LA and support the contention that TQ protectionis achieved by its ability as a scavenger for free radicals generated by LA.Keywords: Thymoquinone, Lead acetate, Gene expression, DNA damage, 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

EXPERIMENTAL EVIDENCES FOR THE PROMISING HERAPEUTIC ROLE OF VITIS VINIFERA SEED EXTRACT AGAINST NONALCOHOLIC STEATOHEPATITIS

Objective: The present study was planned to investigate the possible therapeutic effect of methanolic extract of Vitis vinifera seeds on high fat diet-induced nonalcoholic steatohepatitis (NASH) in forty adult female Wistar rats.Methods: The animals were divided into four groups, (G1)was served as healthy control group and the other three groups received high fat diet for 32 weeks for induction of NASH were assigned as follow: (G2) in which the animals bearing NASH were left untreated, (G3) in which the animals bearing NASH were treated with Vitis vinifera seed extract in a dose of 0.28g/kg b. wt (GSH) and (G4) in which the animals bearing NASH were treated with Vitis vinifera seed extract in a dose of 0.14g/kg b. wt (GSL).Results: The results revealed significant increase in serum ALT activity, plasma glucose, insulin levels, serum resist in, NF-κB, TNF-α, HGF levels, hepatic TNF-α and HGF gene expression levels. While, serum albumin, adiponectin levels and hepatic adiponectin gene expression level were decreased significantly in NASH group. Conversely, treatment of NASH groups with GSH or GSL resulted in significant decrease in serum ALT activity, plasma glucose, insulin levels, serum resist in, NF-κB, TNF-α, HGF levels, hepatic TNF-α and HGF gene expression levels. However, serum albumin, adiponectin levels and hepatic adiponectin gene expression level were increased significantly as a consequence of treatment with GSH or GSL.Conclusions: The efficacy of Vitis vinifera extract against NASH might be attributed to its strong hepatoprotective potential and powerful anti-inflammatory activity in addition to its potent role in ameliorating insulin resistance indices.Â

POTENTIAL ROLE OF HAEMATOCOCCUS PLUVIALIS AGAINST DIABETES INDUCED OXIDATIVE STRESS AND INFLAMMATION IN RATS

Objective: The aim of this study is to investigate the impact of Haematococcus pluvialis extract against oxidative stress and inflammatory cytokines induced by hyperglycemia in diabetic rats.Methods: Oxidative stress; lipid peroxide (as presented by Malondialdehyde; MDA) and nitric oxide (NO), beside total antioxidant capacity, enzymatic and non-enzymatic antioxidants including reduced glutathione, glutathione peroxidase, and glutathione reductase were evaluated. The inflammatory cytokines; tumor necrosis factor-alpha and interleukin-1 beta were also investigated in rats' serum. Several analyses including expression of antioxidant enzyme related genes, reactive oxygen species (ROS) formation and DNA adducts were performed.Results: The results showed that diabetes mellitus induced-rats exhibited increase in oxidative stress biomarkers and inflammatory cytokines, lower expression levels of the antioxidant enzyme genes; superoxide dismutase and glutathione S-transferase than those in control rats. In addition, diabetic rats exhibited significantly higher levels of ROS generation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation. In contrary, supplementation of diabetic rats with H. pluvialis extract improved the negative effect of the hyperglycemia on antioxidant enzymes, the gene expression of antioxidant enzymes, and ROS generation as well as 8-OHdG formation.Conclusion: H. pluvialis extract decreased the oxidative stress, enhanced antioxidant status and inflammatory cytokines induced by hyperglycemia in diabetic rats. The effect of H. pluvialis extract involved in the increase of expression levels of antioxidant enzyme genes; decreased the levels of ROS generation and 8-OHdG formation which may be attributed to the presence of astaxanthin in H. pluvialis extract.Keywords: Haematococcus pluvialis, Hyperglycemia, Diabetes mellitus, Oxidative stress, Inflammatory cytokines, DNA adducts