Kadry M. Sadek

Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model

The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG.

The chemo-prophylactic efficacy of an ethanol Moringa oleifera leaf extract against hepatocellular carcinoma in rats

Abstract Context: Hepatocellular carcinoma (HCC) is among the most well-known threatening tumours around the world, and the outlook remains bleak. Moringa oleifera Lam. (Moringaceae) exhibits antitumor, antioxidant and hepatoprotective properties. Objectives: To assess the chemo-prophylactic proficiency and other likely activities of Moringa oleifera leaf ethanol extract (MOLEE) against diethyl nitrosamine (DEN)-induced HCC. Materials and methods: Wistar rats were gastrogavaged with MOLEE (500 mg/kg) for one week and then gastrogavaged with MOLEE and DEN (10 mg/kg) for the following 16 weeks. The progressions of the histological components, serum biomarkers and oxidation of DNA of the liver tissues were resolved to assess the prophylactic impacts. The lipid oxidative biomarker, the cancer prevention agent status and apoptotic proteins were surveyed to assess the potential mechanisms. Results: The MOLEE LD50 was estimated to be 5585 mg/kg. MOLEE (500 mg/kg) administration fundamentally repressed the expansion event of knobs and the normal knob number per knob-bearing livers prompted by DEN, enhanced hepatocellular appearance and altogether significantly decreased (p < 0.05) DEN-induced elevations in serum biochemical records and hepatic 8-hydroxy-2-deoxyguanosine (8-OHdG) levels by 29%. The robotic studies found that MOLEE disrupted the DEN-activated oxidative reactivity damage in rats by 46.8%. Curiously, the expression of Bcl-2, Bcl-xl and β-arrestin-2 were fundamentally diminished (p < 0.05); however, the expression of Bax and caspase-3 were essentially (p < 0.05) upregulated. Discussion and conclusions: The outcomes presume that MOLEE inspired critical defensive impacts against DEN-induced hepatocarcinogenesis that might be identified with the implementation of antioxidant activity and actuation of apoptosis.

Selective, reliable blood and milk bio-markers for diagnosing clinical and subclinical bovine mastitis

Mastitis is positioned as the most vital ailment in dairy cows in light of conventional cost examinations. The aim of the present study was to evaluate the diagnostic value of different acute phase proteins (APPs), pro-inflammatory cytokines, and oxidative stress biomarkers in healthy cows and in those with clinical or subclinical mastitis and to localize APP gene expression in the milk of mastitic cows. Therefore, 20 subclinical mastitic cows with positive California Mastitis Test (CMT) results and no clinical signs of mastitis, 15 clinically mastitic cows, and 15 healthy cows with negative CMT results and somatic cell count (SCC) of <600,000 cells/mL were selected. Milk and blood samples were collected. The present findings indicate that the biochemical parameters examined were significantly (p < 0.05) increased in cows with both types of mastitis, except for total protein, albumin, and GSH levels and the TAC, which were significantly (p < 0.05) decreased, compared with values in the controls. Surprisingly, SAA and Hp gene expression were up-regulated in milk from cows with both forms of mastitis, while Fb expression was absent. The present study demonstrates that APPs, pro-inflammatory cytokines, and indicators of oxidative stress may serve as biomarkers of clinical and subclinical mastitis. Interestingly, the expression of SAA and Hp indicates the local de novo synthesis of these APPs within the mammary glands. Furthermore, the presence of SAA and Hp transcripts in milk cells derived from pathogen-free mammary glands proved their constitutive expression. However, future studies with more extensive baseline sampling are still needed to establish and validate the reference values for APPs, cytokines, and oxidative stress markers in cows.

Melatonin mitigates thioacetamide-induced hepatic fibrosis via antioxidant activity and modulation of proinflammatory cytokines and fibrogenic genes

Aims: The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored. Main methods: Rats were allocated into four groups: placebo; thioacetamide (TAA) (200 mg/kg bwt, i.p twice weekly for two months); melatonin (5 mg/kg bwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor‐&agr;, and interleukin‐1&bgr;), fibrogenic‐related genes (transforming growth factor‐1&bgr;, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant‐related gene (thioredoxin‐1) were detected by qRT‐PCR. Key findings: In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s‐transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase‐1 (PON‐1), while inducing the accumulation of malondialdehyde, protein carbonyl (C = O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin‐1 mRNA transcripts. Significance: Melatonin exhibits potent anti‐inflammatory, antioxidant and fibrosuppressive activities against TAA‐induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin‐1 with attenuation of autotaxin expressions.

Spirulina platensis prevents hyperglycemia in rats by modulating gluconeogenesis and apoptosis via modification of oxidative stress and MAPK-pathways.

Spirulina platensis (SP) is a microalga with antioxidant, antidiabetic and anti-inflammatory properties. The present study explored the ability and potential mechanism(s) by which SP induced glucose lowering impact in diabetic rat model. Forty rats were allocated into four groups: control; streptozotocin (STZ)-induced diabetes (STZ, 45mg/kg b.w., intraperitoneally); SP (500mg/kg b.w., orally twice weekly for 2 months) and STZ-induced diabetes+SP group. In the STZ-induced diabetic rats, SP significantly decreased (P>0.05) serum glucose, glycated hemoglobin (HbA1c), malondialdehyde (MDA) levels and significantly increased (P>0.05) serum insulin, the activity of antioxidant enzymes and normalized their mRNA gene expression. Furthermore, SP attenuates STZ-induced upregulation of the gluconeogenic enzyme pyruvate carboxylase (PC), the pro-apoptotic Bax and caspase-3 (CASP-3), tumor necrosis factor alpha (TNF-α) gene expression. The Western blot results revealed that, SP induced downregulation of mitogen activated protein kinase pathway (MAPK) protein expression in hepatic tissues of diabetic rats. Additionally, SP reestablished the typical histological structure of the liver and pancreas of diabetic rats. Acute toxicity study further shows that SP is relatively safe. This study demonstrates that SP is rich in antioxidant compounds and has powerful glucose lowering effect through the normalization of increased hepatic PC gene expression. Interestingly, SP induced recovery of damaged hepatocytes and pancreatic β-cells via its anti-inflammatory, antioxidant and anti-apoptotic properties. The MAPK signaling cascade is a pivotal component of the proapoptotic signaling pathway induced by diabetes mellitus. MAPK activation may be dependent from ROS production, since SP which exhibited antioxidant activities did have a significant impact on MAPK activity.

Role of lncRNAs as prognostic markers of hepatic cancer and potential therapeutic targeting by S-adenosylmethionine via inhibiting PI3K/Akt signaling pathways

Hepatic cancer (HCC) is a well-identified dilemma throughout the world, and hence, the molecular mechanisms and strategy for preventive protection against this malignancy are critical. S-adenosylmethionine (SAM) is a unique methyl granter in vast reactions, including DNA methylation, and secures the genome against hypomethylation, which is a hallmark of tumors. Consequently, SAM may control the rate of gene expression. The objective of this investigation was to evaluate the expression of long noncoding RNAs (lncRNAs) transcript involved in hepatic tumorigenesis, including additional coding CEBPA (ecCEBPA) and urothelial carcinoma related 1 (UCA1), antioxidant enzymes transcripts, and relevant signaling pathway in diethylnitrosamine (DEN)-prompted HCC along with their conceivable targeting by SAM at different stages of HCC in rats. Our outcomes revealed that SAM particularly when given at the starting phase downregulates ecCEBPA and UCA1 gene transcripts and ameliorate histopathological alterations in DEN-initiated HCC. Interestingly, SAM attenuates DEN-induced upregulation of PI3K/Akt protein expression. However, SAM upregulates the antioxidant enzymes mRNA transcripts and effectively diminishing DNA oxidation. The results of a DNA fragmentation assay further support the capacity of SAM to ameliorate DEN-induced hepatic malignancy. These results revealed the role of ecCEBPA and UCA1 in HCC and suggest that these lncRNAs may be helpful as prognostic and analytical biomarkers of HCC. Curiously, SAM readily targets the studied genes via inhibiting PI3K/Akt signaling pathway, which should make SAM an appealing agent for both chemoprevention and treatment of HCC.

Retraction: Role and potential targeting of hepatic apurinic/apyrimidinic endonuclease-1 and cyclin-dependent kinase-4 in hepatocellular carcinoma

Apurinic/apyrimidinic endonuclease/redox element 1 (APE1/Ref-1) is a pervasive multifunctional protein required in the DNA base extraction repair (BER) pathway and a noteworthy reducing-oxidizing (redox) factor that upgrades the authoritative of various transcription components to DNA. Cyclin-dependent kinases (CDKs) assume a key part in directing the movement of the cell-cycle. The present study evaluates the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in rats. The results indicated that LCB alone and in combination with FnC60 significantly decreased the percent of DNA fragmentation, oxidative DNA damage byproduct (8-OH-2dG) and the mRNA expression of APE1/Ref-1, CDK-4, retinoblastoma (Rb), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL), and β-arrestin-2 along with decreased protein expression of APE1/Ref-1 and CDK-4; whereas these treatments significantly increased the expression of prot...