Lauric acid attenuates hepato-metabolic complications and molecular alterations in high-fat diet-induced nonalcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin. Moreover, lauric acid significantly elevated the levels of SOD, GSH, catalase, and IL-10. Additionally, it lowered the hepatic levels of MDA, ROS, MPO, 4-HNE, interleukin (IL)-1ß, and tumor necrosis factor (TNF-α). Furthermore, lauric acid significantly up-regulated the hepatic expression of IRS1, AMPK, PI3K, and SIRT1 genes. In parallel, lauric acid could improve the histopathological picture of the liver and reduce the liver apoptosis via decreasing the expression of annexin V (Anx V). Finally, our data proposed that lauric acid could be an effective candidate for the NAFLD treatment.

Evaluation of Fasting and Probiotics in Reducing Postweaning Stress in Rabbits: Study of their Effects on Biochemical and Gene expression Patterns.

Postweaning stress in mammalian in vivo models leads to significant oxidative stress in the body as well as inducing hormonal disturbance. In this study, we assessed progressive alterations in reactive oxygen species (ROS), which at high levels can show oxidative stress, in addition to oxidative damage to the DNA structure of rabbits. Different groups of rabbits were fasted for 48 h per week for 3 weeks, fed a commercial diet with probiotics added (200 mg of Bacillus licheniformis and Bacillus subtilis), and fasted while being treated with probiotics. The results showed that weaning induced a significant elevation in oxidative stress markers, such as the ROS-related genes malate dehydrogenase 1 (MDH1) and flavin-containing monooxygenase 2 (FMO2), DNA damage, and hormonal disturbance. However, probiotic treatment resulted in significant decreases in the levels of malondialdehyde, cortisol, and triiodothyronine (T3); DNA damage; and apoptosis, as well as changes in the expression of ROS-related genes. On the other hand, supplementation with probiotics reduced these postweaning stress signs in fasted animal models by elevating the genes encoding catalase and superoxide dismutase as well as increasing glutathione peroxidase (GSH-Px), glutathione-s-transferase, alkaline phosphatase, glucose, and thyroxin (T4) levels. The results suggest that supplementation with probiotics accompanied by a fasting program could decrease oxidative stress, ROS genes, and genomic DNA damage and improve the hormonal status that is induced by postweaning stress in mammalian in vivo models.

Inflammatory mediators, oxidative stress and genetic disturbance in rheumatoid arthritis rats supported by alfalfa seeds metabolomic constituents via blocking interleukin-1receptor.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of Medicago sativa L. (MS) (alfalfa) seeds and explore its therapeutic impact against RA in rats. Arthritis was induced by complete Freund's adjuvant (CFA) and its severity was assessed by the arthritis index. Treatment with MS seeds butanol fraction and interlukin-1 receptor antagonist (IL-1RA) were evaluated through measuring interlukin-1 receptor (IL-1R) type 1 gene expression, interlukin-1 beta (IL-1ß), oxidative stress markers, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), caspase-3 (Cas-3), intracellular adhesion molecule-1 (ICAM-1), DNA fragmentation, and chromosomal damage. Total phenolics/ flavonoids content in the ethyl acetate, butanol fraction and crude extract of MS seeds were estimated. The major identified compounds were Quercetin, Trans-taxifolin, Gallic acid, 7,4'-Dihydroxyflavone, Cinnamic acid, Kudzusaponin SA4, Isorhamnetin 3-O-beta-D-2'',3'',4''-triacetylglucopyranoside, Apigenin, 5,7,4'-Trihydroxy-3'-methoxyflavone, Desmethylxanthohumol, Pantothenic acid, Soyasapogenol E, Malvidin, Helilandin B, Stigmasterol, and Wairol. Treatment with MS seeds butanol fraction and IL-1RA enhanced all the biochemical parameters and the histopathological features of the ankle joint. In conclusion, Trans-taxifolin was isolated for the first time from the genus Medicago. MS butanol fraction seeds extract and IL-1 RA were considered as anti-rheumatic agents.

Assessing the Efficacy of Fenugreek Saponin Nanoparticles in Attenuating Nicotine-Induced Hepatotoxicity in Male Rats.

During smoking, nicotine, the most bountiful compound in cigarettes, is absorbed into the body by the lungs and quickly metabolized in the liver, causing three major adverse impacts such as toxic, neoplastic, and immunomodulatory effects. Saponins extracted from several plants are reported to exhibit various biological actions, such as anticancer effects. So, the potential protective effect of fenugreek saponin and nanofenugreek saponin against toxicity induced by nicotine in male rats was investigated in this study. Animals were exposed to nicotine (1.5 mg/kg/day) and/or treated with fenugreek saponin (25, 50, and 100 mg/kg/day) and nanofenugreek saponin (20, 40, and 80 mg/kg/day). Comet assays, histopathological examination, and analyses for the expression levels of glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) genes in liver tissues as well as the activity of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were conducted. The results revealed that nicotine treatment induced a significant increase in DNA damage, decrease in the expression levels of (GLAST) and (GLT-1) genes, and increase in histopathological alterations in liver tissues. Moreover, nicotine treatment induced a significant reduction in the activity of antioxidant enzymes GPx and GST. On the other hand, administration of fenugreek saponin or nanofenugreek saponin with nicotine significantly decreased the DNA damage, increased the expression levels of (GLAST) and (GLT-1) genes, and decreased histopathological alterations in liver tissues. Additionally, a significant increase in the activities of GPx and GST was observed. The results suggested that DNA damage and histological injuries induced by nicotine were decreased by the administration of fenugreek saponin or nanofenugreek saponin; thus, fenugreek saponin and nanofenugreek saponin can be used as ameliorative agents against nicotine toxicity.

Evaluation of Mitigation Role of L-Phenylalanine-Based Low-Molecular-Weight Gelator against Oil Pollution-Induced Nile Tilapia Toxicity.

A lot of oil is leaked into aquatic environments, significantly impacting fish health and, consequently, human populations. This study aimed to introduce an L-phenylalanine-based low-molecular-weight gelator (expressed as Z-Phe-C18) as a smart remediation tool for oil spills. Several groups of Nile tilapia were allocated in aquaria exposed to different doses of crude engine oil with/without the organogelator for 4 weeks. The results revealed a significant increase in biochemical oxygen demand, chemical oxygen demand, electrical conductivity, and total dissolved solids in water samples of fish aquaria exposed to oil pollution. The antioxidant activity levels, micronucleus formation, and expression patterns of stress-related genes were significantly higher in the livers of fish exposed to crude oil than in those of control fish. On the contrary, fish groups exposed to oil pollution and treated with the organogelator indicated that antioxidant enzymes, micronucleus incidence, and gene expression alteration of stress-related genes declined compared with those exposed to oil pollution only. The results suggest that oil pollution can induce oxidative stress via the enhancement of oxygen free radical formation. On the contrary, oil removal by the organogelator decreases oxidative stress and consequently strengthens fish immunity. So, we can conclude that organogelator treatment is promoting oxidative resistance development by increasing the activities of antioxidant enzymes, which are important in protection against oil pollution and preventing peroxidation of fish tissues. Promisingly, the organogelator could be used as a tool for the remediation of oil pollution in aquatic environments.

Discovery of novel benzofuran-based derivatives as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis, biological evaluation, molecular docking and 3D-QSAR investigation.

A series of novel benzofuran-based compounds 7a-s were designed, synthesized, and investigated in vitro as acetylcholinesterase inhibitors (AChEIs). Compounds 7c and 7e displayed promising inhibitory activity with IC50 values of 0.058 and 0.086 µM in comparison to donepezil with an IC50 value of 0.049 µM. The new molecules' antioxidant evaluation revealed that 7c, 7e, 7j, 7n, and 7q produced the strongest DPPH scavenging activity when compared to vitamin C. As it was the most promising AChEI, compound 7c was selected for further biological evaluation. Acute and chronic toxicity studies exhibited that 7c showed no signs of toxicity or adverse events, no significant differences in the blood profile, and an insignificant difference in hepatic enzymes, glucose, urea, creatinine, and albumin levels in the experimental rat group. Furthermore, 7c did not produce histopathological damage to normal liver, kidney, heart, and brain tissues, ameliorated tissue malonaldehyde (MDA) and glutathione (GSH) levels and reduced the expression levels of the APP and Tau genes in AD rats. Molecular docking results of compounds 7c and 7e showed good binding modes in the active site of the acetylcholinesterase enzyme, which are similar to the native ligand donepezil. 3D-QSAR analysis revealed the importance of the alkyl group in positions 2 and 3 of the phenyl moiety for the activity. Overall, these findings suggested that compound 7c could be deemed a promising candidate for the management of Alzheimer's disease.

Anti-Alzheimer activity of new coumarin-based derivatives targeting acetylcholinesterase inhibition.

New 2-oxo-chromene-7-oxymethylene acetohydrazide derivatives 4a-d were designed and synthesized with a variety of bioactive chemical fragments. The newly synthesized compounds were evaluated as acetylcholinesterase (AChE) inhibitors and antioxidant agents in comparison to donepezil and ascorbic acid, respectively. Compound 4c exhibited a promising inhibitory impact with an IC50 value of 0.802 µM and DPPH scavenging activity of 57.14 ± 2.77%. Furthermore, biochemical and haematological studies revealed that compound 4c had no effect on the blood profile, hepatic enzyme levels (AST, ALT, and ALP), or total urea in 4c-treated rats compared to the controls. Moreover, the histopathological studies of 4c-treated rats revealed the normal architecture of the hepatic lobules and renal parenchyma, as well as no histopathological damage in the examined hepatic, kidney, heart, and brain tissues. In addition, an in vivo study investigated the amelioration in the cognitive function of AD-rats treated with 4c through the T-maze and beam balance behavioural tests. Also, 4c detectably ameliorated MDA and GSH, reaching 90.64 and 27.17%, respectively, in comparison to the standard drug (90.64% and 35.03% for MDA and GSH, respectively). The molecular docking study exhibited a good fitting of compound 4c in the active site of the AChE enzyme and a promising safety profile. Compound 4c exhibited a promising anti-Alzheimer's disease efficiency compared to the standard drug donepezil.

Febuxostat attenuates aluminum chloride-induced hepatorenal injury in rats with the impact of Nrf2, Crat, Car3, and MNK-mediated apoptosis.

Aluminum (Al) is a ubiquitous xenobiotic with known toxicity for both humans and animals. Our study was conducted to investigate the protective role of febuxostat (Feb) against aluminum chloride (AlCl3)-induced hepatorenal injury in rats. Hepatorenal injury was induced by oral administration of AlCl3 (40 mg/kg b.w.), for 2 months. Twenty-four male Sprague-Dawley rats were randomly allocated into four groups (six rats/group). The first group received the vehicle thought the experiment. The second group was considered as a control positive group. The third and fourth groups received oral treatment of Feb (10 mg/kg.b.w.) and (15 mg/kg.b.w.), respectively with AlCl3, concurrently for 2 months. Twenty-four hours, after the last treatment, serum biochemical, molecular, histopathology, and immunohistochemical studies were evaluated. Our findings showed that rats intoxicated with Alcl3 had disturbed biochemical picture. In addition, intoxication with AlCl3 increased oxidative stress and apoptosis, as demonstrated by an increase in malodialdeyde (MDA), carnitine o-acetyltransferase (Crat), and carbonic anhydrase (Car3) with a decrease in glutathione (GSH), MAP kinase-interacting serine/threonine kinase (MNK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) mRNA expression. Furthermore, the levels of tumor necrosis factor-alpha (TNF-α) and the levels of caspase-3 were elevated with sever hepatic and renal pathological changes. Conversely, Feb (15 mg/kg.b.w.) could improve the serum biochemical indices and repressed MDA, Crat, and Car3 levels, whereas it increased GSH, MNK, and Nrf2 levels. Feb inhibited the apoptotic effect of AlCl3 in the liver and kidney by decreasing caspase-3 and TNF-α expression. The protective effect of Feb against AlCl3 toxicity was confirmed by histopathological findings. Moreover, molecular docking studies supported the anti-inflammatory effect of Feb due to its significant binding interactions with cyclooxygenase-1 (COX-1), NF-kappa-B-inducing kinase (NIK), and mitogen-activated protein kinases-p38 (MAPK-p38). The findings suggest that Feb system Feb can avert Alcl3-induced hepatotoxicity and nephrotoxicity by enhancing the antioxidant defense system, and inhibiting the inflammatory cascade and apoptosis.

Estimation of Early Postmortem Interval from Long Noncoding RNA Gene Expression in the Incised Cutaneous Wound: An Experimental Study.

The assessment of alteration of postmortem RNA expression has forensic significance in estimating postmortem interval. To evaluate wound healing progression and the effect of different postmortem intervals, histopathological changes, immunohistochemical matrix metalloproteinase-9 (MMP-9) expression, and long noncoding fatty acid oxidation (lncFAO), RNA expression was assessed in the incised cutaneous wound model. A full-thickness cutaneous wound was inflicted on 75 rats. All 15 rats were sacrificed at different post-infliction intervals (0, 2, 4, 8 and 10 days), and the cutaneous wounds (n = 5) were excised at different postmortem intervals (0, 5, and 24 h after euthanasia). The maximal inflammatory healing stage was detected at day 4 post-infliction, while near complete healing, thick mature collagen deposition was detected at day 10 post-infliction. LncFAO expression was significantly over-expressed with increasing wound age. MMP-9 was detectable on injury day with continuous elevation until 8 days post-wounding, which later decreased. Although histopathological and immunohistochemical examinations within 24 h postmortem did not show any remarkable changes, lncFAO RNA expression showed a significant negative correlation with hours passed since death. The combined use of histopathological changes, immunohistochemical expression of MMP-9, and molecular expression of lncFAO could be appropriate in wound dating verification. Among these factors, lncFAO could be a reliable indicator in postmortem interval estimation.

Chromosomal aberrations, DNA damage, and biochemical disturbances induced by silver nanoparticles in mice: role of particle size and natural compounds treatment.

CONTEXT: Nanotechnology is widely used nowadays in several fields of industry, engineering, and medicine, the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS). OBJECTIVE: The potential toxicity AgNPs of damages to hepatic cells, hesperidin, and naringin role for their protective effect against the increase of ROS due to AgNPs toxicity. They can be restored, most cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological analysis. MATERIALS AND METHODS: Toxicity was induced by an oral dose of Ag NPs of (20-100 nm) for one month, after that treated with hesperidin, naringin (100 mg/kg) for three weeks, malondialdehyde (MDA) levels, nitric oxide (NO), glutathione (GSH) and catalase were estimated. Also, aminotransferases (AST and ALT), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), albumin, and total bilirubin were determined, following Chromosomal aberrations, DNA breaks, and histological analyses. RESULTS: hesperidin, and naringin treatment, recorded amelioration in most biochemical, genetic, and spermatogenesis disturbances Also, histological Investigations were improved. CONCLUSION: Their biological safety problems, such as potential toxicity on cells, tissue, and organs should be paid enough attention, hesperidin and naringin amelioration fundamental alterations, as hepatic architectural and DNA damage, related to its role as an antioxidant and anti-inflammatory agent.

Alleviation of nicotine-induced reproductive disorder, clastogenicity, and histopathological alterations by fenugreek saponin bulk and nanoparticles in male rats.

Nicotine is the most abundant ingredient in cigarette smoking and has serious side effects on the lung, heart, reproductive system, and many other human organs. Saponins extracted from many plants exhibit multiple biological actions such as anti-cancer effects. Therefore, the possible protective effect of fenugreek saponin (FS) and nanofenugreek saponin (NFS) against nicotine-induced toxicity in male rats was investigated in this study. Animals were divided into a control group and the nicotine (1.5 mg/kg/day), FS (25, 50, and 100 mg/kg/day), or/and NFS (20, 40, and 80 mg/kg/day) administered groups. Micronucleus assay, histopathological, and sperm abnormality examinations as well as measurement of the acetylcholinesterase (AChE) gene expression were conducted. Our findings revealed that nicotine treatment induced significant increases in the incidence of micronucleus, sperm abnormalities, and expression levels of AChE in addition to inducing histopathological changes in rat testis. On the other hand, administration of FS or NFS with nicotine significantly decreased the incidence of micronuclei and the percentage of sperm abnormalities as well as the expression levels of AChE gene. Moreover, nicotine-induced histological alterations were reduced by given FS or NFS with nicotine. In conclusion, nicotine-induced sperm abnormalities, chromosomal damage, and histological injuries were mitigated by administration of FS or NFS with nicotine, and thus, FS and NFS could be used as ameliorating agents against nicotine toxicity.

Neuroprotective effects of onion and garlic root extracts against Alzheimer's disease in rats: antimicrobial, histopathological, and molecular studies.

Alzheimer's disease (AD) is a brain disorder and the main reason for dementia. In this regard, there is a need to understand the alterations that occur during aging to develop treatment strategies to mitigate or prevent neurodegenerative consequences. Onion and garlic root extracts contain natural polyphenols with high antioxidant capacity; therefore, the present study aimed to investigate the protective effect of these extracts free from mycotoxin contamination on a rat model of AD. Antifungal and antibacterial assays were performed for onion and garlic extracts. Several groups of AD-induced rats were administered 1, 2, and 3 mg/kg onion or garlic extract through intragastric intubation for 30 days. After treatment, histopathological analysis, expression of apoptosis-related genes, and analyses of DNA damage and reactive oxygen species (ROS) generation were conducted in the brain tissues. The results indicate that treatment of AD-induced rats with several doses of onion and garlic root extracts decreased histopathological lesions, the expression levels of apoptotic genes, and the rate of DNA damage and inhibited intracellular ROS generation in the brain tissues. The results suggest that the protective role of onion root extract could be attributed to its content of flavonoids and flavonoid compounds through the improvement of antioxidant capacity and regulation of gene expression patterns. The higher activity levels of free radical scavenging of azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and antioxidant ferric reducing antioxidant power (FRAP) levels found in garlic root extract are most probably responsible for its protective effect against neurodegenerative damage.

Bioactive compounds and therapeutic role of Brassica oleracea L. seeds in rheumatoid arthritis rats via regulating inflammatory signalling pathways and antagonizing interleukin-1 receptor action.

CONTEXT: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and systematic polyarthritis. OBJECTIVE: The present study aimed to isolate and identify the phenolic constituents in Brassica oleracea L. (Brassicaceae) seeds methanolic extract and evaluates its effect against rheumatoid arthritis in rats referring to the new therapy; interleukin-1 receptor antagonist (IL-1RA). MATERIALS AND METHODS: The GC/MS profiling of the plant was determined. Arthritis induction was done using complete Freund's adjuvant. Arthritis severity was assessed by percentage of edema and arthritis index. IL-1 receptor type I gene expression, interleukin-1ß (IL-1ß), oxidative stress markers, protein content, inflammatory mediators, prostaglandin-E2 (PGE2), genetic abnormalities and the histopathological features of ankle joint were evaluated. RESULTS: For the first time twelve phenolic compounds had been isolated from the seeds extract. Treatment with extract and IL-1RA improved the tested parameters by variable degrees. CONCLUSIONS: RA is an irreversible disease, where its severity increases with the time of induction. Brassica oleracea L. seeds extract is considered as a promising anti-arthritis agent. IL-1 RA may be considered as an unusual therapeutic agent for RA disease. More studies are needed to consider the seeds extract as a nutraceutical agent and to recommend IL-1RA as a new RA drug.

DNA Damage and Expression Profile of Genes Associated with Nephrotoxicity Induced by Butralin and Ameliorating Effect of Arabic Gum in Female Rats.

Nephrotoxicity induced by exposure to environmental pollution, including herbicides, is becoming a global problem. Natural products are the prime alternative scientific research as they express better medicinal activity and minor side effects compared with a variety of synthetic drugs. This study was performed to evaluate the nephroprotective proficiency of Arabic gum against butralin-induced nephrotoxicity. Adult female rats were supplemented with Arabic gum (4.3 g/kg b.wt) and/or butralin (312 mg/L) in drinking water for 30 days. The results found that markers of serum kidney function, oxidative stress biomarkers, DNA damage, and expression of kidney specific genes (Acsm2, Ace, and Ace2) as well as histopathological examination in treated rats were conducted. Butralin-treated rats showed a rise in serum creatinine (41%), BUN (47.3%), and MDA (140.9%) as well as decrease in activity of the antioxidant markers (CAT (-21%); GPx (-70.7%); and TAC (43.2%)) in comparison with the control group. In addition, butralin treatment increased the DNA damage (221%); altered the expression levels of Acsm2, Ace, and Ace2 (-51.6%, 141.6%, and 143% respectively); and elevated histopathological lesions in the kidney tissues. Pretreatment of Arabic gum prevented butralin-prompted degenerative changes of kidney tissues. The results suggested that the protective effect provided by Arabic gum on renal tissues exposed to the herbicide butralin could be attributed to enhancement of antioxidants and increase the free radical scavenging activity in vivo.

Flavonoids from Barnebydendron riedelii leaf extract mitigate thioacetamide-induced hepatic encephalopathy in rats: The interplay of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.

Phytochemical investigation of the butanol fraction (BUF) derived from the 70% aqueous methanolic leaf extract of Barnebydendron riedelii led to the isolation of three flavonoid glycosides; kaempferol-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside, quercetin-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-galactopyranoside and quercetin-3-O-α-l-rhamnopyranosyl-(1 â†’ 6)-ß-d-glucopyranoside. Docking studies were fulfilled to validate the possible bio-properties of BUF toward nuclear factorkappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). The protective role of BUF against behavioral, biochemical, molecular, histopathological and immunohistochemical alterations in thioacetamide (TAA)-induced hepatic encephalopathy in rats was investigated. The toxicological studies indicated that BUF was safe up to 2000 mg/kg bw. Prior to TAA intoxication, rats were orally treated with either BUF at multiple doses (70, 140 and 280 mg/kg bw) or lactulose (8 mL/kg bw) for 14 consecutive days. On the 13th and the 14th day, TAA (200 mg/kg bw/day) was intraperitoneally injected. The BUF significantly improved motor impairment, ameliorated cognitive deficits and attenuated TAA-induced hepatotoxicity. Moreover, BUF controlled the inflammatory processes by suppressing the hepatic inflammatory cytokine; interleukin-6 (IL-6) as well as its pro-inflammatory mediator; NF-κB supporting the molecular docking assessment. The brain neurotransmitters; dopamine, serotonin and noradrenaline, as well as ammonia levels were improved in BUF-treated TAA-intoxicated animals in a dose-dependent manner. Furthermore, BUF administration to TAA-intoxicated rats modulated the Nrf2 and heme oxygenase 1 (HO-1) genes expression in liver and brain tissues. The histological evaluation showed that pretreatment of TAA-intoxicated rats with BUF ameliorated the degenerative effects of TAA on liver and brain tissues as well as reduced the activation of cellular apoptotic marker; caspase-3 and glial fibrillary acidic protein (GFAP+) astrocytes. In conclusion, the observed hepato-neuroprotective effect of BUF is attributed to its flavonoidal content through its modulatory effects on of NF-κB/IL-6 and Nrf2/HO-1 signaling pathways.

DNA damage and genetic aberration induced via different sized silver nanoparticles: Therapeutic approaches of Casimiroa edulis and Glycosmis pentaphylla leaves extracts.

Potential of Casimiroa edulis and Glycosmis pentaphylla leaves extracts were investigated against the effect of two different particle sizes of silver nanoparticles induced toxicity in mice. Mice received silver nanoparticles (AgNPs) (100 mg/kg) with 20 and 100 nm for four weeks followed by daily oral dose of extracts (500 mg/kg) for three weeks. C. edulis leaves identified fourteen phenolic compounds while, G. pentaphylla leaves identified, twelve phenolic compounds. Additionally, biochemical, genotoxicity, mutagenicity, and histopathological investigations were carried out, revealed that liver function activities, lipid profile, hydrogen peroxide, and C-reactive protein were significantly elevate post AgNPs exposure. While, superoxide dismutase, glutathione-S-transferases, and glutathione peroxidase significantly reduce. A marked amelioration in all detected biomarkers, improved histopathological changes and repair DNA damage after treated with C. edulis and G. pentaphylla leaves extracts. These extracts are used for the first time as promising candidate therapeutic agents against toxicity induced by AgNPs. PRACTICAL APPLICATIONS: The potential applications of AgNPs make it necessary to investigate the possible toxicity associated with release of free silver ions in the biological system. AgNPs of varying particle sizes had toxic effects as evidenced by alterations in some cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological indices on mice. Casimiroa edulis and Glycosmis pentaphylla leaves extracts are used for the first time as promising candidate therapeutic, where they are able to ameliorate the toxicity induced via AgNPs and record vacillate percentage of improvement in the selected biomarkers, as a result of the bioactive secondary metabolites especially flavonoids and other polyphenolic compounds.

Molecular characterization and immunohistochemical localization of tilapia piscidin 3 in response to Aeromonas hydrophila infection in Nile tilapia.

The antimicrobial activity of tilapia piscidin 3 (TP3) was determined in vitro against a locally isolated Aeromonas hydrophila. A 388 bp fragment was amplified from the TP3 cDNA and sequenced. The coding sequence (CDS) of TP3 was estimated to be 231 bp codes for 76 amino acids long and stop codon. In silico analysis was performed to detect both the signal peptide and the prodomain cleavage sites to follow the amino acids number 22 and 70, respectively. Based on this, a peptide 23 amino acids long with a remarkably high computed antimicrobial probability was synthesized and used in the subsequent experiments. The antimicrobial activity of TP3 was determined with minimum inhibitory concentration (MIC) and minim um bactericidal concentration (MBC) methods. TP3 exhibited relatively weak antimicrobial activities against the tested bacteria. A challenge experiment was then performed in Nile tilapia with low and high doses of A. hydrophila, followed by timely recognition; after 3, 6, 24 h, and 7 days of the specific TP3 gene expression, immunohistochemical localization was also performed. Histopathological examination revealed provoked inflammatory responses and congestion in the same organs of TP3 expression. Immunohistochemical localization showed that A. hydrophila induced tilapia fish to express TP3 after 24 h within the gills, intestine, hepatopancreas, spleen, and posterior kidney. In quantitative real time (RT)-polymerase chain reaction analysis, the high dose showed higher mRNA expression levels than the low dose, and its expression levels increased in the A. hydrophila-infected fish. It was therefore concluded that TP3 plays an essential role in fish immunity.

Piscidin 4: Genetic expression and comparative immunolocalization in Nile tilapia (Oreochromis niloticus) following challenge using different local bacterial strains.

The antimicrobial activity of tilapia piscidin 4 (TP4) was determined in vitro against four bacterial strains, Aeromonas hydrophilla, Pseudomonas fluorescens, Streptococcus iniae and Vibrio anguillarum. Nile tilapia were infected with low and high doses of the tested pathogens; after 3, 6, 24 h and 7 days of the specific TP4 gene expression, tissue immunolocalization was also performed. Histopathological examination revealed septicaemia and necrosis of hemopoietic tissue for all of the tested bacteria. Immunolocalization showed abundance in S. iniae-infected fish tissues. Quantitative RT-PCR analysis revealed that high doses raised mRNA expression levels compared to low doses and expression levels increased in the infected fish, particularly after 24 h, indicating that TP4 exerts potent bactericidal activity against some fish pathogens and plays an essential role in fish immunity.

Over-gene expression in the apoptotic, oxidative damage and liver injure in female rats exposed to butralin.

The present study is the first report for studying the toxic effects of butralin herbicide on COX2, BAX, and Bcl2 gene expression, oxidative stress, and liver damage in female rats. Female rats were received butralin in drinking water for 28 days at concentration 4.16, 312, and 3120 mg/L that corresponded to the acceptable daily intake (ADI), no observed adverse effect level (NOAEL), and 10 NOAEL, respectively. Butralin decreased body weights and increased relative liver weight of female rats exposed to high dose. It caused significant elevation in liver function enzymes, lipid peroxidation, and reactive oxygen species (ROS). Antioxidant enzymes were decreased in liver tissue by increasing the dose. Butralin induced over-expression in the apoptotic related genes including COX2, BAX, and Bcl2 and pathological alteration in the liver of female rats especially at a high dose. It can be concluded that butralin induced oxidative damage and liver injure. The mechanism of damage could be due to generate reactive oxygen species, and increase lipid peroxidation that causes over-expression in the apoptotic related genes including COX2, BAX, and Bcl2. From the Benchmark dose (BMD) approach, there is dose-dependent manner in body weight, AST, ALT, and ALP, and ALT is a very sensitive parameter.

Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson's disease mice model.

Parkinson's disease (PD) is the second common age-related neurodegenerative disease. It is characterized by control loss of voluntary movements control, resting tremor, postural instability, bradykinesia, and rigidity. The aim of the present work is to evaluate curcumin, niacin, dopaminergic and non-dopaminergic drugs in mice model of Parkinson's disease through behavioral, biochemical, genetic and histopathological observations. Mice treated with rotenone rerecorded significant increase in adenosine A2A receptor (A2AR) gene expression, α synuclein, acetylcholinesterase (AchE), malondialdehyde (MDA), angiotensin-II (Ang-II), c-reactive protein (CRP), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels as compared with the control group. While, significant decrease in dopamine (DA), norepinephrine (NE), serotonin (5-HT), superoxide dismutase (SOD), reduced glutathione (GSH), ATP, succinate and lactate dehydrogenases (SDH &LDH) levels were detected. Treatment with curcumin, niacin, adenosine A2AR antagonist; ZM241385 and their combination enhanced the animals' behavior and restored all the selected parameters with variable degrees of improvement. The brain histopathological features of hippocampal and substantia nigra regions confirmed our results. In conclusion, the combination of curcumin, niacin and ZM241385 recorded the most potent treatment effect in Parkinsonism mice followed by ZM241385, as a single treatment. ZM241385 succeeded to antagonize adenosine A2A receptor by diminishing its gene expression and ameliorating all biochemical parameters under investigation. The newly investigated agent; ZM241385 has almost the same pattern of improvement as the classical drug; Sinemet®. This could shed the light to the need of detailed studies on ZM241385 for its possible role as a promising treatment against PD. Additionally, food supplements such as curcumin and niacin were effective in Parkinson's disease eradication.