Leverage of Salvadora persica and Pulicaria undulata extracts in Escherichia coli-challenged broiler chickens.

Escherichia coli (E. coli) is a significant challenge in the poultry industry due to their related use of antimicrobial compounds and the drastic losses in production and livability. This study investigated the preventive impacts of dietary supplementation of Salvadora persica (SP) and/or Pulicaria undulata (PU) extracts on growth traits, biochemical and immune parameters, and related gene expression of E. coli-infected broilers. A total of 120 one-day-old Cobb broilers were used. The chicks were allocated into eight equal groups (3 replicates/ group; 5 chicks per each replicate) as follows: G1; control negative, G2; SP-treated, G3; PU-treated, G4; SP/PU-treated, G5; E. coli infected, G6; E. coli infected and SP-treated, G7; E. coli infected and PU-treated, G8; E. coli infected and SP/PU-treated groups. Results revealed significant improvement in average body weight (ABW), average weight gain (AWG) and feed conversion ratio (FCR) in broilers fed diets supplemented with SP and/or PU compared to control and E. coli infected groups. Moreover, significant (P < 0.05) reduction in ALT, AST, creatinine, and uric acid was reported in other treated groups compared to the single E. coli-infected broilers. On the contrary, a significant increase (P < 0.05) in serum immunoglobulin and protein concentration was also reported in treated groups when compared to E. coli-infected untreated group. In addition, feeding broilers with SP and/or PU significantly improved (P < 0.05) the relative weight of immune-related organs and gene expression of TLR-15, with subsequent down-regulation of IL-1ß and TNF-α mRNA transcripts. Supplementing broilers with dietary SP and/or PU could be promising in the prevention of E. coli infection via stimulating significant improvement of immune-related gene expression, immune-related organ weight, and down-regulation of inflammatory-related genes, with subsequent enhancement of the growth performance of broiler chickens.

Lutein Modulates Oxidative Stress, Inflammatory and Apoptotic Biomarkers Related to Di-(2-Ethylhexyl) Phthalate (DEHP) Hepato-Nephrotoxicity in Male Rats: Role of Nuclear Factor Kappa B.

Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues' redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity.

Effects of ginger extract and/or propolis extract on immune system parameters of vaccinated broilers.

Newcastle disease (ND), avian influenza (AI, H5N8), and infectious bronchitis (IB) are important diseases in the poultry industry and cause significant losses. Vaccination is the most practical method for controlling infectious diseases. To reduce vaccination costs and several disorders in poultry farms, using herbal water supplements for immunomodulation with vaccination is critical to improving or preventing some conditions in the poultry industry. However, drinking water supplementation of ginger extract (GE)/propolis extract (PE) alone/in combination may increase broilers' humoral and cellular immunity due to the immunomodulatory effects of ginger and propolis. This protocol aimed to see how GE/PE alone or in combination improved the immunity, immune organ gene expression, and histology of the immune organs of broilers for 35 d after vaccination against NDV, H5N8, IBV, and IBDV. The chicks were dispensed into 5 groups according to GE and/or PE with vaccination. The control group was offered normal drinking water without any supplements or vaccinations. The GE group was supplemented with ginger extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The GE+PE group was supplemented with GE (0.5 mL/L drinking water) and PE (0.5 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The PE group was supplemented with propolis extract (1 mL/L drinking water) in the drinking water before and after vaccination for 2 and 3 d, respectively. The fifth group was the vaccinated untreated group. This experiment showed the immunomodulatory properties of GE and/or PE against 3 common diseases, NDV, AI, and IB, in broiler chicken farms for 35 d applied to a vaccination program. Thus, ginger extract and propolis extract supplementation in drinking water increased antibody titer, INF, IL10, and IL2 and TLR3 gene expression in the bursa of Fabricius, thymus, and spleen, respectively, as well as cellular immunity as indicated by increased CD3, CD4, and CD8 in the bursa of Fabricius, thymus, and spleen, respectively, with normal lymphocytes in the medulla of the bursa, thymus, and spleen. In conclusion, propolis extracts alone or with GE improved all of the metrics mentioned above without harming the histology of the immune organs.

Ameliorative effect of nanocurcumin and Saccharomyces cell wall alone and in combination against aflatoxicosis in broilers.

BACKGROUND: The adverse effect of aflatoxin in broilers is well known. However, dietary supplementation of Saccharomyces cell wall and/or Nanocurcumin may decrease the negative effect of aflatoxin B1 because of the bio-adsorbing feature of the functional ingredients in Yeast Cell Wall and the detoxification effect of curcumin nanoparticles. The goal of this study was to see how Saccharomyces cell wall/Nanocurcumin alone or in combination with the aflatoxin-contaminated diet ameliorated the toxic effects of aflatoxin B1 on broiler development, blood and serum parameters, carcass traits, histology, immune histochemistry, liver gene expression, and aflatoxin residue in the liver and muscle tissue of broilers for 35 days. Moreover, the withdrawal time of aflatoxin was measured after feeding the aflatoxicated group an aflatoxin-free diet. Broiler chicks one day old were distributed into five groups according to Saccharomyces cell wall and/or nanocurcumin with aflatoxin supplementation. The G1 group was given a formulated diet without any supplements. The G2 group was supplemented with aflatoxin (0.25 mg/kg diet) in the formulated diet. The G3 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in the formulated diet. The G4 group was supplemented with aflatoxin (0.25 mg/kg diet) and nanocurcumin (400 mg/kg) in the formulated diet. The G5 group was supplemented with aflatoxin (0.25 mg/kg diet) and Saccharomyces cell wall (1 kg/ton diet) in combination with nanocurcumin (200 mg/kg) in the formulated diet. RESULTS: According to the results of this study, aflatoxin supplementation had a detrimental impact on the growth performance, blood and serum parameters, carcass traits, and aflatoxin residue in the liver and muscle tissue of broilers. In addition, aflatoxin supplementation led to a liver injury that was indicated by serum biochemistry and pathological lesions in the liver tissue. Moreover, the shortening of villi length in aflatoxicated birds resulted in a decrease in both the crypt depth ratio and the villi length ratio. The expression of CYP1A1 and Nrf2 genes in the liver tissue increased and decreased, respectively, in the aflatoxicated group. In addition, the aflatoxin residue was significantly (P ≤ 0.05) decreased in the liver tissue of the aflatoxicated group after 2 weeks from the end of the experiment. CONCLUSION: Saccharomyces cell wall alone or with nanocurcumin attenuated these negative effects and anomalies and improved all of the above-mentioned metrics.

Biochemical, molecular and cytological impacts of alpha-lipoic acid and Ginkgo biloba in ameliorating testicular dysfunctions induced by silver nanoparticles in rats.

Silver nanoparticles (AgNPs) are commonly utilized in medicine. However, they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testicular tissues due to their nano size, which allows them to pass through blood-testicular barriers. The goal of this study was to see if alpha-lipoic acid (LA) or Ginkgo biloba (GB) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups: control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50 mg/kg b.w, 3 times a week; LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100 mg LA/kg b.w; and GB + AgNPs group injected with AgNPs and orally given GB extract 120 mg/kg b.w for 30 consecutive days. Biochemical changes (testosterone, ACP, and prostatic acid phosphatase), oxidative indices, mRNA expression of proapoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes in testicular tissues were investigated. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs-treated rats. As well, there were lowering in tGSH, GSH GR, GPx, and elevation in MDA and GSSG values. AgNPs-exposed rats expressed downregulation of testicular thirodexin-1 (Txn-1), transforming growth factor-1ß (TGF-1ß), anti-apoptotic (BCL-2), and upregulaion of proapoptotic biomarkers (BAX) mRNA expressions. Strong positive action to BAX and lowering the action of Ki-67 antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with LA or GB could be beneficial in reducing the harmful effects of AgNPs on the testicles.

Nanocurcumin alleviates inflammation and oxidative stress in LPS-induced mastitis via activation of Nrf2 and suppressing TLR4-mediated NF-κB and HMGB1 signaling pathways in rats.

Coliform mastitis is a worldwide serious disease of the mammary gland. Curcumin is a pleiotropic polyphenol obtained from turmeric, but it is hydrophobic and rapidly eliminated from the body. However, nanoformulation of curcumin significantly improves its pharmacological activity by enhancing its hydrophobicity and oral bioavailability. Our study aimed to investigate the possible antioxidant and anti-inflammatory effects of nanocurcumin as a prophylactic against LPS-induced coliform mastitis in rat model, where LPS was extracted from a field strain of Escherichia coli (bovine mastitis isolate). The study was conducted on twenty lactating Wistar female rats divided into four equal groups, and the mastitis model was initiated by injection of LPS through the duct of the mammary gland. The results showed that nanocurcumin significantly attenuated the lipid peroxidation (MDA), oxidized glutathione, the release of pro-inflammatory cytokines (TNF-α and IL-1ß), and the gene expression of TLR4, NF-κB p65, and HMGB1. Meanwhile, it improved the reduced glutathione level and Nrf2 activity and preserved the normal alveolar architecture. These findings suggested that nanocurcumin supplementation can be a promising potential protective approach for coliform mastitis.

Commiphora myrrh Supplementation Protects and Cures Ethanol-Induced Oxidative Alterations of Gastric Ulceration in Rats.

Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were gavaged by ethanol to investigate the protective (before ethanol) and curative (after ethanol) ability of Commiphora myrrh (myrrh) oil and extract against gastric ulcer oxidative alterations induced by ethanol. Myrrh significantly improved ulcer index, histomorphology, and periodic acid Schiff (PAS) impaired by ethanol. In addition, myrrh improved the antioxidant potential of gastric mucosa through enhancement of nuclear factor related to erythroid 2 (Nrf2), total glutathione (GSH), reduced GSH, and oxidized glutathione (GSSG), along with significant reduction in malondialdehyde (MDA) levels. Amelioration of gastric oxidative stress by myrrh enables gastric mucosa to counteract the ethanol's inflammatory and apoptotic processes leading to improved gastric proliferation and healing. Interestingly, myrrh extract showed better protective and curative effects than myrrh oil against gastric ulceration.

The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats.

Acrylamide (ACR) is an unsaturated monomer that served various fields; however, it is a potent neurotoxin. The target of the present study is to explore the neuroprotective efficacy of allicin and melatonin on ACR-induced neurotoxicity. Thirty-six male adult rats were non-selectively separated into six groups: placebo, allicin (20 mg/kg b.w daily per os), melatonin (10 mg/kg b.w 3 times/week per os), ACR (50 mg/kg b.w daily per os), ACR-allicin, and ACR-melatonin at the same doses as the preceding groups. The assessment of brain biomarkers, neurotransmitters, antioxidative status, Nrf2 signaling pathway, and histopathological analyses was performed following 21 days. ACR exposure induced brain lipid and DNA oxidative damage as well as reduced the glutathione (GSH) levels. The obvious brain oxidative injuries contributed to distinct brain dysfunction that was assured by alteration of brain neurotransmitters (serotonin, dopamine, acetylcholine, and acetylcholinesterase) and pathological brain lesions. Furthermore, ACR exposure increased hydroxy deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and amyloid protein (AB1-42). Finally, the mRNA transcripts of brain Keap-1, Nrf2, and NF-kB were upregulated after ACR intoxication. Interestingly, allicin and melatonin alleviated the ACR-induced brain damage assessed by the normalization of the mentioned analyses. The present study demonstrated the protective role of both allicin and melatonin in ACR-prompted neuropathy by alleviation of redox imbalance and enhancement of neurotransmitters as well as relieving DNA damage and anti-inflammatory effect.

Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats.

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

Effects of bovine lactoferrin and chitosan nanoparticles on serum biochemical indices, antioxidative enzymes, transcriptomic responses, and resistance of Nile tilapia against Aeromonas hydrophila.

The present study was carried out to investigate the effects of dietary bovine lactoferrin (BLF) or chitosan nanoparticles (CHN) alone or in combinations on serum biochemical indices, antioxidative capacity, transcriptomic responses, non-specific immunity, and resistance of Nile tilapia (Oreochromis niloticus) against challenge with Aeromonas hydrophila. Fish were fed on the basal diet with no supplements and served as control (CTR), and six other experimental diets containing different levels of BLF (800 and 1200 mg per kg diet), CHN (500 and 1000 mg per kg diet), and their combinations (400 mg BLF plus 250 mg CHN per kg diet, and 600 mg BLF plus 500 mg CHN per kg diet) for 45 days. At the end of the experiment, serum, and tissue specimens (liver and kidney) were collected, fish in all groups were challenged with A. hydrophila and then observed for another ten days to calculate the RPS. Compared to the CTR group, no significant differences were recorded in TP, ALB, GLO, BUN, and CREAT values among all treatments. Serum LYZ, ALT, AST, and ALP enzyme activities were significantly increased in all experimental groups over the CTR (P < 0.05), and their highest values were recorded in the combined treatments. Moreover, dietary supplementation with CHN (1000 mg/kg) and combined treatments significantly increased the SOD, CAT, and GSH-Px enzyme activities compared to other groups (P < 0.05). The highest mRNA expression levels of IGF-1 gene in liver, and IL-1ß, and IFN-γ genes in kidneys were found in CHN (1000 mg/kg) group and combined treatments more than other groups. Interestingly, no, or mild histopathological alterations were noticed in the hepatopancreas and posterior kidney of the treated groups. A significantly higher RPS was identified in the combined treatments challenged with A. hydrophila compared with the CTR group. This study exemplifies the positive impacts of dietary supplementation with BLF or CHN alone or combinations on the antioxidative status, immunity, and disease resistance of Nile tilapia.

Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats.

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1ß, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.

Correction to: Ginkgo biloba mitigates silver nanoparticles-induced hepatotoxicity in Wistar rats via improvement of mitochondrial biogenesis and antioxidant status.

The original publication of this paper contains a mistake. The correct image of figure 3 is shown in this paper.

Ginkgo biloba mitigates silver nanoparticles-induced hepatotoxicity in Wistar rats via improvement of mitochondrial biogenesis and antioxidant status.

Silver nanoparticles (AgNPs) are noble metal nanoparticles, due to their good physicochemical properties, which have been exploited in biological applications. Nanotechnological applications advance very quickly while few literatures assessed the effects of natural products on the risks of nanoparticles in vivo. Thirty male adult rats were enrolled equally into: control, AgNPs (50 mg/kg b.w i.p 3 times/week) and GBE (100 mg/kg b.w daily per os)+AgNPs. After 30 days, the assessment of liver function, antioxidative status, mitochondrial biogenesis, and histopathological analyses were performed. AgNP exposure enhanced the hepatic lipid peroxidation (+ 281.7%) along with a decline in the reduced glutathione (- 58.3%) levels. The apparent hepatic oxidative damage was associated with obvious hepatic dysfunction that was ascertained by alteration of serum liver enzymatic biomarkers, lipid profile, and pathological hepatic lesions. Following AgNP exposure, hepatic silver and calcium contents were increased without changes in the trace element concentrations. Finally, the mRNA transcripts of hepatic PGC-1α, mtTFA, and Nrf2 were downregulated after AgNP exposure. Interestingly, GBE has the ability to alleviate AgNP-induced hepatic damage assessed by augmentation of reduced glutathione level and mitochondrial biogenesis. This study explored the potential protective role of GBE on AgNPs-induced hepatotoxicity via attenuation of oxidative stress, substantial enhancement of cell viability with concomitant mitigating DNA damage, and mitochondrial dysfunction.

Miswak (Salvadora persica) dietary supplementation improves antioxidant status and nonspecific immunity in Nile tilapia (Oreochromis niloticus).

Nile tilapia (Oreochromis niloticus) is the most common aquaculture fish, but is exposed to various pollutants and may be susceptible to infectious diseases due to reduction in their antioxidant status and immune defense. Therefore, researchers have tried to find feed supplements of natural origin to increase the health status of fish and decrease the incidence of drug resistance. The current study was conducted to investigate the effect of dietary supplementation of Miswak (Salvadora persica, SP) on Nile tilapia. Fish were randomly allocated into four experimental groups (30 fish each); the control fish were fed on the basal commercial diet and the SP-treated groups were fed basal diet supplemented with different concentrations 0.5, 1, and 2% for 30 days. The SP supplementations had no significant effects of SP on fish growth performance traits and lipid profiles but augmented the serum protein and globulin levels. The SP significantly improved the hepatic antioxidant status through the significant decrease of malondialdehyde (MDA) and the increases of reduced glutathione (GSH) levels and the activities of total superoxide dismutase (T.SOD), catalase (CAT) and glutathione peroxidase (GPx), especially in the SP 1% group, while glutathione S-transferase (GST) activities were significantly increased due to SP in a dose-dependent manner. The same results were obtained for the mRNA expression of CAT and GPx. Regarding the nonspecific immune status of the fish kidneys, SP, especially SP1, significantly increased interleukin-1 beta (IL-1ß) and interferon-gamma (INF-γ). The data of the present study revealed the protective effect of SP on Nile tilapia health status. Therefore, SP can be considered as a promising feed additive for Nile tilapia.

The possible neuroprotective effects of melatonin in aluminum chloride-induced neurotoxicity via antioxidant pathway and Nrf2 signaling apart from metal chelation.

Aluminum (Al) had well-identified adverse influences on the nervous system mainly through the creation of reactive oxygen species (ROS). Melatonin works as an antioxidant through the inhibition of ROS and attenuating peroxidation of lipids. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a pivotal transcription factor which controls the transcription of antioxidant enzymes. This study was conducted to determine the potential neuroprophylactic impacts of melatonin in aluminum chloride (AlCl3)-initiated neurotoxicity including potential mechanism(s) of action and relevant signaling in rats. Thirty-six male rats were distributed into 4 groups: Control; AlCl3 (50 mg/kg bwt, i.p, 3 times weekly for 3 months); melatonin (5 mg/kg bwt, i.p daily for 2 weeks before AlCl3 and sustained for the next 3 months); and melatonin with AlCl3. Neuronal alterations were histopathologically and biochemically evaluated. The neuronal antioxidant-related genes and relevant Nrf2 protein expression were determined by real-time PCR and Western blotting, respectively. The current data showed a substantial increase in brain damage biomarkers, acetylecholinesterase (AchE) activity, and malondialdehyde (MDA) content while the enzymatic antioxidant expression as glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were substantially attenuated in the aluminum-treated group, with cleared histopathological changes as inflammatory cell infiltration with neuronal degeneration. Supplementation of melatonin resulted in an obvious amelioration in all previous abnormal alteration observed in AlCl3-treated rats rather than increased Al burden and/or altered Fe and Cu homeostasis with upregulating both total and phosphorylated Nrf2 expression. Therefore, the study concluded that melatonin has a potential ability to be neuroprophylactic against Al-induced neurotoxic effect and oxidative damage in the rat brain through upregulating and instigating Nrf2 signaling apart from metal chelation.

Potential role of α-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats.

AIMS: This study explored whether silver nanoparticles (AgNPs) can disrupt tight-junctions integrity resulted in blood-brain barrier dysfunction along with oxidative stress, pro-inflammation, and apoptosis induction. Additionally, neuroprotective activities of α-lipoic acid (LA) and Ginkgo biloba (GB) were investigated. MAIN METHODS: Forty adults rats were enrolled into; Control, AgNPs (50 mg/kg), LA (100 mg/kg) + AgNPs, and GB (120 mg/kg) + AgNPs. After 30 days, neuronal changes were assessed biochemically and histopathologically. Brain tissues oxidative indices, mRNA expression of proinflammatory cytokines and tight-junction proteins and pro-apoptotic biomarker, caspase-3 were investigated. KEY FINDINGS: AgNPs exposure enhanced lipid peroxidation (+195%) along with declines in glutathione (-43%), glutathione peroxidase (-34%), glutathione S-transferase (-31%), catalase (-43%), and superoxide dismutase (-38%) activities in brain tissues. The apparent brain oxidative damage was associated with obvious neuronal dysfunction that was ascertained by neuropathological lesions. AgNPs lowered serum acetylcholine esterase, iron and copper levels, and increased creatine phosphokinase and creatine phosphokinase-brain type activities. Following AgNPs exposure, brain silver and iron contents were increased, but the copper level was decreased. AgNPs up-regulated TNF-α (6.5-fold) and IL-1ß (8.9-fold) transcript levels, and simultaneously over-expressed the caspase-3 protein in cerebrum and cerebellum inducing cell apoptosis. Moreover, AgNPs down-regulated the transcript levels of tight-junction proteins; JP-1 (0.65-fold) and JAM-3(0.81-fold). SIGNIFICANCE: LA and relatively GB improved the serious effects of AgNPs on the blood-brain barrier function and tight-junction proteins through their antioxidants, anti-inflammatory, and anti-apoptotic efficacies. Co-treatment with LA or GB may be favorable in ameliorating the neurotoxic side effects of AgNPs.

The molecular and biochemical insight view of lycopene in ameliorating tramadol-induced liver toxicity in a rat model: implication of oxidative stress, apoptosis, and MAPK signaling pathways.

The influence of tramadol (TD) on hepatic tissue and the potential efficiency of lycopene to mitigate TD-induced hepatotoxic impacts were determined. Forty male albino rats were allocated into four groups: group I, untreated (placebo); group II, injected with TD (15 mg kg-1) intraperitoneally (i.p.); group III, gastrogavaged with lycopene (10 mg kg-1) per os (p.o.); and group IV received TD with lycopene with the same mentioned doses for 15 days. The results demonstrated that TD induced augmentation in tissue lipid peroxidation biomarker and disturbance in the antioxidant homeostasis and elevated the activity of serum liver injury biomarkers and decreased serum protein, globulin, and albumin. Hepatic glutathione S-transferase (GST), superoxide dismutase (SOD), thioredoxin-1 (Txn-1), and catalase (CAT) activities and gene expression were decreased and glutathione content was reduced in the TD-challenged rats, and these effects were alleviated by lycopene. Furthermore, TD induced apoptosis in liver tissues as shown by DNA fragmentation and upregulation of proapoptotic Bax and Casp-3 while lycopene upregulated the antiapoptotic Bcl-2. The results of Western blot showed that lycopene initiated low expression of mitogen activated protein kinase pathway (MAPK) protein expression in liver tissues of TD-challenged rats. In addition, lycopene reduced fatty degeneration and necrosis of the liver in TD-challenged group. Our data demonstrate that lycopene appears to be highly efficient in mitigating the hepatotoxic impacts of TD by preventing lipid peroxidation and initiating modifications in the expression and activity of antioxidant pathways. Surprisingly, lycopene fortified liver tissue by inhibiting DNA fragmentation and apoptosis signaling induced by TD. MAPK activation may be dependent from ROS generation; due to lycopene which possessed antioxidant potential did have a substantial effect on MAPK activity.

Protective Effects of Miswak (Salvadora persica) against Experimentally Induced Gastric Ulcers in Rats.

Gastric ulcers are among the most broadly perceived illnesses affecting individuals. Alcohol consumption is the main cause of gastric ulceration. This study assessed the protective effects of Salvadora persica (SP) extract against ethanol-induced gastric ulcer and elucidated the conceivable underlying mechanisms involved. For this purpose, 40 rats were allotted into 4 equal groups (control, ethanol- (EtOH-) treated, and SP-treated "SP200 and SP400" groups). The control and EtOH-treated groups were given phosphate buffer saline (PBS), and both the SP200 and SP400 groups were given SP extract dissolved in PBS at doses of 200 and 400 mg/kg b.w., respectively. All treatments were given orally for 7 constitutive days. On the 8th day, all rats were fasted for 24 h followed by oral gavage of PBS in the control group and chilled absolute ethanol solution (5 ml/kg b.w.) in the EtOH- and SP-treated groups to induce gastric lesions. One hour later, the rats were sacrificed and the stomachs were harvested. Gross and microscopic examinations of the EtOH-treated group showed severe gastric hemorrhagic necrosis, submucosal edema, destruction of epithelial cells, and reduced glycoprotein content at the mucus surface. These pathological lesions were defeated by SP extract treatment. Administration of SP extract modulated the oxidative stress and augmented the antioxidant defenses. The elevated ethanol-expressed tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) genes, as well as bcl-2-like protein 4 (Bax) and inducible nitric oxide synthase (iNOS), were diminished in the SP-treated group. Curiously, SP extract upregulated endothelial nitric oxide synthase (eNOS) and transforming growth factor-ß1 (TGF-ß1) gene expression comparable to that of the EtOH-treated rats. Aggregately, SP exerted antiulcer activities in ethanol-induced gastric ulcer rat models via modulation of oxidant/antioxidant status, mitigation of proinflammatory cytokines, and apoptosis, as well as remodeling of both NOS isoforms.

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.

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) (200mg/kg bwt, i.p twice weekly for two months); melatonin (5mg/kgbwt, 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-α, and interleukin-1ß), fibrogenic-related genes (transforming growth factor-1ß, 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.