Examining the Influence of Zinc Oxide Nanoparticles and Bulk Zinc Oxide on Rat Brain Functions: a Comprehensive Neurobehavioral, Antioxidant, Gene Expression, and Histopathological Investigation.

The study aimed to assess the impact of zinc oxide nanoparticles (ZnONPs) on rats' neurobehavior compared to bulk zinc oxide (BZnO). Thirty male Sprague-Dawley rats were randomly assigned to five groups. The control group received Tween 80 (10%), while the ZnONP groups were given ZnONPs at 5 and 10 mg/kg body weight dosages, and the bulk zinc oxide (BZnO) groups received BZnO at the same dosages. Behavioral observations, neurobehavioral examinations, and assessments of brain tissue oxidative markers, neurotransmitter levels, and histopathological changes were performed. The results indicated that ZnONP at a dosage of 5 mg/kg improved general behavior, locomotor activity, memory, and recognition and reduced fearfulness in rats. Conversely, the higher dosage of 10 mg/kg and the bulk form had adverse effects on general behavior, locomotor activity, and learning ability, with the bulk form demonstrating the most severe impact-znONP-5 treatment increased antioxidant enzyme levels and decreased inflammatory markers. BZnO-5 exhibited lower oxidative stress markers, although still higher than BZnO-10. Furthermore, ZnONP-5 and BZnO-5 increased neurotransmitter levels compared to higher dosages. ZnONP-5 upregulated the expression of brain-derived neurotrophic factor (BDNF) mRNA, while BZnO-5 showed increased BDNF mRNA expression and decreased expression of genes related to apoptosis and inflammation. In summary, ZnONPs at 5 mg/kg demonstrated positive effects on rat brain function and behavior, while higher dosages and the bulk form had detrimental effects. In conclusion, the studies emphasized the importance of further assessing various doses and forms of zinc oxide on brain health, highlighting the significance of dosage considerations when using nanomaterials.

Curcumin-infused nanostructured lipid carriers: a promising strategy for enhancing skin regeneration and combating microbial infection.

BACKGROUND: Curcumin is a biomolecule that can be extracted from the Curcuma longa that has been shown to have the potential to aid skin wound healing. It has been studied for its anti-inflammatory and antioxidant properties, which may help to reduce swelling and promote tissue repair. However, curcumin has low solubility in water, which can limit its absorption and bioavailability. Encapsulating it in lipid nanoparticles may help to increase its absorption, leading to improved bioavailability. METHODS: Curcumin-loaded nanostructure lipid nanocarriers (CURC-NLCs) were prepared and characterized. Also, the phenolic, flavonoid contents, antioxidant and antimicrobial efficacy against gram-positive and gram-negative bacteria were investigated. Furthermore, in vivo rabbit animal model was used to test its regenerative capacity and wound-healing efficiency. RESULTS: The CURC-NLCs significantly increased the content of phenolic and flavonoid compounds compared to curcumin, resulting in a dramatic increase in antioxidant activity. CURC-NLCs also showed a potent inhibitory effect on Gram-positive, Gram-negative, and fungi, two times higher than curcumin. CURC-NLCs showed a higher potential to fasten the wound healing of full-thickness skin injuries as it resulted in 1.15- and 1.9-fold higher wound closure at the first week of injury compared to curcumin and control, respectively (p < 0.0001). CONCLUSION: These results suggest that CURC-NLCs have an excellent potential to promote skin regeneration, which could be attributed to its antioxidant and broad-spectrum antimicrobial effect.

Pathological and genetic characterization of foot and mouth disease viruses collected from cattle and water buffalo in Egypt.

Foot-and-mouth disease (FMD), a highly contagious viral disease caused by FMD virus (FMDV) that threatens Egypt's livestock industry. FMDV causes severe economic losses in the livestock, with restriction of international trade from endemic regions. Surveillance for FMDV serotypes circulating in Egypt is urgently needed to assess the epidemiological situation in the country. FMD outbreaks reported in Egypt in between December 2016 and January-March 2017. A cross-sectional study was conducted to identify the FMDV serotypes responsible for the outbreaks and to collect information on the virus's morphopathological effects. Postmortem tissue and clinical samples (oral swabs, vesicular fluids from ruptured vesicles, and blood) were collected from recently deceased and infected animals. Pathological examination revealed classical FMD lesions as vesicular and erosive lesions on epithelial tissues with non-suppurative lymphoplasmacytic myocarditis. Phylogenetic and sequencing analyses demonstrated that FMDV serotype O, EA-3 topotype, VP1 is the prevalent serotype responsible for the pathological alterations and the high mortality in young calves, adult cattle, and water buffalo. The outcomes indicate continuous mutations in the circulating FMDV, which result in the occasional failure of vaccination. Based on these findings, extensive continuous monitoring and serotyping of the existing circulating FMDV isolates and regular vaccination with reevaluation of the currently used vaccine in Egypt are recommended to prevent the recurrence of such outbreaks.

Compartment 1 acidosis associated with hemorrhagic diathesis causing mortalities among racing camels in Oman.

Camels are adapted to digestion of dry rough forages for their nutrition, and sudden change to highly digestible feed during the racing season causes digestive disorders. The current study investigated the cause of death among racing dromedary camels within 3-7 days following a sudden onset of fever ≈ 41 °C, colic with tarry feces, and enlarged superficial lymph nodes. Marked leukopenia, low RBC count and thrombocytopenia, deranged liver and renal function tests, and prolonged coagulation profiles were reported. Compartment 1 fluid revealed a pH of 4.3-5.2 with absence or few ciliated protozoa and Gram-positive microbial flora. Widespread petechial to ecchymotic hemorrhages were observed in various organs including the gastrointestinal tract (compartment 3 and colon), lungs, and heart. Fibrin thrombi in arterioles, capillaries, venules, and medium-sized veins were observed especially in the pulmonary interstitium, submucosa of the large intestine (ascending colon), deep dermis, and renal cortex. Furthermore, widespread hemorrhages and necrosis were constant histopathological lesions in parenchymatous organs. Based on clinical signs, hematology, blood biochemistry, and gross and microscopical findings, the cases were diagnosed as compartment 1 acidosis associated with hemorrhagic diathesis and endotoxicosis. Finally, compartment 1 acidosis associated with hemorrhagic diathesis is a serious fatal disease on the Arabian Peninsula in racing dromedaries causing multi-organ dysfunction and coagulopathy and disseminated hemorrhages.

Ginseng® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats.

This study aims to see if Ginseng® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng® (300 mg/kg/day). Group 4 was orally given Panax Ginseng® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion's toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng® and malathion co-treatment reduced malathion's harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels.

Ornipural® Mitigates Malathion-Induced Hepato-Renal Damage in Rats via Amelioration of Oxidative Stress Biomarkers, Restoration of Antioxidant Activity, and Attenuation of Inflammatory Response.

The current study was instigated by investigating the ameliorative potential of Ornipural® solution against the hepato-renal toxicity of malathion. A total number of 35 male Wistar albino rats were divided equally into five groups. Group 1 served as control and received normal saline intraperitoneally. Group 2, the sham group, were administered only corn oil (vehicle of malathion) orally. Group 3 was orally intoxicated by malathion in corn oil at a dose of 135 mg/kg BW via intra-gastric gavage. Group 4 received malathion orally concomitantly with Ornipural® intraperitoneally. Group 5 was given Ornipural® solution in saline via intraperitoneal injection at a dose of (1 mL/kg BW). Animals received the treatment regime for 30 days. Histopathological examination revealed the harmful effect of malathion on hepatic and renal tissue. The results showed that malathion induced a significant decrease in body weight and marked elevation in the activity of liver enzymes, LDH, and ACP. In contrast, the activity of AchE and Paraoxonase was markedly decreased. Moreover, there was a significant increase in the serum content of bilirubin, cholesterol, and kidney injury markers. A significant elevation in malondialdehyde, nitric oxide (nitrite), and 8-hydroxy-2-deoxyguanosine was observed, along with a substantial reduction in antioxidant activity. Furthermore, malathion increased tumor necrosis factor-alpha, the upregulation of IL-1B, BAX, and IFN-ß genes, and the downregulation of Nrf2, Bcl2, and HO-1 genes. Concurrent administration of Ornipural® with malathion attenuated the detrimental impact of malathion through ameliorating metabolic biomarkers, restoring antioxidant activity, reducing the inflammatory response, and improving pathologic microscopic alterations. It could be concluded that Ornipural® solution demonstrates hepatorenal defensive impacts against malathion toxicity at biochemical, antioxidants, molecular, and cellular levels.

Protective potential of royal jelly against hydroxyurea -induced hepatic injury in rats via antioxidant, anti-inflammatory, and anti-apoptosis properties.

Hydroxyurea (HDU) is a widely used medication for various malignancies, thalassemia, and sickle cell anemia with reported side effects. The current study investigated HDU- induced hepatic injury and the protective potential of the royal jelly (RJ) against this hepatotoxic effect in the light of hepatic oxidative/ antioxidative status, pro-inflammatory cytokine, apoptosis signaling pathway, and histopathology. Sixty albino rats were used (n = 10/group) for 60 days: control, RJ (100 mg/kg body weight, orally), HDU (225 mg/kg body weight, orally), 2HDU (450 mg/kg body weight, orally), and HDU + RJ groups. HDU-treated rats showed significant elevation of liver function tests as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, as well as malondialdehyde and nitric oxide (oxidative biomarkers) and significant decreased hepatic antioxidant molecules (reduced glutathione, superoxide dismutase, and glutathione peroxidase), compared to a control group, that more pronounced in the high dose of HDU. In addition, HDU induced significant upregulation of TNF-α and the Caspase-3 apoptotic pathway. Moreover, the liver of HDU treated groups showed various hepatic lesions from mild to severe necrotic changes related to the HDU dose. However, administration of RJ with HDU improved liver function tests, liver histology, and hepatic oxidative/antioxidative status concerning HDU groups. Furthermore, oral RJ administration with HDU significantly lessens the immune-expression area % of TNF-α and Caspase-3. Thus, the royal jelly has antioxidant, anti-inflammatory, and anti-apoptotic properties against HDU- induced hepatic injury and could be, therefore, used as adjuvant therapy in patients with long-term HDU medication.

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.

Hepatorenal protective effect of nano-curcumin against nano­copper oxide-mediated toxicity in rats: Behavioral performance, antioxidant, anti-inflammatory, apoptosis, and histopathology.

BACKGROUND: Metal oxide nanoparticles (NPs) induce oxidative stress that can cause cellular toxicity. A natural antioxidant that can be used to protect tissues from oxidative stress is curcumin. PURPOSE: In the present study, we evaluated the protective effect of curcumin nanoparticles (curcumin-NPs) against copper oxide nanoparticles (CuO-NPs)-mediated hepatorenal effects on behavioral performance, biochemical markers, antioxidants, inflammation, apoptosis, and histopathology in rats. STUDY DESIGN: Twenty Wistar adult male rats were randomly divided into four groups (n = 5); Group Ι served as a control, group ΙΙ was orally gavaged with curcumin-NPs (100 mg/Kg), group ΙΙI orally received CuO-NPs (100 mg/kg), and group ΙV received both CuO-NPs and curcumin-NPs orally for 14 days. METHODS: Behavioral performance, biochemical markers, antioxidants, inflammatory mediators, and apoptotic gene expression were evaluated in addition to histopathological and immunohistochemical examination. RESULTS: The results revealed that rats exposed to CuO-NPs suffered from behavioral alterations and hepatic and renal damages, which indicated by a marked elevation of serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, urea, uric acid, and creatinine and a decline of total protein. Moreover, there was a significant downregulation in the expression of antioxidants genes, whereas inflammatory mediators expression were upregulated. The histopathological and immunohistochemical examination also corroborated these findings. In contrast, rats co-treated with curcumin-NPs exhibited better behavioral performance, biochemical profile, gene expression, histological architecture, and immunohistochemical staining results. CONCLUSION: These findings strongly indicated that curcumin-NPs exert significant protection against the behavioral and hepatorenal disorders induced by CuO-NPs toxicity by modulating oxidative stress regulators and gene expression.

Assessment of reproductive toxicity of carbofuran and copper sulfate in male Nile tilapia (Oreochromis niloticus).

This study's hypothesis is that carbofuran and copper sulfate have a synergistic harmful impact on the fertility of male Nile tilapia. Hence, this study was designed to assess the toxic reproductive outcome of carbofuran, copper sulfate, and their mixture in male Nile tilapia. Sixty male Nile tilapia fishes were separated into four groups (15 fish/group). The control group; carbofuran group, was given dechlorinated tap water containing 0.02 mg/L (1/10 dose of LC50) carbofuran; copper group was given dechlorinated tap water containing 4.0 mg/L (1/10 dose of LC50) copper sulfate; carbofuran + copper sulfate group received dechlorinated tap water containing 0.02 mg/L carbofuran plus 4.0 mg/L copper sulfate. After 6 weeks, results revealed a significant rise in testicular malondialdehyde levels and a significant decrease in testicular reduced glutathione contents among all experimental groups compared to the control group. Testicular testosterone levels were significantly declined in copper and combined groups compared to the control. The seminal evaluation using computer-assisted sperm analysis showed a significant decline in the progressive motility percentage, motile ratio percentage, sperm concentration, curvilinear velocity, straight-line velocity, average path velocity, and wobble in all intoxicated groups, particularly, the combined group. The histopathology of testes in all intoxicated groups revealed a detachment of the basal membrane of some seminiferous tubules, and others were free from spermatogonia and spermatozoa with interstitial eosinophilic granular cell infiltration. Testicular lesions were more severe in the combined group. Finally, it was concluded that carbofuran and copper sulfate exerted a negative effect on the reproductive function of male Nile tilapia, and they have a synergistic harmful impact on the fertility of male Nile tilapia.

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.

Ameliorative Effects of Boswellic Acid on Fipronil-Induced Toxicity: Antioxidant State, Apoptotic Markers, and Testicular Steroidogenic Expression in Male Rats.

The study investigated the ability of boswellic acid (BA) to alleviate the testicular and oxidative injury FPN insecticide intoxication in the male rat model. Rats were randomly assigned to six equivalent groups (six rats each) as the following: control rats orally administered with 2 mL physiological saline/kg of body weight (bwt); boswellic acid (BA1) rats orally administered 250 mg BA/kg bwt; boswellic acid (BA2) rats orally administered 500 mg BA/kg bwt; fipronil (FPN) rats orally administered 20 mg FPN/kg bwt; (FPN + BA1) rats orally administered 20 mg FPN/kg bwt plus 250 mg BA/kg bwt, and (FPN + BA2) rats orally administered 20 mg FPN/kg bwt plus 500 mg BA/kg bwt. After 60 days, semen viability percentage and live spermatozoa percentage were decreased, and a considerably increased abnormality of the sperm cells in FPN-administered rats improved substantially with the co-administration of BA. BA had refinement of the histological architecture of testes and sexual glands. Quantitative analysis recorded a noticeable decline in the nuclear cell-proliferating antigen (PCNA) percentage area. FPN triggered cell damage, which was suggested by elevated malondialdehyde and interleukin 6, tumor necrosis factors alpha, and decreased glutathione level. Proapoptotic factor overexpression is mediated by FPN administration, while it decreased the antiapoptotic protein expression. Similarly, BA has shown significant upregulation in steroidogenic and fertility-related gene expression concerning the FPN group. Pathophysiological damages induced by FPN could be alleviated by BA's antioxidant ability and antiapoptotic factor alongside the upregulation of steroidogenic and fertility-related genes and regimented the detrimental effects of FPN on antioxidant and pro-inflammatory biomarkers.

Protective effect of methylene blue against copper oxide nanoparticle-induced neurobehavioral toxicity.

Increasing attention has been paid in the past decade to assessing the toxicological effects of nanoparticles and finding a protectant; thus, the current study aimed to investigate the protective effect of the mitochondria-targeting drug methylene blue (MB) against copper oxide nanoparticle (CuO-NP)-induced neurobehavioral toxicity in rats. For this purpose, twenty rats were allocated to four equal groups (n = 5). The negative control group received distilled water intraperitoneally (IP) and Tween 80 (10 %) orally. The CuO-NP group was given a dose of 100 mg/kg of CuO-NPs, administered orally, and the positive control group was treated with 1 mg/kg MB intraperitoneally (IP). The final group was concurrently exposed to CuO-NPs and MB for 14 consecutive days. At the end of the study, each group was neurobehaviorally blind tested relative to other experimental animals, then brain tissue markers were determined and a histopathological examination was conducted. The results showed that supplementation with CuO-NPs induced neurobehavioral alterations; increased Cu content in the brain; and enhanced lipid peroxidation (malondialdehyde [MDA]), protein peroxidation (protein carbonyl [PC]), and DNA oxidative damage (8-hydroxy-2-deoxyguanosine [8-OH-dG]) compared to other treatments. In addition, a decrease was noted in the mitochondrial dehydrogenases' (aldehyde dehydrogenase 2 [ALDH2], and glutamate dehydrogenase [GDH]) activity in Cu-exposed rats. The histopathological findings revealed shrunken, pyknotic, and hypereosinophic cortical neurons and increased immune positive brown staining of caspase-3 protein, indicating apoptosis. Co-treatment with methylene blue ameliorated the neurotoxic effects of CuO-NPs; therefore, MB evidently had a powerful modulatory effect against the neurotoxicity of nano-Cu oxide via its antioxidant and mitochondrial protection properties.

Ameliorative Effect of Graviola (Annona muricata) on Mono Sodium Glutamate-Induced Hepatic Injury in Rats: Antioxidant, Apoptotic, Anti-inflammatory, Lipogenesis Markers, and Histopathological Studies.

Monosodium glutamate (MSG) is a widely used food additive, and there is a trepidation that MSG plays a critical role in multiple hepatic disorders. This study was planned to investigate Graviola extract (GE) effects on hepatic and cellular alterations induced by MSG. Fifty Wistar rats were randomly allocated into five groups: control (received normal saline), Graviola (received 200 mg/kg body weight), MSG (received 2.4 gm MSG/kg, 15% of Lethal dose (LD50) of MSG), Graviola + monosodium glutamate (MSG + GE; received GE, 200 mg/kg/day and MSG 2.4 gm/kg body weight (BW) for the next four weeks), and monosodium glutamate + Graviola (received MSG only (2.4 gm/kg BW) daily for four weeks, then concomitant with Graviola (200 mg/kg BW) daily for the next four weeks. MSG and GR were administered orally for eight weeks. Our results showed that MSG caused a significant increase in oxidative stress markers malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), hydrogen peroxide (H2O2), proinflammatory cytokines interleukin 6 (IL-6) level, a tumor protein (P53), hepatic cellular damage, as well as proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). A significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (BCl-2) was observed. The detected MSG effects were normalized by Graviola administration, either a prophylactic or protecting dose. Besides, Graviola reduced the expression of inducible nitric oxide synthase (iNOS) and hepatic fatty acid synthase (FAS) and led to the upregulation of the silent information regulator protein one gene expression gene (SIRT1).In conclusion, the results suggest that Gaviola's interrelated antiapoptotic, antioxidant, and anti-inflammatory properties are potential mechanisms to enhance hepatic deficits and protect the liver. Graviola can, therefore, be considered a promising hepatoprotective supplement. Additionally, further human clinical trials are also necessary to validate the present research.

Insight Study on the Comparison between Zinc Oxide Nanoparticles and Its Bulk Impact on Reproductive Performance, Antioxidant Levels, Gene Expression, and Histopathology of Testes in Male Rats.

Background: Despite the beneficial effects of zinc oxide nanoparticles (ZnONPs) on different biomedical applications, including their antioxidant and anti-inflammatory ones, it might have cytotoxic and genotoxic impacts on the male reproductive system. Objective: The current study compares the effect of zinc oxide nanoparticles and their bulk form, at different doses, on male rats' reproductive performance, testicular antioxidants, gene expression, and histopathology. Materials and Methods: Thirty male rats were randomly allocated equally in five groups. The control one was injected with Tween 80 (10%). The zinc oxide nanoparticle (ZnONP) groups received ZnONPs < 50 nm, specifically, 5 mg/kg (ZnONP-1) and 10 mg/kg (ZnONP-2). The bulk zinc oxide (BZnO) groups were administered 5 mg/kg (BZnO-1) and 10 mg/kg (BZnO-2), correspondingly. Rats were injected intraperitoneally with the respected materials, twice/week for eight consecutive weeks. Finally, the male rats' sexual behavior and their pup's performance were determined in a monogamous mating system. Rats were then anesthetized and sacrificed for semen characteristics evaluation and tissue collection for antioxidant and hormones analysis, gene expression, and histopathological examination. Results: It was shown that ZnONP-1 improved sexual behavior, semen characteristics, and pup's performance compared to its bulk form. Similarly, the testicular antioxidants activity, glutathione (GSH), and superoxide dismutase (SOD) increased with a decrease in the malonaldehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. It also improves the reproductive hormone levels and mRNA expression of different steroidogenesis-associated genes and anti-apoptotic genes. Conclusion: It can be concluded that zinc oxide nanoparticles, administered at 5 mg/kg, had the most beneficial effect on male reproductive performance, while 10 mg/kg could have a detrimental effect.

Attenuation potentials of royal jelly against hydroxyurea-induced infertility through inhibiting oxidation and release of pro-inflammatory cytokines in male rats.

Hydroxyurea (HDU), a class of antineoplastic drugs, has a powerful efficacy in the treatment of several types of malignancies. However, it has multiple adverse effects including reduced fertility, especially in males. Thus, 60 male albino rats were used to investigate the chemoprotective potentials of royal jelly on HDU-induced testicular damage. Animals were gastro-gavaged with HDU (225 or 450 mg kg-1 bw day-1) before royal jelly (100 mg kg-1 bw day-1) for 60 days. Blood samples and testicles were collected, and spermatozoon was obtained. In a dose-dependent manner, the sperm count, motility and liveability, and testosterone, GSH, and catalase concentrations were decreased in HDU groups, whereas MDA, FSH, LH, IL-6, and IFN-γ expression levels were increased. Germinal epithelium degeneration, germ cell sloughing, reduction in the number of luminal spermatozoa, interstitial congestion, and severe leukocyte infiltration besides no glandular secretion in most of the acini were identified. However, royal jelly intake in HDU-treated rats successfully improved sperm quality, hormonal and antioxidant status, and reproductive organ histoarchitecture. Thus, it could be concluded that royal jelly is endowed with antioxidative and anti-inflammatory activities and could be, therefore, used as an adjuvant remedy to improve HDU-induced male subfertility.

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.

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.

Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status.

Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines.