Immuno-antioxidative reno-modulatory effectiveness of Echinacea purpurea extract against bifenthrin-induced renal poisoning.

This study was conducted to evaluate the ameliorative, anti-inflammatory, antioxidant, and chemical detoxifying activities of Echinacea purpurea ethanolic extract (EEE) against bifenthrin-induced renal injury. Adult male albino rats (160-200 g) were divided into four groups (10 rats each) and orally treated for 30 days as follows: (1) normal control; (2) healthy animals were treated with EEE (465 mg/kg/day) dissolved in water; (3) healthy animals were given bifenthrin (7 mg/kg/day) dissolved in olive oil; (4) animals were orally administered with EEE 1-h prior bifenthrin intoxication. The obtained results revealed that administration of the animals with bifenthrin caused significant elevations of serum values of urea, creatinine, ALAT and ASAT, as well as renal inflammatory (IL-1ß, TNF-α & IFN-γ), apoptotic (Caspase-3) and oxidative stress (MDA and NO) markers coupled with a marked drop in the values of renal antioxidant markers (GSH, GPx, and SOD) in compare to those of normal control. Administration of EEE prior to bifenthrin resulted in a considerable amelioration of the mentioned deteriorated parameters near to that of control; moreover, the extract markedly improved the histological architecture of the kidney. In conclusion, Echinacea purpurea ethanolic extract has promising ameliorative, antioxidant, anti-inflammatory, renoprotective, and detoxifying efficiencies against bifenthrin-induced renal injury.

Echinacea purpurea extract intervention for counteracting neurochemical and behavioral changes induced by bifenthrin.

This study was conducted to elucidate the possible protective efficiency of Echinacea purpurea hydroethanolic extract (EchEE) against bifenthrin (BIF)-induced neuro-chemical and behavioral changes in rats. Total phenolics content, reducing power and radical scavenging activity of EchEE were estimated. Four groups of adult male albino rats were used (10 rats each) as follows: 1) Control healthy rats ingested with placebo, 2) Healthy rats orally received EchEE (465 mg/kg/day), 3) Rats intoxicated with BIF (7mg/kg/day) dissolved in olive oil, and 4) Rats co-treated with EchEE (465 mg/kg/day) besides to BIF (7mg/kg/day) intoxication. After 30 days, some neuro-chemical and behavioral tests were assessed. The behavioral tests revealed that rats received BIF exhibited exploratory behavior and spatial learning impairments, memory and locomotion dysfunction, and enhanced anxiety level. Biochemical findings revealed that BIF induced-oxidative stress in the cortex and hippocampus; this was appeared from the significant rise in malondialdehyde (MDA) and nitric oxide (NO) levels, coupled with decreased catalase (CAT), superoxide dismutase (SOD), paraoxonase-1 (PON-1) activities, and reduced glutathione (GSH) level in both brain areas. Also, BIF induced a significant increase caspas-3, tumor necrosis factor alpha (TNF), and interleukin-1beta (IL-1ß) in both areas; dopamine and serotonin levels, and ACh-ase activity were markedly decreased in both areas. Interestingly, treatment of rats with EchEE in combination with BIF resulted in a significant decrease in oxidative stress damage, and modulation of the apoptotic and pro-inflammatory markers. Also, EchEE markedly improved behavioral activities and neurotransmitters level that were impaired by BIF. In conclusion, the present study clearly indicated that EchEE can attenuate brain dysfunction induced by pesticides exposure through preventing the oxidative stress. This may be attributed to its high antioxidant component.

Green synthesis, characterization, anti-SARS-CoV-2 entry, and replication of lactoferrin-coated zinc nanoparticles with halting lung fibrosis induced in adult male albino rats.

The ethanolic extract of Coleus forskohlii Briq leaves was employed in the green synthesis of zinc nanoparticles (Zn-NPs) by an immediate, one-step, and cost-effective method in the present study. Zn-NPs were coated with purified bovine lactoferrin (LF) and characterized through different instrumental analysis. The biosynthesized Zn-NPs were white in color revealing oval to spherical-shaped particles with an average size of 77 ± 5.50 nm, whereas LF-coated Zn-NPs (LF-Zn-NPs) revealed a larger particles size of up to 98 ± 6.40 nm. The biosynthesized Zn-NPs and LF-Zn-NPs revealed negatively charged surfaces with zeta-potentials of - 20.25 ± 0.35 and - 44.3 ± 3.25 mV, respectively. Interestingly, the LF-Zn-NPs showed potent in vitro retardation for SARS-CoV-2 entry to host cells by binding to the ACE2-receptor and spike protein receptor binding domain at IC50 values of 59.66 and µg/mL, respectively. Additionally, the results indicated the ability of LF-Zn-NPs to inhibit SARS-CoV-2 replication by interfering with RNA-dependent RNA polymerase "RdRp" activity at IC50 of 49.23 µg/mL. In vivo, the LF-Zn-NPs displayed a protective and therapeutic activity against induced pulmonary fibrosis in Bleomycin-treated male albino rats owing to its anti-inflammatory, antioxidant, and significant reduction in CRP, LDH, ferritin, and D-dimer levels. The obtained findings offer a promising route for biosynthesized Zn-NPs and LF-Zn-NPs as promising candidates against COVID-19.

In Vitro and In Vivo Synergistic Antitumor Activity of Albumin-Coated Oleic Acid-Loaded Liposomes toward Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers, closely associated with cirrhosis and fibrosis. This study aimed to assess the antitumor activity of oleic acid-liposomes (uncoated liposomes) upon coating with albumin against HCC. The in vitro studies revealed the high safety of the prepared uncoated and albumin-coated liposomes to normal HFB-4 cells (EC100 of 35.57 ± 0.17 and 79.133 ± 2.92 µM, respectively) with significant anticancer activity against HepG-2 cells with IC50 of 56.29 ± 0.91 and 26.74 ± 0.64 µM, respectively. The albumin-coated liposomes revealed superior apoptosis induction potential (80.7%) with significant upregulation of p53 gene expression (>7.0-fold), compared to OA. The in vivo study revealed that the administration of uncoated or albumin-coated liposomes (100 mg/kg) for six weeks markedly retarded the DENA-induced HCC in Wistar albino rates through regulating the liver enzymes, total bilirubin level, pro-inflammatory cytokines, and oxidative stress. Accordingly, the current study supports the in vitro and in vivo chemo-preventive feature of albumin-coated liposomes against HCC through modulation of apoptosis, improvement of the immune response, reduction of inflammation, and restoration of impaired oxidative stress, which is the first reported to the best of our knowledge.

Inhibitory effect of lactoferrin-coated zinc nanoparticles on SARS-CoV-2 replication and entry along with improvement of lung fibrosis induced in adult male albino rats.

Severe acute respiratory syndrome 2019-new coronavirus (SARS-CoV-2) is a major global challenge caused by a pandemic disease, named 'COVID-19' with no effective and selective therapy available so far. COVID-19-associated mortality is directly related to the inability to suppress the viral infection and the uncontrolled inflammatory response. So, we investigated the antiviral efficiency of the nanofabricated and well-characterized lactoferrin-coated zinc nanoparticles (Lf-Zn-NPs) on SARS-CoV-2 replication and entry into host cells. Lf-Zn-NPs showed potent inhibition of the entry of SARS-CoV-2 into the host cells by inhibition of ACE2, the SARS-CoV-2 receptor. This inhibitory activity of Lf-Zn-NPs to target the interaction between the SARS-CoV-2 spike protein and the ACE2 receptor offers potent protection against COVID-19 outbreaks. Moreover, the administration of Lf-Zn-NPs markedly improved lung fibrosis disorders, as supported by histopathological findings and monitored by the significant reduction in the values of CRP, LDH, ferritin, and D-dimer, with a remarkable rise in CD4+, lung SOD, GPx, GSH, and CAT levels. Lf-Zn-NPs revealed therapeutic efficiency against lung fibrosis owing to their anti-inflammatory, antioxidant, and ACE2-inhibiting activities. These findings suggest a promising nanomedicine agent against COVID-19 and its complications, with improved antiviral and immunomodulatory properties as well as a safer mode of action.

Hormonal and inflammatory modulatory effects of hesperidin in hyperthyroidism-modeled rats.

The goal of the current study was to investigate the hormonal modulatory efficiency of hesperidin, through its regulatory potential of immunological, inflammatory, and/or antioxidant changes in on hyperthyroidism modeled adult female albino rats. Both normal and hyperthyroidism modeled rats (140-160g) were randomly divided into four groups (10 animals each) as follows: 1) healthy animals were daily ingested with saline for six weeks, and served as control group, 2) healthy animals were intraperitoneally injected with hesperidin (50 mg/kg/day) for a similar period, 3) hyperthyroidism-modeled animals without any treatment acted as positive control, and 4) hyperthyroidism-modeled animals were treated intraperitoneally with hesperidin for a similar period. The findings showed that hesperidin significantly modulated hyperthyroidism deteriorations, this was evidenced by a remarkable decline in serum T4, FT4, T3, FT3, TNF-α, IL1ß-, IL4-, IL-6, and IL-10 levels, with a minor increase in TSH and significant raise in CD4+ level. Similarly, valuable improvement was observed in the oxidative status; serum SOD, GPx, CAT, and GSH levels were dramatically enhanced, associated with remarkable drop in MDA and NO levels. Also, hesperidin demonstrated nephro-hepatoprotective and anti-atherogenic potential, this was achieved from the notable reduction in ALAT and ASAT activities as well as urea, creatinine, cholesterol, and triglyceride close to the corresponding values of healthy group. These findings were supported by histological and immunohistochemical ones that showed a notable decrease in the expression of the calcitonin antibody. In conclusion, hesperidin possesses anti-hyperthyroidism, immunoinflammatory regulatory, and antioxidant activities that evidenced from the improvement of physio-architecture of the thyroid gland, reduction of inflammation and restoration of the impaired oxidative stress. This effect might be mechanized through immunological, inflammatory, apoptotic, and/or antioxidant modulatory pathways.

Modulatory Efficiency of LP/LF Nano-Combination on Neurochemical and Behavioural Retardations in the Brain of Induced-Epileptic Rats.

<b>Background and Objective:</b> Epilepsy is one of the normal neurological problems that came about because of strange electrical movements and prompt serious and far-reaching cell misfortune in the mind. This study aimed to investigate if a nano-Chitosan formulation loaded with bovine milk lactoperoxidase (LPO) and lactoferrin (LF) could prevent Lithium Chloride/Pilocarpine-induced epilepsy in rats or not. <b>Materials and Methods:</b> Adult male rats (200-250 g) were partitioned into four groups (8 animals each) as follows: Group (1) Normal rats served as control group and received saline orally, group (2) Normal rats ingested with a daily oral dose of LPO and LF-NPS formulation at 50 mg kg¹, group (3) Pilocarpine-induced epileptic rats and group (4) Epilepsy-modeled rats were treated with LPO+LF NPs (50 mg/kg/day, orally) for 6 weeks. <b>Results:</b> The results revealed that the administration of LPO+LF-NPs markedly improved the induced-epilepsy disorders, this was monitored from the significant reduction in the values of caspase-3, TNF-α, IL-1ß, CD4⁺, MDA and NO coupled with remarkable raise in AchE-ase, dopamine, serotonin, SOD and GPx, CAT and GSH values in both brain regions. <b>Conclusion:</b> This study supported the anti-epilepsy features of LPO+LF-NPS against Lithium Chloride/Pilocarpine-induced epilepsy in rats through the improvement of the immune response, reduction of inflammation and restoration of the impaired oxidative stress status.

The Antioxidant and Antitumor Efficiency of Litophyton sp. Extract in DMH-Induced Colon Cancer in Male Rats.

One of the most common tumors to cause death worldwide is colon cancer. This study aims to investigate the antitumor potency of Litophyton sp. methanolic extract (LME) against DMH-induced colon cancer in adult male rats. Group (1) normal rats served as the control, group (2) normal rats were ip-injected with LME at a dose of 100 µg/kg/day, group (3) DMH-induced colon cancer animals, and group (4) colon cancer-modeled animals were treated with LME (100 µg/kg/day) for six weeks. The results revealed that injection of LME markedly regenerated the colon cancer pathophysiological disorders; this was monitored from the significant reduction in the values of serum biomarkers (CEA, CA19.9, AFP), cytokines (TNF-α and IL1ß), and biochemical measurements (ALAT, ASAT, urea, creatinine, cholesterol, and triglycerides) matched significant increase of apoptotic biomarkers (CD4+); similarly, colon DNA fragmentation, MDA, and NO levels were down-regulated. In contrast, a remarkable upregulation in colon SOD, GPx, GSH, and CAT levels was noted. Moreover, the colon histopathological architecture showed obvious regenerations. Chromatography of LME resulted in the purification of two polyhydroxylated steroids (1 and 2) with potential cytotoxic activities. LME performed therapeutic potential colon tumorigenesis; therefore, LME may have a promising chemo-preventive feature against colon cancer, probably via enhancement of the apoptosis pathway, improvement of the immune response, reduction of inflammation, or/and restoration of the impaired oxidative stress.

Therapeutic efficacy of Nano-formulation of lactoperoxidase and lactoferrin via promoting immunomodulatory and apoptotic effects.

This study identifies promising potential of a novel and safer nanocombination of bovine milk lactoperoxidase (LPO) and lactoferrin (LF) to target breast cancer in vitro and in adult female albino rat model. Favorable selective anticancer effects of the prepared nanocombination were observed, in a dose-dependent manner, against both MCF-7 and MDA cell lines, sparing normal HFB-4 cells. The administration of LPO + LFNPs markedly improved the induced-breast cancer disorders, prolonged survival and reduced the values of serum TNF-α, IL1ß, CD4+, ALAT, ASAT, urea, creatinine, cholesterol and triglycerides with remarkable elevation in mammary SOD and GPx activity and GSH level. Moreover, the histopathological findings showed that LPO + LFNPs succeeded in prevention of mammary gland tumorigenesis. Superior efficacy of LPO + LFNPs was observed against pro-inflammatory cytokines through their anti-inflammatory and immunomodulatory properties. The treatment of LPO + LFNPs more significantly modulated the apoptosis and enhanced the expression of cell cycle regulator genes, which demonstrates a successful tumor therapy in vitro and in vivo. Therefore, this study provided evidence that the chemo-preventive feature of LPO + LFNPs may offer a novel alternative therapy for the treatment of breast cancer through enhances apoptosis pathway, improvement of immune response, reduction of inflammation and restoration of the impaired oxidative stress.

Nephroprotective Effect of Costus (Saussurea costus) Ethanolic Extract on Oxaliplatin®-induced Nephrotoxicity in Adult Male Wistar Rats.

<b>Background and Objective:</b> Oxaliplatin^® is an antineoplastic platinum-based compound; nephrotoxicity is one of its most serious side effects. This study aimed to explore the nephroprotective potential of Costus Ethanolic Extract (CEE) against Oxaliplatin^®-induced nephrotoxicity. <b>Materials and Methods:</b> Adult male Wistar rats, weighting 140-160 g, were randomly divided into four groups: (1) Normal rats, (2) Rats ingested with CEE (67.08 mg kg¹ day¹), (3) Rats injected (ip) with Oxaliplatin^® (10 mg kg¹ week¹) and (4) rats treated with CEE in combination Oxaliplatin^® injection. <b>Results:</b> After six weeks of treatments, the results revealed that CEE ingestion along with Oxaliplatin^® injection markedly minimized the Oxaliplatin^®-induced renal deterioration; this was evidenced by the significant reduction in serum urea, creatinine, uric acid, Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1Beta (IL¹ß) and Sodium ion (Na⁺) levels as well as kidney Malondialdehyde (MDA), Nitric Oxide (NO) and DNA fragmentation values. Controversially, a marked rise in serum Calcium, Potassium Ion (K⁺) and Cluster of Differentiation 4 (CD4) levels besides renal Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase (SOD) values. Similarly, the histopathological findings confirmed the biochemical ones as the CEE restored the Oxaliplatin^®-induced histological degenerations. <b>Conclusion:</b> In conclusion, CEE exhibited nephron-protection efficiency against Oxaliplatin^®-induced nephrotoxicity; this promising effect may be achieved through the antioxidant and radical scavenging activities of its constituents.

Evaluation of carcinogenic activities and sperm abnormalities of Gram-negative bacterial metabolites isolated from cancer patients after subcutaneous injection in albino rats.

Microbial pathogens drive tumorigenesis in 20% of cancer cases, so the present study is aimed to evaluate the carcinogenic activities, sperm abnormalities and other dangerous effects of the subcutaneous injection of extracts obtained from various clinical Gram-negative bacteria derived from cancer patients using albino rats. We isolated, identified and extracted of their secondary metabolites of carbapenem resistant Gram-negative bacteria derived from cancer patients. Various methods have been used to determine hepatotoxicity, nephrotoxicity, tumorigenesis, inflammatory and sperm abnormalities in the albino rats injected with extracts. In comparison with the normal animals group, all extracts induced hepatotoxicity which was evidenced by the significant elevation in the activity of the serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and alkaline phosphatase; also, nephrotoxicity that was indicated through the marked increase in the serum urea and creatinine levels; tumorigenesis was achieved from the sharp elevation in serum levels of alpha fetoprotein, carcinoembryonic antigen and lactate dehydrogenase values as tumor markers; as well as severe inflammatory characteristics were monitored from the marked raise of tumor necrosis factor alpha and interleukin-1beta. Furthermore, the proportion of micronuclei in polychromatic erythrocytes and sperm abnormalities were statistically significant in all groups compared to control group. Various kinds of head abnormalities and coiled tail were noted. Histopathological examination of hepatic tissue came in line with the biochemical and cytological findings. It could conclude that the extracts of Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 were able to initiate cytotoxicity and tumorigenesis in rats.

Neuroprotective Effect of Ashwagandha Extract against the Neurochemical Changes Induced in Rat Model of Hypothyroidism.

The current aim is to evaluate the effect of ashwagandha root extract (AE) on the neurochemical changes induced in the cortex and hippocampus as a consequence of thyroid dysfunction induced by propylthiouracil (PTU). Male Wistar rats were divided into; control, AE treated rats, rat model of hypothyroidism and rat model of hypothyroidism treated with either AE or L-thyroxine (T4) for 1 month. Rat model of hypothyroidism showed a significant decrease in serum levels of tri-iodothyronine (T3) and T4 and a significant increase in cortical and hippocampal lipid peroxidation (MDA), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT). However, reduced glutathione (GSH) decreased significantly. This was associated with a significant increase in hippocampal tumor necrosis factor-α (TNF-α) and cortical dopamine levels. Both L-thyroxine and AE restored T3 and T4 levels. In the hippocampus L-Thyroxine prevented the increase in MDA and restored GSH but failed to restore the increased NO and TNF-α. In the cortex L-thyroxine didn't change the increased MDA and NO and the decreased GSH induced by PTU. L-thyroxine increased cortical and hippocampal SOD and CAT. AE prevented the increased hippocampal MDA, NO and TNF-α and the decreased GSH level induced by PTU. In the cortex AE failed to restore MDA and NO but prevented the decrease in GSH. The increase in cortical dopamine level induced by PTU was ameliorated by L-thyroxine and improved by AE. The present data indicate that AE could prevent thyroid dysfunction and reduce its complications on the nervous system including oxidative stress and neuroinflammation.

The Anti-Diabetic Effect of Some Plant Extracts Against Streptozotocin - Induced Diabetes Type 2 in Male Albino Rats.

BACKGROUND: One of the widely spread disorders is Diabetes mellitus, especially type 2 (T2DM). T2DM is attributed to the change in life style and stress. A possible strategy to block dietary carbohydrate absorption is regulation of postprandial blood glucose level as well, the use of some natural plant extracts with inhibitory effect against carbohydrate digestive enzymes such as alpha- amylase and fewer side effects than synthetic drugs. This study was conducted to investigate the anti-diabetic effect of Cinnamon and Saussurea extract, individually, on blood glucose, lipid profile, insulin, interleukin1-beta and weight loss in diabetic rats treated with Streptozotocin (STZ). METHODS: The experiment was performed on 60 Wistar male rats; the experimental study include 6 groups (10 rats each): (I) normal rats, (II) Streptozotocin- induced diabetic rats, (III) normal rats orally received (200 mg/kg/day) Saussurea ethanolic extract (SEE) for consecutive 4 weeks, (IV) normal rats orally received (100mg/kg/day) Cinnamon aqueous extract (CAE) for consecutive 4 weeks, (V) Streptozotocin -treated rats received SEE orally (200mg /kg/ day) for consecutive 4 weeks, and (VI) Streptozotocin -treated rats received CAE orally (100mg /kg/ day) for consecutive 4 weeks. RESULTS: The results of the following study revealed that SEE has more anti-diabetic effect against Streptozotocin treatment than CAE due to the high α-amylase inhibition potential and higher phenolic content. Also, GC-MS analysis of SEE exhibited higher concentrations of phenolic compounds such as: dehydrocostus lactone, azuleno, eicosa-pentaenoic acid and linoelaidic acid that revealed anti-diabetic, anti-lipidemic and anti-inflammatory activities, while CAE showed the presence of cinnamic and quinic acids. Injection of STZ resulted in a decline in the insulin, high density lipoprotein and body weight values matched with the increase in glucose, total cholesterol, LDL-Cholesterol, triglycerides and interleukin1- ß (IL-1ß). The administration of extracts of SEE and CAE into STZ-treated rats separately resulted in a decline in the elevated levels of blood glucose, total cholesterol, triglycerides and improving serum HDL-Cholesterol and body weight. CONCLUSION: Both tested herbal extracts performed anti-diabetic effect that mainly could be mechanized via the α-amylase- inhibitory potentials due to the high phenolic and flavonoids content.

Role of ashwagandha methanolic extract in the regulation of thyroid profile in hypothyroidism modeled rats.

This study aimed to evaluate the anti-hypothyroidism potential of ashwagandha methanolic extract (AME). This target was performed through induction of animal model of hypothyroidism by propylthiouracil. After 1 month from treatments, blood samples were collected for biochemical determinations, and liver and kidney were removed for the determination of oxidative stress markers and thyroid gland was removed for histopathological examination. The total phenolic compounds in the extract and the in vitro radical scavenging activity of extract were also determined. The results revealed that the induction of hypothyroidism by propylthiouracil induced a significant increase in serum TSH level but it induced significant decreases in the levels of total T3, free T3, free T4, and total T4 hormones compared with the control values. Also, serum glucose, Il-6, and body weight gain increased significantly while Il-10 and blood hemoglobin levels showed significant decrease. Induction of hypothyroidism increased also the levels of hepatic and renal MDA and NO and decreased significantly the values of GSH, GPx and Na+/ K+-ATPase. Both AME and the anti-hypothyroidism drug significantly ameliorated the changes occurred in the levels of the above parameters and improved histological picture of thyroid gland but with different degrees; where ashwagandha methanolic extract showed the strongest effect. We can conclude that ashwagandha methanolic extract treatment improves thyroid function by ameliorating thyroid hormones and by preventing oxidative stress.

Encapsulation of cinnamon essential oil in whey protein enhances the protective effect against single or combined sub-chronic toxicity of fumonisin B1 and/or aflatoxin B1 in rats.

Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are fungal metabolites that frequently co-occur in foodstuffs and are responsible for mycotoxicosis and several primary cancers. Cinnamon essential oil (CEO) has a spacious range of benefit effects but also has some limitations owing to its strong taste or its interaction with some drugs. This study aimed to use the cinnamon oil emulsion droplets (COED) for the protection against oxidative stress, cytotoxicity, and reproductive toxicity in male Sprague-Dawley rats sub-chronically exposed to FB1 and/or AFB1. The composition of CEO was identified using GC-MS then was encapsulated using whey protein as wall material. Male rats were divided into eight groups and treated orally for 8 weeks as follows: control group, AFB1-trreated group (80 µg/kg b.w), FB1-treated group (100 mg/kg b.w), FB1 plus AFB1-treated group, and the groups treated with COED plus FB1 and/or AFB1. Blood and samples of the kidney, liver, and testis were collected for different analysis and histopathological examination. The GC-MS analysis revealed that cinnamaldehyde, α-copaene, trans-cinnamaldehyde, caryophyllene, and delta-cadinene were the main compounds in COE. The average size of COED was 235 ± 1.4 nm and the zeta potential was - 6.24 ± 0.56. Treatment with FB1 and/or AFB1 induced significant disturbances in the serum biochemical analysis, oxidative stress parameters, DNA fragmentation, gene expression, and testosterone and severe pathological changes in the tested organs. Moreover, treatment with both mycotoxins induced synergistic toxic effects. COED did not induce toxic effects and could normalize the majority of the tested parameters and improve the histological picture in rats treated with FB1 and/or AFB1. It could be concluded that COED induce potential protective effects against the single or combined exposure to FB1 and AFB1.

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1ß, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), urea, and creatinine increased significantly in the DPN and diabetic rats without peripheral neuropathy (PN) compared with control group. The treatment of DNP with gabapentin induced significant increases in ALAT and ASAT activities but LLLT treatment induced significant decreases in ALAT and ASAT activities as compared with DNP group. Neither gabapentin nor LLLT could improve the elevated levels of serum urea and creatinine in the DNP. It could be concluded that LLLT is more safe and effective than gabapentin in the management of neuropathy in diabetic rats.

Reduction of individual or combined toxicity of fumonisin B1 and zearalenone via dietary inclusion of organo-modified nano-montmorillonite in rats.

Fusarium mycotoxins are nature environmental contaminants worldwide in animal feed and human food resulting in a serious health risk. The present study aimed to evaluate the potential role of organo-modified nano-montmorillonite (OMNM) against the health risk and the oxidative stress resulted from the exposure of fumonisin (FB1) and zearalenone (ZEN) individually and in combination in rats. Eight groups of female Sprague Dawley rats were treated orally for 3 weeks including the control group, FB1 alone-treated group (50 mg/kg b.w.), ZEN alone-treated group (40 µg/kg b.w), FB1 plus ZEN-treated group, the group fed basal diet supplemented with OMNM (5 g/kg diet), and the groups fed basal diet supplemented with OMNM and treated with FB1 and/or ZEN. At the end of the experimental period, samples of blood and tissues were collected for different biochemical and histological analyses. The results revealed that administration of FB1 and/or ZEN resulted in significant disturbances in the biochemical parameters tested, lipid profiles, serum cytokines, oxidative stress indices, the activity of antioxidant enzymes, and the histological status of the liver and kidney. Co-administration of both mycotoxins indicated a synergistic effect. OMNM alone was safe and succeeded to reduce and/or prevent most of the toxicity of both mycotoxins. It could be concluded that OMNM is a novel and promising nanograde adsorbent suitable for the protection against the combined exposure to FB1 and ZEN.

Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin.

This investigation aimed to study the in vivo harmful effects of the subcutaneous injection of different methicillin resistance Staphylococcus aureus extracts (MRSA2, MRSA4, MRSA10, MRSA69, MRSA70, MRSA76, and MRSA78). Such strains represented the highest minimum inhibition concentration toward methicillin with various multidrug-resistant patterns. The obtained results revealed that rats injected with the MRSA4 extract died immediately after the last dose indicating the high cytotoxicity of MRSA4 strain (100% mortality). While the mortalities in other groups injected by the other MRSA extracts ranged from 50 to 75%. In comparison with the normal animal group, all MRSA extracts induced a hepatotoxic effect which was indicated from the significant (p < 0.01) increases in the activities of the serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) enzymes. Moreover, alkaline phosphatase (ALP) combined with a partial nephrotoxicity that was monitored from the significant elevation of serum urea concentration. While serum creatinine levels did not affect. Similarly, a significant elevation was recorded in serum levels of tumor biomarkers (alpha fetoprotein; AFP, carcinoembryonic antigen; CEA, and lactate dehydrogenase; LDH) reflecting their carcinogenic potential. On the other hand, the percentage of micronuclei (MN) in polychromatic erythrocytes from bone marrow cells was statistically significant in all groups as compared to the control group. The percentage of sperm abnormalities was statistically significant compared to the control. Different types of head abnormalities and coiled tail were recorded. Consequently, the current study focused on fighting MRSA virulence factors by the new compound ayamycin, which proved to be potent anti-virulence factor against all MRSA strains under study by significant decreasing of their streptokinase activities, hemolysin synthesis, biofilm formation, and their cell surface hydrophobicity.

Paraoxonase-1 (PON1) inhibition by tienilic acid produces hepatic injury: Antioxidant protection by fennel extract and whey protein concentrate.

This study evaluated the effect of whey protein concentrate (WPC) or fennel seed extract (FSE) on paraoxonase-1 activity (PON1) and oxidative stress in liver of tienilic acid (TA) treated rats. Six groups of rats were treated for six weeks as follows: control; WPC (0.5g/kg/day); FSE (200mg/ kg/day); TA (1g/kg/twice a week); TA (1g/kg/twice a week) plus WPC (0.5g/kg/day); TA (1g/kg/twice a week) plus FSE (200mg/kg/day). TA administration significantly increased ALT and AST besides to total- and direct bilirubin levels. Also, serum tumor necrosis factor-α and nitric oxide levels were significantly increased. Furthermore, serum PON1, and hepatic reduced glutathione, glutathione-S-transferase and Na(+)/K(+)-ATPase values were diminished matched with a significant rise in the level of hepatic lipid peroxidation. Also, triglycerides, total- and LDL-cholesterol levels were significantly elevated while HDL-cholesterol was unchanged. The administration of either WPC or FSE to TA-treated animals significantly protected the liver against the injurious effects of tienilic acid. This appeared from the improvement of hepatic functions, atherogenic markers, Na(+)/K(+) ATPase activity, endogenous antioxidants and hepatic lipid peroxidation level; where WPC showed the strongest protection effect. In conclusion, the present study indicated that WPC and FSE improve PON1 activity and attenuate liver dysfunction induced by TA. This may be attributed to the high content of antioxidant compounds in WPC and fennel extract.