Curcumin-resveratrol nano-formulation counteracting hyperammonemia in rats.

Malnutrition and low dietary protein intake could be risk factors for developing peripheral and central hyperammonemia, especially in pediatrics. Both curcumin and resveratrol proved to be effective against several hepatic and cerebral injuries. They were reported to be beneficial in lowering circulating ammonia levels, yet both are known for their low bioavailability. The use of pharmaceutical nano-formulations as delivery systems for these two nutraceuticals could solve the aforementioned problem. Hence, the present study aimed to investigate the valuable outcome of using a combination of curcumin and resveratrol in a nanoemulsion formulation, to counteract protein-deficient diet (PDD)-induced hyperammonemia and the consequent complications in male albino rats. Results revealed that using a nanoemulsion containing both curcumin and resveratrol at a dose of (5 + 5 mg/kg) effectively reduced hepatic and brain ammonia levels, serum ALT and AST levels, hepatic and brain nitric oxide levels, oxidative DNA damage as well as disrupted cellular energy performance. In addition, there was a substantial increase in brain levels of monoamines, and a decrease in glutamate content. Therefore, it can be concluded that the use of combined curcumin and resveratrol nanoemulsion is an effective means of ameliorating the hepatic and cerebral adverse effects resulting from PDD-induced hyperammonemia in rats.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Combating hematopoietic and hepatocellular abnormalities resulting from administration of cisplatin: role of liver targeted glycyrrhetinic acid nanoliposomes loaded with amino acids.

The effectiveness of cisplatin in cancer treatment renders its use vital to clinicians. However, the accompanying side effects as cachexia, emesis and liver damage necessitate the use of a dietary supplement which is capable of hindering such undesirable complications. The branched chain amino acids as well as glutamine and arginine have been proven to be effective nutritional co-adjuvant therapeutic agents. Furthermore, new pharmaceutical approaches encompass designing organ-targeted nanoformulations to increase the medicinal efficacy. Therefore, the aim of the present study was to investigate the beneficial effects of liver-targeted amino acids-loaded nanoliposomes in counteracting the adverse hematopoietic and hepatic complications associated with cisplatin. Results revealed the use of the combination of two nanoliposomal formulations (one loading leucine + isolecuine + valine, and the other loading glutamine and arginine) given orally at a dose of 200 mg/kg for twelve days was effective against cisplatin-induced toxicities represented by improvement in the complete blood picture parameters, decrease in the serum hepatic enzymes levels, amelioration of the hepatic oxidative stress and cellular energy imbalance along with reduction in the histopathological abnormalities. It can be concluded that amino acids loaded nanoliposomes could be considered a new strategy in preventing cisplatin's adverse effects.

The potential toxic effects of magnesium oxide nanoparticles and valproate on liver tissue.

The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues.

Ovarian activity and antioxidant indices during estrous cycle of Barki ewes under effect of thyme, celery and salinomycin as feed additives.

This research aimed to examine the effects of thyme, celery and salinomycin on ovarian sex hormones, reproductive traits and antioxidant status during the estrous cycle. Seventy-five mature Barki ewes aged 2-3 years with an average weight of 40 ± 1.5 kg were assigned randomly into five groups (15 head/group). Group 1 was kept as the control; groups 2 and 3 received 20 g/head/day thyme (T) and celery (C) as dried herbs, respectively. Group 4 (T×C) received 10 g thyme + 10 g celery/head/day, and group 5 was treated with salinomycin 1 g/head/day. Blood samples were collected during follicular and luteal phases of the estrous cycle. Thyme and celery and the mixture of T×C increased (P < 0.01) estradiol-17ß (E2) during the follicular phase of the estrous cycle, while only the celery group showed a marked (P < 0.001) increase in progesterone (P4) during the luteal phase compared with the control. Salinomycin supplementation decreased (P < 0.05) E2 concentrations during the follicular and luteal phases of the estrous cycle. Supplementation with thyme and celery enhanced (P < 0.001) antioxidant capacity in the luteal phase compared with the follicular stage. The salinomycin group showed increased (P < 0.01) levels of reduced glutathione (GSH) and decreased malondialdehyde (MDA) levels compared with the control group throughout luteal phase. For the interaction between estrous phases and treatments, thyme, celery, and T×C supplementation revealed an increase (P < 0.05) in superoxide dismutase (SOD), GSH, and glutathione disulfide (GSSG) levels compared with the control group during the follicular and luteal phases. Thyme and celery supplementation improved the number of services per conception and fertilization from 1st and 2nd inseminations, respectively. In conclusion, the applied treatment had significant effects on reproductive performance and antioxidant status in ewes throughout the estrous cycle.

Effect of cage density on growth rate, carcass traits, muscle amino acid profile, and antioxidant biomarkers of commercial rabbits.

The objective of this work was to elucidate the impact of cage density on growth efficiency, carcass yield, and muscle amino acid profile of fattening rabbits. In total, 96 weaned rabbits were assigned into three cage densities: low cage density (LCD) = 1425 cm2/rabbit; medium cage density (MCD) = 850 cm2/rabbit; high cage density (HCD) = 625 cm2/rabbit. Compared with the HCD, the body gain and feed conversion ratio were better in the LCD and MCD groups (P = 0.003 and 0.004, respectively). The MCD and HCD groups had lower hot carcass weight (P = 0.012) and dressing percentage (P = 0.022) than the LCD group. Compared with the HCD group, the LCD and MCD groups exhibited greater serum GSH (P = 0.029) and SOD (P = 0.032), but significantly lower levels of serum cortisol and cholesterol (P = 0.001 and 0.026, respectively). Regarding the amino acid profile of longissimus dorsi and leg muscles, the LCD group had significantly higher levels of muscle lysine and threonine than the HCD and MCD groups (P˂0.05). The current study indicates that the MCD (850 cm2/rabbit) could maintain an acceptable growth performance, carcass traits, and welfare-related parameters. Furthermore, only the low cage density (1425 cm2/rabbit) may preserve the levels of essential (lysine, isoleucine, and threonine) and nonessential (histidine, proline, and glysein) amino acids in the longissimus dorsi and leg muscles of growing rabbits.

Combined approaches for evaluation of xenoestrogen neural toxicity and thyroid dysfunction: Screening of oxido-nitrosative markers, DNA fragmentation, and biogenic amine degradation.

Anthropogenic chemicals such as parabens and triclosan are used in personal care products. Due to their ability to decrease or prevent bacterial contamination and act as preservatives, these chemicals are used in cosmetic manufacturing processes to increase the shelf life of products. In this study, we assessed the side effects of environmental estrogens (such as the xenoestrogen butylparaben and the antimicrobial agent and preservative triclosan) on thyroid function, brain monoamine levels, and DNA aberration. Forty-two male albino rats were divided into seven groups with six members each: the first group served as control; the second and the third groups were treated with butylparaben 10 and 50 mg/kg body weight, respectively; the fourth and fifth groups were treated with triclosan 10 and 50 mg/kg body weight, respectively; and the sixth and seventh groups were treated with butylparaben plus triclosan 10 and 50 mg/kg body weight, respectively. After 60 days, blood samples were collected and brain specimens were divided into striatum, midbrain, cortex, and thalamus. Thyroid function and levels of monoamines and monoamine metabolites were determined for each brain area. Comet assay was used for brain tissue analysis. The results showed that butylparaben and triclosan and their combinations induced hypothyroidism and disrupted monoamine levels, leading to a decrease in catecholamine and serotonin levels, and accelerated production of 5-hydroxyindoleacetic acid. The obtained data indicate that anthropogenic chemicals such as butylparaben and triclosan have harmful effects on thyroid and brain function and accelerate cell destruction and mutation, as evidenced by single-stranded DNA breaks in the comet assay.

Impact of dietary zinc oxide nanoparticles on selected serum biomarkers, lipid peroxidation and tissue gene expression of antioxidant enzymes and cytokines in Japanese quail.

BACKGROUND: The use of zinc oxide in the form of nanoparticles (ZnO-NPs) is of great benefit due to its potent effectiveness and higher bioavailability compared to zinc oxide. This study aimed to investigate the impact of dietary inclusion of different doses of ZnO-NPs on selected serum biomarkers, lipid peroxidation and tissue gene expression of antioxidant enzymes and cytokines in Japanese quail. Eighty Japanese quails (Coturnix japonica) (45 days old) were randomly divided into four groups (20 birds for each) with 4 replicates (5 birds each). Birds in the first group were fed a basal diet alone and served as a control (C). Birds in groups 2-4 were fed the basal diet supplemented with ZnO-NPs at doses of 15 mg/kg, 30 mg/kg and 60 mg/kg for a period of 60 days. At the end of the experiment, all birds were sacrificed to collect blood in a plain vacutainer, whereas liver and brain tissues were stored frozen at -80 °C. The obtained sera were used for the analysis of selected biochemical parameters, whereas tissue homogenates were used for the estimation of zinc, oxidative stress biomarkers and gene expression of selected antioxidant enzymes and cytokines. RESULTS: ZnO-NPs (30 and 60 mg/kg) induced a significant decrease in serum triacylglycerol (TAG) compared to the control. ZnO-NPs did not affect the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin and tissue zinc concentrations but reduced the malondialdehyde (MDA) levels compared to the control. The liver retained a higher zinc concentration than that of brain tissue. In a dose-dependent manner, ZnO-NPs upregulated the mRNA levels of antioxidant enzymes (superoxide dismutase: SOD1; catalase: CAT; glutathione peroxidase-1: GPX 1) and pro-inflammatory cytokines (interferon α: IFN-α; interleukin 6: IL-6) in liver and brain tissues. CONCLUSION: The current study suggests the inclusion of ZnO-NPs, particularly 60 mg/kg, in the diet of Japanese quails to improve antioxidant and immune status.

Melatonin regulates neurodegenerative complications associated with NAFLD via enhanced neurotransmission and cellular integrity: a correlational study.

Nonalcoholic fatty liver disease (NAFLD) is recognized globally as the leading cause of chronic liver diseases whose patients are asymptomatic and are diagnosed incidentally. It increases the rate of mortality which is usually related to cardiovascular events; however, scarce attention has been addressed to brain damage. This study was designed to investigate the impact of melatonin (MEL; 10 mg/kg) on overcoming the hepato and neuro-complications associated with high fat, high fructose (HFHF) diet induced-NAFLD in rats. NAFLD was induced by HFHF diet for 8 consecutive weeks. MEL was given orally for the last 10 days. Rats' general behavior was assessed by; open field test (OFT) and forced swimming test (FST). On biochemical level; serum levels of glucose, insulin, alanine transaminase and aspartate transaminase as well as the hepatic levels of triglycerides and total cholesterol were evaluated. Monoamines' brain levels, their metabolites in addition to the brain level of 8-hydroxyguanosine (8-OHdG) were evaluated. Moreover, the levels of tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NOx) were measured in both the liver and brain tissues. Oral treatment of NAFLD induced rats with MEL for ten consecutive days managed to increase the activity of the rats in the OFT and decrease the immobility period in the FST. Moreover, MEL reduced monoamines turnover and elevated brain 8-OHdG level. It also had the ability to counteract the elevated levels of GSH, NOx, MDA, and TNF- α in liver and brain tissues. MEL can be suggested to be a promising candidate for treating the neuronal side effects related to NAFLD.

Nicotinamide extrudates as novel anti-aging and collagen promoting platform: a comparative cosmeceutical study versus the gel form.

The objective of the study was to explore the potential of a novel nicotinamide extrudate as an anti-aging platform compared to the conventional gel. Nicotinamide extrudates were prepared by hot melt extrusion and characterized pharmaceutically for their thermal behavior, mositure uptake, skin adhesion, and deposition in different skin layers. The pharmacological potential of the extrudates was explored in terms of induction of skin amino acids, cellular energy estimation, 8-hydroxy-2-deoxyguanosine content, Nitrate + nitrite content and histological chacaterization of collagen area percent. Results revealed that the extrusion technique managed to amorphize nicotinamide and enhance its skin deposition (46%) compared to the gel form which only showed about 10% deposition, owing to the mucoadhesive nature of the former. Extrudates were also found superior to the gel form as demonstrated by the increased amino acids level (glycine, proline, hydroxyproline), increased cellular energy, decreased oxidative stress and increased collagen formation. Nictotinamide extrudates were proven to be a scalable promising anti-aging platform which are worthy of entering the cosmeceutical market as products.

Antioxidant activity and phycoremediation ability of four cyanobacterial isolates obtained from a stressed aquatic system.

Cyanobacteria are natural enormous sources of various biologically active compounds with great contributions in different industries. This study aimed to explore and characterize novel cyanobacterial isolates with antioxidant activity and potent phycoremediation ability from Egyptian wastewater canals. The in vitro biological activity of these isolates and their potential ability to take up nutrients and heavy metals from wastewater were examined. The obtained isolates were sequenced and deposited in database under accession numbers, KY250420.1, KY321359.1, KY296359.1 and KU373076.1 for Nostoc calcicola, Leptolyngbya sp., Nostoc sp., and Nostoc sp., respectively. Leptolyngbya sp. (KY321359.1) showed the lowest identity (90%) with the nearest deposited sequence in database. While the isolate Nostoc sp. (KU373076.1) showed the highest total phenolic content as well as the highest levels of caffeic, ferulic and gallic acids. Consequently, it presented the highest antioxidant scavenging activity. All studied isolates revealed potent ability in chelating nutrients and removing heavy metals from wastewater. In conclusion, this study provides a taxonomic, biochemical and molecular evidence of four novel cyanobacterial isolates with antioxidant activity and potential phycoremediation ability.

Effects of dietary curcumin and acetylsalicylic acid supplements on performance, muscle amino acid and fatty acid profiles, antioxidant biomarkers and blood chemistry of heat-stressed broiler chickens.

The objective was to investigate the effects of dietary curcumin and acetylsalicylic acid (ASA) on the performance and physiological responses of broiler chickens under chronic thermal stress. One hundred and sixty day-old male chicks (Ross 308) were divided equally into 4 groups (each contained 4 replicates). On the day 22 of age and thereafter, the first group (TN) was raised in a thermoneutral condition (23 ±â€¯1 °C), while the second group (HS) was subjected to 8 h of thermal stress (34 °C) and both groups fed the basal diet with no supplements. The third (CR) and fourth (AS) groups were subjected to the same thermal stress conditions and fed curcumin-supplemented diet (100 mg curcumin kg-1 diet) and ASA-supplemented diet (1 g ASA kg-1 diet), respectively. Dietary treatment had a significant effect on ADFI (P = 0.041), average daily gain (P = 0.013) and final body weight (P = 0.001). The curcumin-supplemented had higher values for these measures compared with other experimental groups (P < 0.05). Also, the dietary curcumin supplement significantly increased the carcass yield as compared to the HS group (P < 0.05). Compared with the HS group, the dietary curcumin and ASA supplements decreased the concentration of malondialdehyde in the breast muscles (P = 0.014). Both dietary supplements exhibited a marked ability to restore the serum TAC, Na and K in heat-stressed broiler chickens. The current study reported a remarkable ability of curcumin supplement to restore the concentrations of polyunsaturated fatty acids (PUFA) in the breast muscles of heat-stressed broilers, including α-linolinec acid and Docosahexaenoic acid (P = 0.009 and 0.001, respectively). It could be concluded that supplemental dietary curcumin or ASA enhanced growth performance and antioxidant biomarkers of heat-stressed broilers. Moreover, curcumin might be an effective dietary supplement to alleviate the adverse effect of chronic thermal stress on carcass yield and meat quality.

Carcass yields, muscle amino acid and fatty acid profiles, and antioxidant indices of broilers supplemented with synbiotic and/or organic acids.

The objective of the current research was to explore the possible impacts of dietary supplementation with synbiotic and/or organic acids (OA) on the performance traits, carcass yields and muscle amino acid and fatty acid (FA) profiles of broilers. Randomly, a total of 160 day-old chicks (Ross 308) were assigned into four equal groups (40 birds each), with each group subdivided into eight replicates (five birds/pen). The control group (CON) fed the basal diet with no supplements, while diets of the treated groups were supplemented with OA (Sodium butyrate 40%; 1 g/kg), synbiotic (comprised Bacillus subtilis, Saccharomyces cerivisiae, Streptococcus faecium, Mannan-Oligosaccharides and ß-Glucan; 1 g/kg) and equal mix of OA and synbiotic (2 g/kg). Broilers fed the diets supplemented with synbiotic or synbiotic plus OA produced a significantly higher feed utilization efficiency (p = 0.021) and carcass yields (p = 0.038) than the CON and OA-supplemented groups. The group fed the diet supplemented with the synbiotic showed lowered serum cholesterol (p = 0.049), triglycerides (p = 0.001) and very low density lipoprotein (p = 0.032) when compared with the CON group. Regarding the polyunsaturated FA (PUFA) of breast muscles, synbiotic-supplemented birds had significantly lower n-6:n-3 ratio (p = 0.047), however, a greater hypocholesterolaemic to hypercholesterolaemic FA (H/H) ratio was reported when compared with the CON group (p = 0.002). Among the essential amino acids, the contents of leucine and methionine in the breast (p = 0.032 and 0.007 respectively) and thigh (p = 0.023 and 0.003 respectively) muscles were greater in the synbiotic-supplemented birds compared with the CON group. In conclusion, the synbiotic-supplemented diet improved the PUFA:SFA, n-6:n-3 and H/H ratios by altering the FA composition of broiler muscles, which are important with regards to human health.

Hydrogen peroxide modulates redox status, energy metabolism, and gene expression in a dose- and time-dependent manner in rat liver.

AIM: The aim of this study was to investigate the effect of three different hydrogen peroxide (H2 O2 ) levels on blood and liver oxidative status, energy metabolites, and gene expression in male albino rats at two time intervals (2 and 4 weeks). METHODS: A total of 32 rats were divided into four groups. The first group received tap water and served as control. The second group received low dose of hydrogen peroxide (H2 O2 ; 0.25%), The third group received medium dose of H2 O2 (0.5%) and the fourth group received high dose of H2 O2 (1%) in drinking water. RESULTS: Present data showed that medium and high dose increased oxidative stress markers, decreased cell energy, and decreased antioxidant enzyme gene expression (GPx and Nrf2) and its downstream in contrast low dose did not show significant effects. CONCLUSION: This study might indicate that hydrogen peroxide medium level is the best dose for redox model status.

Amisulpride-CD-Loaded Liposomes: Optimization and In Vivo Evaluation.

Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of schizophrenia. The effect of different variables, i.e., the type of cyclodextrins (CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes (single and double loaded) was studied by applying 23 full factorial design. Double-loaded liposomes are loaded with AMS-hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) in the aqueous phase and free drug in the lipophilic bilayer, while single-loaded liposomes are loaded only with AMS-HP-ß-CD in the aqueous phase. Entrapment efficiency, particle size, polydespersibility, and zeta potential were selected as dependent variables. Design Expert® software was used to obtain an optimized formulation with high entrapment efficiency (64.55 ± 1.27%), average particle size of 40.1 ± 2.77 nm, polydespersibility of 0.44 ± 0.37, and zeta potential of - 48.8 ± 0.28. Optimized formula was evaluated for in vitro release, surface morphology and stability study was also conducted. AMS-HP-ß-CD in double-loaded liposomes exhibited higher drug release than those in the conventional liposomes and in the single-loaded liposomes. The maximum plasma concentration (Cmax) of AMS in optimized AMS-HP-ß-CD double-loaded liposomal formulation increased by 1.55- and 1.29-fold, as compared to the commercial tablets and conventional liposomes, respectively. However, the relative bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of commercial tablet and conventional liposomes, respectively.

Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

BACKGROUND: Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. METHODS: Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2ndgroup; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. RESULTS: PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological alterations and the overall results of the nano-emulsion (5 mg/kg) were comparable to curcumin (50 mg/kg). CONCLUSIONS: The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.

The neuroprotective effect of mesenchymal stem cells on an experimentally induced model for multiple sclerosis in mice.

Multiple sclerosis (MS) is a chronic autoimmune demyelinating neurodegenerative central nervous system disorder. The aim of the present study was to investigate the prophylactic effect exerted by the one-time intraperitoneal injection of mesenchymal stem cells (MSCs) 1 × 106 and 14-day intraperitoneal injection of methylprednisolone (MP) 40 mg/kg in an experimental autoimmune encephalomyelitis (EAE). EAE was induced by intradermal injection of rat spinal cord homogenate with complete Freund's adjuvant in Swiss mice. Results of MSCs and MP-treated mice showed a significantly milder disease and fewer clinical scores compared to control mice. They suppressed tumor necrosis factor-alpha and myeloperoxidase and increased interleukin 10, whereas thiobarbituric acid reactive substances and nitric oxide brain contents were reduced to comparable levels between treatment groups. Brain content of GSH was significantly higher in MSCs-treated mice than control mice. It is evident that MSCs have relevant prophylactic effect in an animal model of MS and might represent a valuable tool for stem cell based therapy in MS.

Eugenol alleviates acrylamide-induced rat testicular toxicity by modulating AMPK/p-AKT/mTOR signaling pathway and blood-testis barrier remodeling.

This study aimed to investigate the effects of eugenol treatment on reproductive parameters in acrylamide (ACR)-intoxicated rats. The study evaluated alterations in relative testes and epididymides weights, sperm quality, serum hormonal status, seminal plasma amino acids, testicular cell energy and phospholipids content, oxidative and nitrosative stress parameters, adenosine monophosphate-activated protein kinase/ phosphoinositide 3-kinase/phosphor-protein kinase B/mammalian target of rapamycin (AMPK/PI3K/p-AKT/mTOR) signaling pathway, blood-testis barrier (BTB) remodeling markers, testicular autophagy and apoptotic markers, as well as histopathological alterations in testicular tissues. The results revealed that eugenol treatment demonstrated a significant improvement in sperm quality parameters, with increased sperm cell concentration, progressive motility live sperm, and a reduction in abnormal sperm, compared to the ACR-intoxicated group. Furthermore, eugenol administration increased the levels of seminal plasma amino acids in a dose-dependent manner. In addition, eugenol treatment dose-dependently improved testicular oxidative/nitrosative stress biomarkers by increasing oxidized and reduced glutathione levels and reducing malondialdehyde and nitric oxide contents as compared to ACRgroup. However, eugenol treatment at a high dose restored the expression of AMPK, PI3K, and mTOR genes, to levels comparable to the control group, while significantly increasing p-AKT content compared to the ACRgroup. In conclusion, the obtained findings suggest the potential of eugenol as a therapeutic agent in mitigating ACR-induced detrimental effects on the male reproductive system via amelioration of ROS-mediated autophagy, apoptosis, AMPK/p-AKT/mTOR signaling pathways and BTB remodeling.

Neurological study on the effect of CeNPs and/or La Cl3 on adult male albino rats.

Lanthanides are a group of 15 elements (8 heavy and 7 light) grouped for their proximity in the chemical and physical properties. Recently, this group of elements has received great attention because of their importance, and their entrance into many industrial technologies making the probability of the living organisms' exposure to it increase. The present study aims to study ability of cerium nanoparticles (CeNPs) or lanthanum (LaCl3) to cross the blood brain barrier also, investigate their neuro effect separately or together on some parameters in six brain areas (cortex, cerebellum, hippocampus, striatum, midbrain, and hypothalamus) of the adult male albino rats. The results showed the ability of both elements to distribute and accumulate in the different brain areas. Also, the results of CeNPs or LaCl3 treatment were in the same line where each element caused a significant decrease in norepinephrine (NE), dopamine (DA), serotonin (5-HT) and GABA accompanied with a significant increase in 5- hydroxyl indoleacetic acid (5-HIAA) glucose level. On the other hand, GSH and MDA showed a significant decrease after CeNPs treatment while, with LaCl3 treatment, MDA showed a significant increase in the different brain areas after 3 weeks of treatment. The coadministration of CeNPs and La Cl3 caused an ameliorating effect in all the tested parameters. In conclusion, from the previous studies the effects of lanthanides in the present study may be in part due to its effect on the release or turnover of neurotransmitters and insulin secretion. Finally, the ameliorative effect of CeNPs may be regarded as its high activity to scavenge the free radicals.

Anti-depressant effect of Naringenin-loaded hybridized nanoparticles in diabetic rats via PPARγ/NLRP3 pathway.

Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles (NAR-HNPs) and NAR on depression induced by streptozotocin (STZ) in rats. NAR-HNPs formula with the highest in vitro NAR released profile, lowest polydispersity index value (0.21 ± 0.02), highest entrapment efficiency (98.7 ± 2.01%), as well as an acceptable particle size and zeta potential of 415.2 ± 9.54 nm and 52.8 ± 1.04 mV, respectively, was considered the optimum formulation. It was characterized by differential scanning calorimetry, examined using a transmission electron microscope, and a stability study was conducted at different temperatures to monitor its stability efficiency showing that NAR-HNP formulation maintains stability at 4 °C. The selected formulation was subjected to an acute toxicological test, a pharmacokinetic analysis, and a Diabetes mellitus (DM) experimental model. STZ (50 mg/kg) given as a single i.p. rendered rats diabetic. Diabetic rat groups were allocated into 4 groups: one group received no treatment, while the remaining three received oral doses of unloaded HNPs, NAR (50 mg/kg), NAR-HNPs (50 mg/kg) and NAR (50 mg/kg) + peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662 (1mg/kg, i.p.) for three weeks. Additional four non-diabetic rat groups received: distilled water (normal), free NAR, and NAR-HNPs, respectively for three weeks. NAR and NAR-HNPs reduced immobility time in forced swimming test and serum blood glucose while increasing serum insulin level. They also reduced cortical and hippocampal 5-hydroxyindoeacetic acid, 3,4-Dihydroxy-phenylacetic acid, malondialdehyde, NLR family pyrin domain containing-3 (NLRP3) and interleukin-1beta content while raised serotonin, nor-epinephrine, dopamine and glutathione level. PPAR-γ gene expression was elevated too. So, NAR and NAR-HNPs reduced DM-induced depression by influencing brain neurotransmitters and exhibiting anti-oxidant and anti-inflammatory effects through the activation PPAR-γ/ NLRP3 pathway. NAR-HNPs showed the best pharmacokinetic and therapeutic results.