Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies.
Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11–12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein (VLDL-C), white blood cells (WBCs), low-density lipoprotein cholesterol (LDL-C), and platelets (PLT) levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells (RBCs), high-density lipoprotein cholesterol (HDL-C), and hemoglobin (HB). Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure.
This experiment was established to evaluate the influence of synthetic steroid hormone and aromatase inhibitor on performance, carcass characteristics, hormonal profile and gonadal structure of broiler chickens slaughtered at two different ages. A total of 360 Cobb Avian48 chicks were sexed and distributed randomly into three groups: Tam10 group; birds received Tamoxifen10mg (Tamfen 10 mg@ ) orally at a level of 10 mg/kg body weight daily from the 3rd till the 9th day of age; BOL group: birds injected intramuscularly with Boldenone undecylenate (BOLD-GAN@ 0.1 mg/kg) at the 5th and the 9th day of age; and Control group. BOL injection or Tam supplementation improved performance traits compared with the control group. Although Tam positive effect appeared early before the 5th week of age, the BOL effect was delayed to the 6th week. BOL injection improved carcass characteristics of both sexes at both 5 and 6 weeks slaughtering ages. Regardless of treatment effect, the mortality% was higher in the late weeks of age than in the early weeks. Moreover, BOL treatment increased comb% compared with control and Tam treatments. Generally, males had significantly higher testosterone levels and lower oestrogen levels than females. Males treated with Boldenone had the highest testosterone level, although testosterone levels did not differ considerably among females of the various groups. BOL treatment females had the lowest oestrogen level. Both Tam10 and Boldenone had adverse effects on testicular and ovarian histology, affecting the typical structures. Finally, we concluded that the anabolic effect of Tam10 may be achieved in griller broilers production without changing the sex hormones assay. Although Boldenone achieved an anabolic effect without changing blood sex hormone levels, this effect is induced early with females and delayed with males, which prolongs the marketing period. The goal is to shorten this period. Therefore, this material can only be used with the possibility of separating females from males to be used with females only.
Abstract The effect of adding lactic acid bacteria (Pediococcus acidilactici) to the diet on water quality, feed utilization, growth, body composition, Hematological parameters, intestinal and liver histology of Nile tilapia, haemato-biochemical parameters, antioxidants, immunological responses, and Enzymatic Activity was investigated. Fish was distributed into Four groups; the control group (T0), T1 group (2.0 g), T2 group (2.5 g), and T3 group (3.0 g) of Pediococcus acidilactici per kg of diet. 25% of Water was changed daily and feed with 31% protein was added three times daily for 56 days. In probiotics-treated groups, growth performance, feed utilization, and fish biomass increased significantly compared to control. The biochemical and immunity parameters (Amylase, Lipase, and Protease activity) and villi height were significantly improved in probiotics groups. In conclusion, adding probiotics to fish diet improved all evaluated parameters
This research examined the role of nano curcumin (NC) on growth performances, body composition, and blood parameters of red tilapia (Oreochromis sp.) challenged with Aspergillus flavus. Fish (5.0 g ± 0.30) were randomly distributed in four equal groups (20 fish per pond in triplicates) and fed various concentrations of NC fortified with 0 (Control), 40 mg/kg (NC1), 50 mg/kg (NC2), and 60 mg/kg diet (NC3) of nano curcumin. After eight weeks of the feeding trial, the fish were challenged with A. flavus for 15 days, and the cumulative mortality was recorded. Fish fed with different concentrations of NC improved significantly (p < 0.05) the growth performances, feed utilization, and survival rate. There was no significant (p > 0.05) difference between NC2 and NC3 treatments. However, NC3 exhibited higher performances. Fish feed supplemented with NC decreased the mortality rate when challenged with A. flavus. Hence, dietary supplementation of NC enhanced the growth and health status of Oreochromis sp. and protected it from A. flavus infection. This study suggests the optimum inclusion level of NC is a 50–60 mg/kg diet.
This study investigated the effects of ultra-filtered polysaccharides from Berberis dasystachya Maxim. (UBDP) on the gut microbiota and glucose metabolism in high-fat diet/streptozotocin -induced diabetic rats, and clarified the possible action mechanisms of UBDP in the treatment of type 2 diabetes mellitus (T2DM). The results showed that UBDP administration for 4 weeks significantly ameliorated glucose tolerance, improved organ function, reduced fasting blood glucose and HbA1c levels, decreased the glycosylated hemoglobin index, improved insulin sensitivity of the pancreas, and reduced colon morphogen and oxidative stress in the diabetic rats (P < 0.05). Furthermore, the antihyperglycemic effect of 200 mg/kg UBDP was the most significant. 16S rDNA sequencing evaluated the changes in the gut microbiota of T2DM rats, and metabolites were analyzed through metabolomic profiling. Four weeks of UBDP supplementation significantly increased the relative abundance of Firmicutes and the levels of short-chain fatty acids, and the phenotypes of the gut microbiome also changed accordingly. This suggested that the gut microbiota might partially mediate the hypoglycemic effects of UBDP supplementation. Moreover, 200 mg/kg UBDP treatment significantly improved the metabolic disorder in the diabetic rats; 27 possible biomarkers were identified, mainly involved in lysine degradation; phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; bile secretion; and nicotinate and nicotinamide metabolism. To a certain extent, the levels of these biomarkers of UBDP supplementation returned to normal levels, which was related to the gut microbiota. These findings provide a theoretical foundation for the development and application of polysaccharides from Berberi dasystachya.
Magnesium, copper, zinc, iron and selenium complexes of ceftriaxone were prepared in a 1:1 ligand to metal ratio to investigate the ligational character of the antibiotic ceftriaxone drug (CFX). The complexes were found to have coordinated and hydrated water molecules, except for the Se (IV) complex, which had only hydrated water molecules. The modes of chelation were explained depending on IR, 1HNMR and UV-Vis spectroscopies. The electronic absorption spectra and the magnetic moment values indicated that Mg (II), Cu (II), Zn (II), Fe (III) and Se (VI) complexes form a six-coordinate shape with a distorted octahedral geometry. Ceftriaxone has four donation sites through nitrogen from NH2 amino, oxygen from triazine, β-lactam carbonyl and carboxylate with the molecular formulas [Mg(CFX)(H2O)2]·4H2O, [Cu(CFX)(H2O)2]·3H2O, [Fe(CFX)(H2O)(Cl)]·5H2O, [Zn(CFX)(H2O)2]·6H2O and [Se(CFX)(Cl)2]·4H2O and acts as a tetradentate ligand towards the five metal ions. The morphological surface and particle size of ceftriaxone metal complexes were determined using SEM, TEM and X-ray diffraction. The thermal behaviors of the complexes were studied by the TGA(DTG) technique. This study investigated the effect of CFX and CFX metal complexes on oxidative stress and severe tissue injury in the hepatic tissues of male rats. Fifty-six male rats were tested: the first group received normal saline (1 mg/kg), the second group received CFX orally at a dose of 180 mg/kg, and the other treated groups received other CFX metal complexes at the same dose as the CFX-treated group. For antibacterial activity, CFX/Zn complex was highly effective against Streptococcus pneumoniae, while CFX/Se was highly effective against Staphylococcus aureus and Escherichia coli. In conclusion, successive exposure to CFX elevated hepatic reactive oxygen species (ROS) levels and lipid peroxidation final marker (MDA) and decreased antioxidant enzyme levels. CFX metal complex administration prevented liver injury, mainly suppressing excessive ROS generation and enhancing antioxidant defense enzymes and in male rats.
Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins.
(1) Background: Nanocomposite films are widely applied in the pharmaceutical industry (e.g., nanodrug delivery systems-NDDS). Indeed, these nanomaterials can be produced at a large industrial scale and display valuable properties (e.g., antibacterial, renewability, biodegradability, bioavailability, safety, tissue-specific targeting, and biocompatibility), which can enhance the activity of conventional marketed drugs. (2) Aim: To fabricate and investigate the in vitro properties of the antibiotic ceftriaxone sodium (CTX) once encapsulated into sodium alginate (SA)/poly(vinyl alcohol)PVA-clay reinforced nanocomposite films. (3) Methods: Different ratios of the polymers (i.e., SA, PVA) and CTX drug were used for the synthesis of nanocomposite films by solvent casting technique. Montmorillonite (MMT), modified organically, was added as a nanofiller to increase their thermal and mechanical strength. The prepared samples were physically characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electronic microscopy (SEM), and energy-dispersive X-ray analysis (EDX). The physicochemical behavior (i.e., swelling, erosion, dissolution/drug release behavior and rat skin permeation) was also assessed. Comparisons were made with the currently marketed free CTX dosage form. (4) Results: TGA of the nanoformulation showed increased thermostability. XRD revealed its semi-crystalline nature. SEM depicted a homogeneous drug-loaded SA/PVA nanocomposite with an average size ranging between 300 and 500 nm. EDX confirmed the elemental composition and uniform distribution of mixing components. The water entrapment efficiency study showed that the highest swelling and erosion ratio is encountered with the nanoformulations S100(3) and S100D15(3). Ex vivo permeation revealed a bi-step discharge mode with an early burst liberation chased by continued drug discharge of devised nanoparticles (NPs). The dissolution studies of the drug-loaded polymer nanocomposites elicited sustained pH-dependent drug release. The cumulative drug release was the highest (90.93%) with S100D15(3). (5) Conclusion: S100D15(3) was the finest formulation. To the best of our knowledge, we also pioneered the use of solvent casting for the preparation of such nanoformulations. Polymers and reinforcing agent, concentrations and pH were rate-deterring features for the preparation of the optimized formulation. Thus, CTX-loaded SA/PVA-MMT reinforced nanocomposite appeared as a promising nanodrug delivery system (NDDS) based on its in vitro physicochemical properties.
Abstract A common and efficient analgesic-antipyretic medication for a variety of syndromes is paracetamol (PAR). The use of PAR was associated with acute kidney injury and other side effects, and its hazardous effects were influenced by oxidative stress and inflammation. Black seed oil’s primary active ingredient, thymoquinone (TQ), has anti-inflammatory, immunomodulatory, and antioxidant properties. A few animal models for drug-induced nephrotoxicity described promising outcomes of its renoprotective action. The main goal of this work was to evaluate TQ nanoparticles’ (TQNP) powerful renoprotective properties in a rat model of nephrotoxicity caused by PAR. Three groups of eight rats each were assigned; group one (the control group, CON) was given gavaged normal saline. Group 2 (PAR group, PAR) received 600 mg/kg of gavaged PAR diluted in regular saline. One hour after PAR delivery, group 3 (the TQNP group) received TQNP 0.5 mg/kg via oral administration. In rat kidney tissues, PAR resulted in renal damage, a rise in blood urea nitrogen (BUN), creatinine, cystatin C (CYC), myeloperoxidase, protein carbonyl (PC), malondialdehyde (MDA), and a decrease in nitric oxide and cellular antioxidants. In rats given PAR, TQNP effectively reduced renal damage, lowered serum levels of creatinine, BUN, and CYC, and improved oxidative stress (MDA, MYO, and PC) and inflammatory markers (TNFα and IFN-γ). TQNP treatment resulted in modestly dilated/congested blood vessels in the renal tissues of PAR. The TQNP’s renoprotective action is an effective preventative against PAR-induced nephrotoxicity, primarily by enhancing cellular defense mechanisms and reducing inflammatory and oxidative indicators in a rat model. However, additional research and clinical trials should be needed for testing in future studies.
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