Electrospun Tamarindus indica-loaded antimicrobial PMMA/cellulose acetate/PEO nanofibrous scaffolds for accelerated wound healing: In-vitro and in-vivo assessments.

In this work, Tamarindus indica (T. indica)-loaded crosslinked poly(methyl methacrylate) (PMMA)/cellulose acetate (CA)/poly(ethylene oxide) (PEO) electrospun nanofibers were designed and fabricated for wound healing applications. T. indica is a plant extract that possesses antidiabetic, antimicrobial, antioxidant, antimalarial and wound healing properties. T. indica leaves extract of different concentrations were blended with a tuned composition of a matrix comprised of PMMA (10 %), CA (2 %) and PEO (1.5 %), and were electrospun to form smooth, dense and continuous nanofibers as illustrated by SEM investigation. In vitro evaluation of T. indica-loaded nanofibers on normal human skin fibroblasts (HBF4) revealed a high compatibility and low cytotoxicity. T. indica-loaded nanofibers significantly increased the healing activity of scratched HBF4 cells, as compared to the free plant extract, and the healing activity was significantly enhanced upon increasing the plant extract concentration. Moreover, T. indica-loaded nanofibers demonstrated significant antimicrobial activity in vitro against the tested microbes. In vivo, nanofibers resulted in a superior wound healing efficiency compared to the control untreated animals. Hence, engineered nanofibers loaded with potent phytochemicals could be exploited as an effective biocompatible and eco-friendly antimicrobial biomaterials and wound healing composites.

Formulation and evaluation of simvastatin cubosomal nanoparticles for assessing its wound healing effect.

Wound healing is one of the most challenging medical circumstances for patients. Pathogens can infect wounds, resulting in tissue damage, inflammation, and disruption of the healing process. Simvastatin was investigated recently, as a wound healing agent that may supersede the present therapies for wounds. Our goal in this paper is to focus on formulation of simvastatin cubosomes for topical delivery, as a potential approach to improve simvastatin skin permeation. By this technique its wound healing effect could be improved. Cubosomes were prepared using the top-down method and the prepared cubosomes were characterized by several techniques. The most optimal simvastatin cubosomal formulation was then included in a cubogel dosage form using different gelling agents. The results showed that the average particle size of the prepared cubosomes was 113.90 ± 0.58 nm, the entrapment efficiency was 93.95 ± 0.49% and a sustained simvastatin release was achieved. The optimized formula of simvastatin cubogel displayed pseudoplastic rheological behavior. This same formula achieved enhancement in drug permeation through excised rat skin compared to free simvastatin hydrogel with flux values of 46.18 ± 2.12 mcg cm-2 h-1 and 25.92 ± 3.45 mcg cm-2 h-1 respectively. Based on the in-vivo rat studies results, this study proved a promising potential of simvastatin cubosomes as wound healing remedy.

Development and in vivo evaluation of therapeutic phytosomes for alleviation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with progressive articular damage, functional loss and comorbidity. Conventional RA therapy requires frequent dosing and prolonged use, and usually results in poor efficacy and severe toxicity. In the current study, for the first time, we describe a combination strategy using phytosomes co-loaded with curcumin (CUR) and leflunomide (LEF) to improve the clinical outcomes of RA therapy. Exploiting 23 factorial design, various compositions of CUR and LEF co-loaded phytosomes (CUR/LEF-phytosomes) were successfully prepared and were extensively characterized (e.g., particle size, zeta potential, drugs encapsulation efficiency, morphology, DSC, FTIR and release kinetics). The optimal CUR/LEF-loaded phytosomes (F2) demonstrated high stability and spherical morphology with a particle size of ca. 760 nm and negative zeta potential value of - 55.7, high entrapment for both drugs, and sustained release profile of the entrapped medications. In vivo, oral administration of the CUR/LEF-phytosomes (F2) in arthritic rats resulted in significant reduction of paw swelling and inflammatory markers, compared to the free drugs and their physical mixture. Histopathological examination revealed significant improvement in phytosomes-treated animal group with no signs of arthritis. CUR/LEF-loaded phytosomes provide an auspicious strategy for alleviation of RA.

Gum Arabic nanoformulation rescues neuronal lesions in bromobenzene-challenged rats by its antioxidant, anti-apoptotic and cytoprotective potentials.

Bromobenzene (BB) is a hazardous environmental contaminant because of its multiple routes of exposure and the toxicity of its bio-derivates. It could elicit neuronal alterations by stimulating redox imbalance and apoptotic pathways. Gum Arabic (GA) protected the hippocampus of a type 2 diabetic rat model from cognitive decline. Whether gum Arabic nanoemulsion (GANE) can increase the neuroprotectant potency of GA in fighting BB-associated neurological lesions is the question to be answered. To accomplish this objective, 25 adult male Wistar rats were randomly and equally assigned into five groups. Control received olive oil (vehicle of BB). BB group received BB at a dose of 460 mg/kg BW. Blank nanoemulsion (BNE) group supplemented with BNE at 2 mL of 10% w/v aqueous suspension/kg BW. GANE group received GANE at a dose of 2 mL of 10% w/v aqueous suspension/kg BW. BB + GANE group exposed to BB in concomitant with GANE at the same previous doses. All interventions were carried out daily by oral gavage for ten consecutive days. BB caused a marked increase in malondialdehyde and succinate dehydrogenase together with a marked decrease in reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and lactate dehydrogenase in the brain. BB was accompanied by pathological deteriorations, amyloidosis, and reduced immuno-expression of integrase interactor 1 in the hippocampal region. Administration of GANE was beneficial in reversing the aforementioned abnormalities. These results pave the road for further discovery of nano-formulated natural products to counter the threats of BB.

Ameliorative effects of thymoquinone on titanium dioxide nanoparticles induced acute toxicity in rats.

Although the nanoparticles had a beneficial activity, it had also adverse effects as a result of generation of oxidative stress. The current study aimed to assess the ameliorative effect of thymoquinone (TQ) on titanium dioxide nanoparticles (TiO2 NPs) induced acute toxicity in male rats. Forty-eight male rats were distributed into four equal groups (12 rats each). Group (1) received single oral dose of TiO2 NPs (300 mg/kg), Group (2) received TiO2 NPs and TQ (20 mg/kg), Group (3) received TQ and group (4) received only the vehicle and served as control group. TiO2 NPs intoxicated group showed increased the level of lipid peroxidation product (LPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased the level of antioxidants and testosterone. Vascular and degenerative changes in the liver and testes were observed by light microscopy as well as presence of TiO2 NPs in the lysosomes by electron microscopy. Treatment with TQ revealed improvement of the biochemical parameters, histology and ultrastructure of the liver and testes. It was concluded that acute intoxication of rats with TiO2 NPs induced adverse effect in the liver and testes. Administration of TQ has an ameliorative effect against oxidative stress induced by TiO2 NPs intoxication.

Corrigendum to "Protective Effect of Ginkgo biloba and Magnetized Water on Nephropathy in Induced Type 2 Diabetes in Rat".

[This corrects the article DOI: 10.1155/2018/1785614.].

Protective Effect of Ginkgo biloba and Magnetized Water on Nephropathy in Induced Type 2 Diabetes in Rat.

We aimed in our current study to explore the protective effect of Ginkgo biloba (GB) and magnetized water (MW) against nephrotoxicity associating induced type 2 diabetes mellitus in rat. Here, we induced diabetes by feeding our lab rats on a high fat-containing diet (4 weeks) and after that injecting them with streptozotocin (STZ). We randomly divided forty rats into four different groups: nontreated control (Ctrl), nontreated diabetic (Diabetic), Diabetic+GB (4-week treatment), and Diabetic+MW (4-week treatment). After the experiment was finished, serum and kidney tissue samples were gathered. Blood levels of glucose, triglycerides, cholesterol, creatinine, and urea were markedly elevated in the diabetic group than in the control group. In all animals treated with GB and MW, the levels of urea, creatinine, and glucose were significantly reduced (all P < 0.01). GB and MW attenuated glomerular and tubular injury as well as the histological score. Furthermore, they normalized the contents of glutathione reductase and SOD2. In summary, our data showed that GB and MW treatment protected type 2 diabetic rat kidneys from nephrotoxic damages by reducing the hyperlipidemia, uremia, oxidative stress, and renal dysfunction.

Dual-responsive lidocaine in situ gel reduces pain of intrauterine device insertion.

The most effective and safe contraceptive method, intrauterine devices (IUDs), is still underutilized due to the pain barrier during IUD insertion. Lidocaine, a well-known local anesthetic, can be used to relieve IUD insertion pain. This study aimed at formulation, in vitro, in vivo and clinical evaluation of a novel lidocaine dual-responsive in situ gel. Pluronic and Gelrite® were used as thermosenstive and ion-activated polymers, respectively. In situ gels containing 2% lidocaine, pluronics and/or Gelrite® were prepared. The optimized dual-responsive formula (F5) was clear, with 95% drug content, free flowing at room temperature and gel at vaginal temperature (Tgel of 28 °C). This optimized dual-responsive in situ gel was found to be superior to single-responsive one due to presence of Gelrite®, imparting resistance to dilution effect of simulated vaginal fluids. DSC thermograms revealed no interaction between formulation components. Biocompatibility study showed no degeneration, necrosis or inflammation. Optimized dual-responsive in situ gel was further evaluated for pain reduction efficiency via a pilot randomized, double-blinded, placebo-controlled clinical trial showing ease of self-administeration by patients and significant pain reduction induced at all steps of IUD insertion. In conclusion, lidocaine dual-responsive in situ gel can be effectively used in prevention of pain during IUD insertion.

Protective effects of thymoquinone and avenanthramides on titanium dioxide nanoparticles induced toxicity in Sprague-Dawley rats.

The protective effect of thymoquinone (TQ), the major active ingredient of Nigella sativa seeds, and avenanthramides (AVA) enriched extract of oats on titanium dioxide naonparticles (TiO2 NPs) induced toxicity and oxidative stress in Sprague-Dawley (SD) rats was investigated. Sixty rats were divided into 6 equal groups. The first, second, third, fourth and fifth groups received TiO2 NPs, TiO2 NPs and TQ, TiO2 NPs and AVA, TQ only, or AVA only for 6 weeks. The sixth group served as the control. Exposure to TiO2 NPs resulted in increased liver enzyme markers, oxidative stress indices, tumor necrosis factor alpha (TNF-α) and DNA damage. Histopathological alterations were also observed in the liver, brain, lung, kidney, heart and testes. Co-administration of TQ and AVA with TiO2 NPs decreased the level of liver enzymes, oxidative stress, TNF-α and DNA damage. Furthermore, TQ and AVA increased the total antioxidant and glutathione (GSH) levels. In conclusion, TiO2 NPs induce hazardous effects in different organs and are closely related to oxidative stress. TQ and AVA have antioxidative and anti-inflammatory effect against the detrimental effect of TiO2 NPs.

Phimosis in male dromedary camels: Clinical findings and changes in the hemogram, nitric oxide metabolites, and testosterone concentrations.

The objectives of this study were to elucidate the clinical findings in male dromedary camels with phimosis (PHI, n = 43) and to investigate the association of this syndrome with the hemogram, nitric oxide metabolites (NOMs), and testosterone concentrations. History and signalment were obtained, and a breeding soundness examination was performed. The penis was exteriorized after administration of a pudendal nerve block. Abnormal masses obtained from the prepuce and penis were prepared for histopathology. Blood samples for hemogram assessment were taken from the diseased animals and from 10 healthy control males. Total nitrates/nitrites were determined in sera using the Griess assay. Testosterone was estimated in sera using ELISA. Phimosis associated with detectable pathologic lesions, mainly including ulcerative posthitis and lacerated glans penis, was present in 34 (79.1%) of the 43 cases (PHI-P), whereas the remaining nine (20.9%) of the 43 cases had no noticeable lesions (PHI-N). The PHI-P group showed higher leukocyte counts (P = 0.001), especially neutrophils (P = 0.0001), and greater NOM concentrations (P = 0.002) than the PHI-N and control groups. However, testosterone concentrations did not differ among groups. In conclusion, PHI in the male dromedary camels was mainly associated with ulcerative posthitis and laceration of the glans penis. The presence of pathologic lesions in cases with PHI was associated with leukocytosis, neutrophilia, and high NOM concentrations.

Role of vitamin C and selenium in attenuation of nicotine induced oxidative stress, P53 and Bcl2 expression in adult rat spleen.

UNLABELLED: Forty adult female rats were randomly divided into four groups: control, nicotine, nicotine+vitamin C and nicotine+selenium group. Splenic tissues concentrations of thiobarbituric acid reactive substances (TBARS), nitric oxide, superoxide dismutase (SOD) and catalase (CAT) activities were measured. The P53 and Bcl2 proteins were detected by Western blot and their expression in splenic tissues were measured by quantitative real time PCR in all groups. Compared to control group, nicotine increased the concentrations of TBARS and nitric oxide significantly. However, Vit. C or Se supplementation with nicotine caused a significant decrease in these concentrations. SOD and CAT activities of nicotine group decreased significantly compared to control group. Treatment with Vit. C or Se plays a significant role in elevation of SOD and CAT activities. In splenic tissues, nicotine significantly decreases the protein levels and the mRNA expression of P53 and increases the protein levels of Bcl2 and its expression. Administration of Vit. C. to nicotine-treated rats completely reversed the decrease in P53 levels and its mRNA expression and the increase in Bcl2 levels and its mRNA expression to the control values. In contrast, Se administration did not induce any significant changes in these genes levels or expressions compared to nicotine group. CONCLUSION: Vit. C supplementation to nicotine treated rats was more effective than selenium in attenuation of nicotine-induced oxidative stress, p53 and Bcl2 expression in rat spleen tissues.

Protective effects of thymoquinone and l-cysteine on cadmium-induced reproductive toxicity in rats.

This study was conducted to investigate the possible protective role of thymoquinone (TQ) and l-cysteine on the reproductive toxicity of male rats induced by cadmium chloride (CdCl2). Forty rats were divided into four even groups. The first group served as untreated control. The second, third and fourth groups received CdCl2, CdCl2 and TQ, and CdCl2 and l-cysteine, respectively for 56 days. Cd exposure caused spermatological damage (decrease sperm count and motility and increased the rates of sperm abnormalities), decrease serum testosterone level and increased oxidative stress. Histological alterations were also observed in the form of vascular and cellular changes in CdCl2 treated rats. The vascular changes were congestion of the blood vessels with interstitial edema in the testes, epididymis, seminal vesicle and prostate. The cellular changes were in the form of degenerative changes with presence of multinucleated giant cells in the lumen of seminiferous tubules, vacuolation and sloughing of the lining epithelium of the epididymis, seminal vesiculitis and prostatitis. Co-administration of TQ and l-cysteine with CdCl2 increased glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and testosterone and reduced lipid peroxidation (LPO) activity. In conclusion, our results showed that TQ and l-cysteine can ameliorate the deleterious effects of CdCl2 probably by activating testicular endocrine and antioxidant systems.

Effects of estrogen on hyperglycemia and liver dysfunction in diabetic male rats.

OBJECTIVE: To study the possible beneficial effect of estrogen (17ß-estradiol E(2)) on hyperglycemia, oxidative stress and liver dysfunctions in STZ-induced diabetic rats. A total of 40 albino male rats were randomly divided into four groups: a control group (I), a diabetic group (II), a group given 17ß estradiol (E(2)) for 15 days (III), and a diabetic group given E(2) for 30 days (IV). Diabetes was induced in the rats by 65 mg/kg streptozosin (STZ) via an intraperitoneal (i.p.) injection. E(2) was given in a dose of 500ug/kg/day by oral gavage. RESULTS: E(2) administration significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance of groups III and IV. In addition, E(2) enhanced glutathione peroxidase (GPX) and reduced lipid peroxidation in the hepatic tissues (as compared to diabetic rats). E(2) caused significant decrease of plasmatic phosphatase alkaline (PAL), lactate dehydrogenase (LDH), aspartate and lactate transaminases (AST and ALT) activities of group III and IV compared to group II. Moreover, E(2) restored the histological structure of the liver and pancreas of treated groups and increased the insulin receptors expression in the liver of groups III and IV compared to diabetic rats. Notably, these beneficial effects of E(2) on diabetic rats were more prominent in group IV compared to those of group III. CONCLUSION: E(2) has a beneficial effect on hyperglycemia, oxidative stress and ameliorates the liver dysfunction in diabetic rats and these effects may be mediated through stimulating ß-cell proliferation in pancreas and increased the insulin receptor expression in the liver tissues.