Comprehensive Analysis of Curcumin Zinc Oxide Nanoparticles, Synthesis, Characterization, and Cytogenotoxic Profiling.

Curcumin from turmeric (Curcuma longa) has traditionally been used due to its pharmacological properties, such as anticancer, anti-inflammatory, cholesterol-lowering, and antioxidant activities, but has had limitations in use due to low bioavailability. Nanoparticles have protuberant efficacies to diagnose or cure a variety of diseases, including tumors, by fine-tuning their size, structure, and physicochemical characteristics. This study aims to develop a new dosage form of curcumin nanoparticles with zinc oxide to enhance its therapeutic efficacy against cancer and cause no damage to genetics. Curcumin zinc oxide nanoparticles were prepared and characterized by using a Zeta sizer, ultraviolet (UV)-spectrophotometer, scanning electron microscope (SEM), and Fourier transform infrared (FTIR) spectroscopy. Different concentrations range from 40 to 0.078 µg/mL, and these nanoparticles were evaluated for their anticancer activity by colorimetric analysis (MTT assay) on normal (Vero) and cancerous cell lines (MCF-7) and genotoxicity by the comet assay. The spherical-shaped curcumin zinc oxide nanoparticles of 189 nm size were prepared with characteristic functional groups. The selectivity index of curcumin zinc oxide nanoparticles, calculated from IC50 values, is 4.60 > 2.0, showing anticancer potential comparable to tamoxifen. The genetic damage index of the highest concentration (40 µg/mL) of curcumin zinc oxide nanoparticles was 0.08, with a percent fragmentation of 8%. The results suggest that nanoparticles of curcumin zinc oxide produced better anticancer effects and did not cause any significant damage to the DNA. Consequently, further research is required to ensure the development of a safe and quality dosage form of nanoparticles for proper utilization.

Protective Effects of Dexmedetomidine Infusion on Genotoxic Potential of Isoflurane in Patients Undergoing Emergency Surgery.

Background: Isoflurane (ISO) has been extensively uses in general anesthesia and reported to cause deoxyribonucleic acid (DNA) damage in prolonged surgical procedures. Dexmedetomidine (DEX) is an adrenergic agonist and having antioxidant activity that may reduce the genotoxic potential (DNA damage) and oxidative stress induced by ISO in patients undergoing major neurosurgical procedures. Methods and Findings. Twenty-four patients of ASA (American Society of Anesthesiologists) classes I and II were randomly divided into two groups (n = 12). Group A patients received ISO, while group B patients received DEX infusion for maintenance of anesthesia. Venous blood samples were collected at different time intervals and used to evaluate the oxidative stress marker malondialdehyde (MDA) and endogenous antioxidants superoxide dismutases (SOD) and catalases (CAT). A single-cell gel electrophoresis (SCGE)-comet assay was used to investigate the genotoxic potential of ISO. Conclusion: Increased level of antioxidants and decreased value of MDA and genetic damage index were seen in group B (P < 0.001) in a time-dependent manner. Genetic damage was highest at point T 2 (0.77 vs. 1.37), and continued to decrease till T 3 (0.42 vs. 1.19), with respect to negative controls or baseline values following DEX infusion. Significantly, higher level of MDA was recorded in serum of group A (P < 0.001) as compared to group B (1.60 ± 0.33 vs. 0.03 ± 0.001). Enzymatic activities of CAT and SOD were significantly higher in group B than group A (10.11 ± 2.18 vs. 5.71 ± 0.33), (1.04 ± 0.05 vs. 0.95 ± 0.01), respectively. It may play a contributing role in daily anesthesia practice and improve the toxic effects on patients as well as anesthesia personnel. Trial Registration. Ethical Committee of Post Graduate Medical Institute (PGMI), Lahore General Hospital approved the use of humans in this study vide human subject application number ANS-6466 dated February 04, 2019. Furthermore, as the clinical trials required registration from an appropriate registry approved by World Health Organization (WHO), this trail also retrospectively registered at Thai Clinical Trials Registry (an approved WHO registry for clinical trials registration) under reference ID TCTR20211230001 on December 30, 2021.

Niclosamide Modulates the Cellular and Humoral Immune Response in Balb/c Mice.

BACKGROUND: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. OBJECTIVE: This study aimed to evaluate the impact of niclosamide on immune response of mice. METHODS: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages. RESULTS: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-ß1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner. CONCLUSION: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-ß1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.

Effect of nabumetone on humoral immune responses in mice / Efeito da nabumetona nas respostas imunes humorais em camundongos

Nabumetone is used to reduce the pain and inflammation in rheumatoid arthritis. In the current study, immunomodulatory effect of Nabumetone is investigated in mice. The control group was administered normal saline orally as placebo. Nabumetone was administered orally via gavage in two treatment groups at 14mg/kg.b.w. doses and 28mg/kgb.w., respectively. Haemagglutination (HA) assay, Jerne hemolytic plaque and mice lethality assays were applied. In HA assay, the titer was significantly decreased in Nabumetone treatment groups (P< 0.001). In Jerne hemolytic plaque formation assay, there was a significant reduction (P< 0.001) in number of plaques in Nabumetone treated groups when compared with control. In mice lethality assay, there was a significant difference in mortality ratio of mice in control and Nabumetone treated groups (P< 0.001). Therefore, it is concluded that Nabumetone suppresses the humoral immune response in mice.(AU)

A nabumetona é usada na redução da dor e inflamação da artrite reumática. No presente estudo, o efeito imunomodulador é investigado em camundongos. O grupo de controle recebeu solução salina via oral como placebo. Nabumetona foi administrada oralmente via gavagem em dois grupos de tratamentos com doses de 14mg/kg.b.w. e 28mg/kgb.w., respectivamente. Foram realizados ensaios de hemaglutinação (HA), placa hemolítica de Jerne e letalidade dos camundongos. No ensaio HA, o grau foi significativamente menor nos grupos de tratamento com nabumetoma (P< 0.001). No ensaio de formação de placa hemolítica de Jerne houve redução significativa (P< 0.001) no número de placas em grupos tratados com nabumetoma comparado ao controle. No ensaio de letalidade dos camundongos houve diferença significativa no grau de mortalidade de camundongos no grupo de controle e grupos tratados com nabumetoma (P< 0.001). Portanto, conclui-se que a Nabumetoma suprime a resposta imune humoral em camundongos.(AU)

Evaluation of immunomodulatory effects of lomefloxacin in mice

Lomefloxacin is a flouroquinolone antibiotic that is quite efficacious against many gram negative and gram positive pathogens. Lomefloxacin evince antibacterial effects by modifying DNA gyrase in gram negative pathogens and topoisomerase IV in gram positive pathogens. This study is designed to assess the immunomodulatory effects of lomefloxacin in male albino mice. Three doses of lomefloxacin 12.5 mg/kg, 25 mg/kg and 50 mg/kg were used and delayed type hypersensitivity assay, cyclophosphamide induced neutropenic assay, carbon clearance assay, heamagglutination assay and mice lethality test were performed to evaluate the effects of lomefloxacin on immune system of mice. DTH assay has depicted the significant immunosuppressant potential of lomefloxacin at 25 mg/kg and 50 mg/kg dose. Total leukocyte count have exhibited highly significant reduction (P<0.001) in leukocyte count after cyclophosphamide administration. Differential leukocyte count has shown significant (P<0.01) reduction in lymphocyte count, whereas, highly significant (P<0.001) increase in monocyte count and significant (P<0.05) increase neutrophil count has been observed. In carbon clearance assay, highly significant (P<0.01) increase in phagocytic index has been noted at 12.5 mg/kg and 25 mg/kg doses. Humoral immune system responses are suppressed in dose dependent manner by both heamagglutination assay (P<0.001) and mice lethality assay (P<0.001). Results clearly depict that lomefloxacin possess quite significant immunomodulatory potential

Preparation, characterization and pharmacokinetics of cyadox nanosuspension.

An increase in number of newly developed synthetic drugs displays bioavailability constraints because of poor water solubility. Nanosuspensions formulation may help to overwhelm these problems by increasing dissolution velocity and saturation solubility. In the present study, cyadox (Cyx) nanosuspension was successfully prepared by recrystallization based on acid-base neutralization combined with high pressure homogenization method using Polyvinylpyrrolidone K30 (PVP) as stabilizer. The nanosuspension had uniform particle distribution, excellent sedimentation rate and redispersibility. The nanosuspension significantly improved the solubility, dissolution and bioavailability. The saturation solubility of Cyx nanocrystal was higher than that of bulk Cyx and released the total drug in very short time. Further, pharmacokinetics of Cyx nanosuspension and normal suspension following oral administration was investigated in beagle dogs. Nanosuspension improved the bioavailability of Cyx which could be beneficial for intestinal bacterial infection in animals. Maximum concentration and area under concentration time curve were increased with particles size reduction which might give rise to pronounce fluctuations in plasma concentration and more intensified antibacterial effects. The terminal half-life and mean resident time of Cyx nanosuspension had also increased compared to normal Cyx suspension. In conclusion, nanosuspensions may be a suitable delivery approach to increase the bioavailability of poorly soluble drugs.

Integrated Transcriptional and Proteomic Analysis of Growth Hormone Suppression Mediated by Trichothecene T-2 Toxin in Rat GH3 Cells.

Chronic exposure to trichothecenes is known to disturb insulin-like growth factor 1 and signaling of insulin and leptin hormones and causes considerable growth retardation in animals. However, limited information was available on mechanisms underlying trichothecene-induced growth retardation. In this study, we employed an integrated transcriptomics, proteomics, and RNA interference (RNAi) approach to study the molecular mechanisms underlying trichothecene cytotoxicity in rat pituitary adenoma GH3 cells. Our results showed that trichothecenes suppressed the synthesis of growth hormone 1 (Gh1) and inhibited the eukaryotic transcription and translation initiation by suppressing aminoacyl-tRNA synthetases transcription, inducing eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and reducing eukaryotic translation initiation factor 5 a. The sulfhydryl oxidases , protein disulfide isomerase,and heat shock protein 90 (were greatly reduced, which resulted in adverse regulation of protein processing and folding. Differential genes and proteins associated with a decline in energy metabolism and cell cycle arrest were also found in our study. However, use of RNAi to interfere with hemopoietic cell kinase (Hck) and EIF2AK2 transcriptions or use of chemical inhibitors of MAPK, p38, Ras, and JNK partially reversed the reduction of Gh1 levels induced by trichothecenes. It indicated that the activation of MAPKs, Hck, and EIF2AK2 were important for trichothecene-induced growth hormone suppression. Considering the potential hazards of exposure to trichothecenes, our findings could help to improve our understanding regarding human and animal health implications.