Effect of tangeretin on cisplatin-induced oxido-inflammatory brain damage in rats.

Cisplatin (CIS) is a platinum-derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti-inflammatory properties, in cisplatin-induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), IL-6 and IL-10 were measured to determine inflammatory activity. In addition, 8-OHdG and caspase-3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF-α, IL-1ß and IL-6 obtained in CIS-treated groups increased as well as IL-10 decreased, thereby elevating the inflammatory response. In addition, 8-OHdG and caspase-3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity-induced apoptosis. This study shows that tangeretin has beneficial effects on CIS-induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti-inflammatory properties of tangeretin.

Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Glioblastoma cell-derived exosomes induce cell death and oxidative stress in primary cultures of olfactory neurons. Role of redox stress.

BACKGROUND: Glioblastoma multiforme, described as glioblastoma, is a malignancy originating from glial progenitors in the central nervous system and is the most malignant subtype of brain tumors which attracted researcher's attention due to their high recurrence and mortality despite optimal treatments. In the study, we aimed to research whether glioblastoma-originated exosomes play a role in olfactory nerve cell toxicity. METHODS AND RESULTS: For this aim, exosomes obtained from U373 and T98G cells were applied to olfactory nerve cell culture at distinct doses. Then, glutathione (GSH), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT), total oxidant status (TOS) and Immunofluorescence analyzes were performed. We found that both glioblastoma-derived exosomes decreased cell viability in olfactory neurons with increasing doses. According to the obtained data, the olfactory neuron vitality rate was 71% in T98G-exosome, but the decrease in U373-exosome was more obvious (48%). In particular, the 100 µg/ml dose exacerbated oxidative stress by increasing TOS. It also increased cellular apoptosis compared to the control group due to LDH leakage. However, the results of GSH and TAS showed that antioxidant levels were significantly reduced. CONCLUSION: In the microenvironment of olfactory neurons, GBM-derived exosomes increased oxidative stress-induced toxicity by reducing TAC and GSH levels. Therefore, glioblastoma cells by induction of exosome-based stress support malignant growth.

Evaluation of presence of clone ST131 and biofilm formation in ESBL producing and non-producing Escherichia coli strains.

OBJECTIVE: Escherichia coli ST131 is a pandemic clone associated with multidrug resistance, starting with beta-lactamase production and fluoroquinolone resistance in the first place, leading to significant systemic infections. Clones that develop due to the frequency of antimicrobial resistance and the rate of spread in our country are important issues that need to be investigated. This study aims to investigate the incidence of ST131which is a "high-risk pandemic clone E. coli" in ESBL-producing and non-ESBL-producing strains, as well as their biofilm-forming abilities and antibiotic resistance rates. MATERIALS AND METHODS: A total of 86 E. coli isolates were used in the study. Bacterial identifications were performed by conventional and automated methods. The double disc synergy method was used to demonstrate the presence of ESBL. Molecular studies in all E. coli strains were performed by real-time PCR method. FINDINGS: 86 strains were studied, of which 83.72% were urine, 6.98% were wound, 4.65% were blood, and 2.33% were tracheal aspirate and sputum. 79.07% of these strains were ESBL-positive. 58.1% of the strains were female, whereas 41.9% were male patients, and the average age was 46.2. Out of 86 strains, 38.72% were ST131 positive, the H30 subclone was detected in 27.27% of them, and the H30-Rx subclone was detected in all of the H30 subclone positive strains. The presence of the ESBL resistance gene was detected at the rate of TEM 41.86%, SHV 37.21%, CTX-M 36.04%, and OXA 4.65%. Most commonly SHV gene (54.54%) was seen in ST131 clone-positive samples. Finally, while it was found that 48.83% of the strains formed biofilm by any method, biofilm formation was detected in 69.7% of the samples that were positive for the ST131 clone. RESULT: Our study can reveal the dramatic prevalence of the ESBL-producing E. coli strains along with the high-risk ST131 clone, the dominance of the H30Rx subclone of this risky clone, as well as the importance of the influence of resistance mechanisms along with resistance and biofilm.

Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo.

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression.

Epilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain. Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T80 ) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T80 ). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).

Vincristine combination with Ca+2 channel blocker increase antitumor effects.

In this study, it was aimed to determine the effects of Amlodipine, a calcium channel blocker and vincristine (VCR) an antineoplastic, on human neuroblastomas using different doses. The cytotoxicity assays of the study were performed using the MTT method depending on time and concentration. After obtaining the mixture (up to 85% for SH-SY5Y) and sufficient branches (cortex neurons), the cells were treated with amlodipine (10 µM) and vincristine (0.5, 1 and 2 µg) at different concentrations for 24 h. MTT assay was performed by the commercially available kit (Sigma Aldrich, USA). Cells were harvested, washed and stained with PI and Annexin V, respectively, according to the manufacturer's protocol (Biovision, USA). Than analyzes were carried out. The results were quite impressive. When amlodipine (10 µM) was administered alone there was little change compared to the control. However, all doses of amlodipine (10 µM) and vincristine (0.5, 1 and 2 µg) were greater than the deaths in the doses alone (0.5, 1 and 2 µg) of vincristine alone. (P < 0.05). As a result, the combination of vincristine and amlodipine is more effective than vincristine alone in reducing the viability of cancer cells.

Cytotoxic effects of new-generation bulk-fill composites on human dental pulp stem cells.

This study was performed to evaluate possible DNA damage in cells of human origin exposed to dental composites in vitro using a cytotoxic assay. Five bulk-fill composites were filled in molds and irradiated for 20 s. DPSCs were inoculated into 24-well plates. After the insert membrane was inserted and composites were added and the experiment was continued for 24/72 hours. In order to investigate the effects of the materials on DPSCs; its effect on apoptosis-regulating Bcl-2 gene, Human Beta-Defensins (HBDs 1-2) gene, Interleukin 6, 8, 10 expression level was examined. Also in order to check the cellular viability and stress factors; MTT assay, Total Antioxidant and Oxidant Status kits were used. At both irradiation times, all composites significantly affected analyses parameters used in primary DNA damage assessment or induced significant formation of cellular death. Cytotoxicity was detected in TE<SS<FBF<XB<VBF groups at 24 hour, and after 72 hour this sequence has changed.

Cytotoxic and biological effects of bulk fill composites on rat cortical neuron cells.

The aim of this study was to investigate potential cellular responses and biological effects of new generation dental composites on cortical neuron cells in two different exposure times. The study group included five different bulk-fill flow able composites; Surefil SDR Flow, X-tra Base Flow, Venus Bulk Flow, Filtek Bulk Flow and Tetric-Evo Flow. They were filled in Teflon molds (Height: 4 mm, Width: 6 mm) and irradiated for 20 s. Cortical neuron cells were inoculated into 24-well plates. After 80% of the wells were coated, the 3 µm membrane was inserted and dental filling materials were added. The experiment was continued for 24 and 72 h. Cell viability measured by MTT assay test, total antioxidant and total oxidant status were examined using real assay diagnostic kits. The patterns of cell death (apoptosis) were analyzed using annexin V-FITC staining with flow cytometry. Β-defensins were quantitatively assessed by RT-PCR. IL-6, IL-8 and IL-10 cytokines were measured from the supernatants. All composites significantly affected analyses parameters during the exposure durations. Our data provide evidence that all dental materials tested are cytotoxic in acute phase and these effects are induced cellular death after different exposure periods. Significant cytotoxicity was detected in TE, XB, SS, FBF and VBF groups at 24 and 72 h, respectively.

Boron Compound-Based Treatments Against Multidrug-Resistant Bacterial Infections in Lung Cancer In Vitro Model.

Multidrug-resistant bacteria is one of the most important public health problems. Increasing rates of antibacterial resistance also affect the outcomes of medical approaches. Cancer treatment because of immune system deficiency (chemotherapy or steroids usage) commonly can cause infection. Lung cancer is the dominant cause of cancer-related deaths, and infection is the most common cause of death among those patients. In this study, it was aimed to determine the antimicrobial, antibiofilm, and anticancer activity of boron compounds. A549 lung cancer cell line was infected with Acinetobacter baumannii (ATCC 19606), Klebsiella pneumoniae (ATCC 700603), and Pseudomonas aeruginosa (ATCC 27853). In order to determine the fractional inhibitory concentration (FIC) index, antibiotics and boron compound concentrations prepared according to the minimum inhibitory concentration (MIC) values were determined by the checkerboard method. In our study results, the antibiofilm activity was an average of 46% in A. baumannii+boron compounds, 45% in P. aeruginosa+boron compounds, and 43% in K. pneumoniae. Cell culture analysis results show a decrease in viability and antioxidant capacity and an increase in total oxidant status after adding boron compounds to the culture. Immunofluorescence results show a correlation with MTT, and boron compounds increased 8-OHdG expression in comparison to antibiotic administration. In conclusion, boron compounds have promising effects on bacteria, especially in resistant bacteria spp.

Investigation of the miRNA levels changes to acceptable daily intake dose pesticide mixture exposure on rat mesentery and pancreas.

Consumers are constantly exposed to a variety of chemical mixtures as part of their everyday activities and lifestyle. Food, water and commercial products are only some examples of the possible ways people get exposed to these mixtures. However, following federal and local guidelines for risk assessment related to chemical exposure, risk analysis focuses on a single substance exposure scenario and not on a mixture, as in real life. Realizing the pronounced gap of this methodology, the real-life risk simulation scenario approach tries to address this problem by investigating the possible effect of long-term exposure to chemical mixtures closely resembling the actual circumstances of modern life. As part of this effort, this study aimed to identify the cumulative effects of pesticides belonging to different classes and commonly used commercial products on long-term exposure with realistic doses. Sprague Dawley rats were given a pesticide mix of active ingredients and formulation chemicals in a daily acceptable dose (ADI) and 10xADI for 90 days. Following thorough everyday documentation of possible side-effects, after 90 days all animals were sacrificed and their organs were examined. Exposure to pesticides particularly affects the miRNA levels at that point will provide us with more information about whether they can be potential biomarkers.

Glioma lateralization: Focus on the anatomical localization and the distribution of molecular alterations (Review).

It is well known how the precise localization of glioblastoma multiforme (GBM) predicts the direction of tumor spread in the surrounding neuronal structures. The aim of the present review is to reveal the lateralization of GBM by evaluating the anatomical regions where it is frequently located as well as the main molecular alterations observed in different brain regions. According to the literature, the precise or most frequent lateralization of GBM has yet to be determined. However, it can be said that GBM is more frequently observed in the frontal lobe. Tractus and fascicles involved in GBM appear to be focused on the corticospinal tract, superior longitudinal I, II and III fascicles, arcuate fascicle long segment, frontal strait tract, and inferior fronto­occipital fasciculus. Considering the anatomical features of GBM and its brain involvement, it is logical that the main brain regions involved are the frontal­temporal­parietal­occipital lobes, respectively. Although tumor volumes are higher in the right hemisphere, it has been determined that the prognosis of patients diagnosed with cancer in the left hemisphere is worse, probably reflecting the anatomical distribution of some detrimental alterations such as TP53 mutations, PTEN loss, EGFR amplification, and MGMT promoter methylation. There are theories stating that the right hemisphere is less exposed to external influences in its development as it is responsible for the functions necessary for survival while tumors in the left hemisphere may be more aggressive. To shed light on specific anatomical and molecular features of GBM in different brain regions, the present review article is aimed at describing the main lateralization pathways as well as gene mutations or epigenetic modifications associated with the development of brain tumors.

Activity of zinc oxide and zinc borate nanoparticles against resistant bacteria in an experimental lung cancer model.

BACKGROUND: Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties. OBJECTIVES: This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines. METHODS: Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis. RESULTS: The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL. CONCLUSION: A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.

Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study.

The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-ß (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.

AuNPs with Cynara scolymus leaf extracts rescue arsenic-induced neurobehavioral deficits and hippocampal tissue toxicity in Balb/c mice through D1R and D2R activation.

The present study was designed to evaluate whether AuNPs (gold nanoparticles) synthesized with the Cynara scolymus (CS) leaf exert protective and/or alleviative effects on arsenic (As)-induced hippocampal neurotoxicity in mice. Neurotoxicity in mice was developed by orally treating 10 mg/kg/day sodium arsenite (NaAsO2) for 21 days. 10 µg/g AuNPs, 1.6 g/kg CS, and 10 µg/g CS-AuNPs were administered orally simultaneously with 10 mg/kg As. CS and CS-AuNPs treatments showed down-regulation of TNF-α and IL-1ß levels. CS and CS-AuNPs also ameliorated apoptosis and reduced the alterations in the expression levels of D1 and D2 dopamine receptors induced by As. Simultaneous treatment with CS and CS-AuNPs improved As-induced learning, memory deficits, and motor coordination in mice assessed by water maze and locomotor tests, respectively. The results of this study provide evidence that CS-AuNPs demonstrated neuroprotective roles with antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as improving D1 and D2 signaling, and eventually reversed neurobehavioral impairments.

Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination.

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 - -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes.

Fe3O4 Nanoparticles in Combination with 5-FU Exert Antitumor Effects Superior to Those of the Active Drug in a Colon Cancer Cell Model.

(1) Background: Colon cancer is one of the most common cancer types, and treatment options, unfortunately, do not continually improve the survival rate of patients. With the unprecedented development of nanotechnologies, nanomedicine has become a significant direction in cancer research. Indeed, chemotherapeutics with nanoparticles (NPs) in cancer treatment is an outstanding new treatment principle. (2) Methods: Fe3O4 NPs were synthesized and characterized. Caco-2 colon cancer cells were treated during two different periods (24 and 72 h) with Fe3O4 NPs (6 µg/mL), various concentrations of 5-FU (4−16 µg/mL), and Fe3O4 NPs in combination with 5-FU (4−16 µg/mL) (Fe3O4 NPs + 5-FU). (3) Results: The MTT assay showed that treating the cells with Fe3O4 NPs + 5-FU at 16 µg/mL for 24 or 72 h decreased cell viability and increased their LDH release (p < 0.05 and p < 0.01, respectively). Furthermore, at the same treatment concentrations, total antioxidant capacity (TAC) was decreased (p < 0.05 and p < 0.01, respectively), and total oxidant status (TOS) increased (p < 0.05 and p < 0.01, respectively). Moreover, after treatment with Fe3O4-NPs + 5-FU, the IL-10 gene was downregulated and PTEN gene expression was upregulated (p < 0.05 and p < 0.01, respectively) compared with those of the control. (4) Conclusions: Fe3O4 NPs exert a synergistic cytotoxic effect with 5-FU on Caco-2 cells at concentrations below the active drug threshold levels.

Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence from an Animal Model.

BACKGROUND: Taxifolin (TXF) is a flavonoid found abundantly in citrus/onion. Encouraging results on its renoprotective effect have been reported in a limited number of drug-induced nephrotoxicity animal models. The present study aimed to evaluate for the first time the potential renoprotective effects of TXF in a paracetamol (PAR)-induced nephrotoxicity rat model. METHODS: Rats were divided into three equal groups (n = 6 animals per group). Group 1 (PAR group, PARG) received PAR diluted in normal saline by gavage (1000 mg/kg). Group 2 (TXF group, TXFG) received TXF diluted in normal saline by gavage (50 mg/kg) one hour after PAR administration. Group 3 (control group, CG) received normal saline. Twenty-four hours after PAR administration, all animals were sacrificed using high-dose anesthesia. Blood samples were collected and kidneys were removed. RESULTS: The serum blood urea nitrogen, creatinine levels and serum malondialdehyde levels were significantly increased in the PARG. The serum glutathione peroxidase, glutathione reductase and total glutathione levels were significantly higher in the TXFG. At the same time, the kidneys of the PARG animals demonstrated tubular epithelium swelling, distension and severe vacuolar degeneration. The kidneys of the TXFG animals showed mildly dilated/congested blood vessels. CONCLUSIONS: The TXF renoprotective effects are promising in preventing PAR-induced nephrotoxicity, mainly through antioxidant activity, and warrant further testing in future studies.

Carnosic Acid Ameliorates Indomethacin-Induced Gastric Ulceration in Rats by Alleviating Oxidative Stress and Inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, and erosions. Carnosic acid (CA) is an important natural antioxidant found in rosemary (Rosmarinus essentials) and exhibits a protective effect by suppressing oxidative stress and inflammation. This study aimed to investigate the impact of CA on IND-induced gastric ulceration. Wistar male rats received CA (100 mg/kg) or esomeprazole (ESP) (20 mg/kg, standard drug) by oral gavage for 14 days, after that gastric ulceration was induced by oral administration of 100 mg/kg IND. CA pretreatment attenuated both gross morphological lesions and histopathological alterations. CA strongly reduced IND-induced oxidative stress, verified by a decrease in MDA (p < 0.001) and TOS levels (p < 0.05). Furthermore, an IND-dependent increase in CAT (p < 0.001) and GPx (p < 0.01) activities, as well as a reduction in GSH levels (p < 0.01), were ameliorated by CA pretreatment. CA also attenuated inflammatory damage by suppressing IL-1ß (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) production and increasing Nrf2/HO-1 (p < 0.05) expressions. In conclusion, CA shows a gastroprotective effect by reducing oxidative stress and attenuating inflammation.