Correlation between ABCB1 gene polymorphisms, antiepileptic drug concentrations and treatment response

Aim: A possible molecular mechanism of clinically defined multidrug-resistant epilepsy involves drug efflux transporters such as P glycoprotein (P-gp), a member of the ATP-binding cassette subfamily B1 (ABCB1). We have investigated the prevalence of the C3435T, G 2677T/A, and T129C single-nucleotide polymorphisms in the promoter region of MDR1 gene, in Romanian epileptic patients

Effects of Curcumin Nanoparticles in Isoproterenol-Induced Myocardial Infarction

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction

Grape Pomace Polyphenols as a Source of Compounds for Management of Oxidative Stress and Inflammation—A Possible Alternative for Non-Steroidal Anti-Inflammatory Drugs?

Flavonoids, stilbenes, lignans, and phenolic acids, classes of polyphenols found in grape pomace (GP), were investigated as an important alternative source for active substances that could be used in the management of oxidative stress and inflammation. The benefic antioxidant and anti-inflammatory actions of GP are presented in the literature, but they are derived from a large variety of experimental in vitro and in vivo settings. In these in vitro works, the decrease in reactive oxygen species, malondialdehyde, and thiobarbituric acid reactive substances levels and the increase in glutathione levels show the antioxidant effects. The inhibition of nuclear factor kappa B and prostaglandin E2 inflammatory pathways and the decrease of some inflammatory markers such as interleukin-8 (IL-8) demonstrate the anti-inflammatory actions of GP polyphenols. The in vivo studies further confirmed the antioxidant (increase in catalase, superoxide dismutase and glutathione peroxidase levels and a stimulation of endothelial nitric oxide synthase -eNOS gene expression) and anti-inflammatory (inhibition of IL-1𝛼, IL-1β, IL-6, interferon-𝛾, TNF-α and C-reactive protein release) activities. Grape pomace as a whole extract, but also different individual polyphenols that are contained in GP can modulate the endogenous pathway responsible in reducing oxidative stress and chronic inflammation. The present review analyzed the effects of GP in oxidative stress and inflammation, suggesting that it could become a valuable therapeutic candidate capable to reduce the aforementioned pathological processes. Grape pomace extract could become an adjuvant treatment in the attempt to reduce the side effects of the classical anti-inflammatory medication like non-steroidal anti-inflammatory drugs (NSAIDs)

Investigating Potential Correlations between Calcium Metabolism Biomarkers and Periprocedural Clinical Events in Major Cardiovascular Surgeries: An Exploratory Study

Background: There is emerging but conflicting evidence regarding the association between calcium biomarkers, more specifically ionized calcium and the prognosis of intensive care unit (ICU) postoperative cardiac patients. Methods: Our study investigated the relationship between ionized calcium, vitamin D, and periprocedural clinical events such as cardiac, neurologic and renal complications, major bleeding, vasoactive–inotropic score (VIS), and length of ICU and hospitalization. Results: Our study included 83 consecutive subjects undergoing elective major cardiac surgery requiring cardiopulmonary bypass. The mean age of the participants was 64.9 ± 8.5 years. The majority of procedures comprised isolated CABG (N = 26, 31.3%), aortic valve procedures (N = 26, 31.3%), and mitral valve procedures (N = 12, 14.5%). A difference in calcium levels across all time points (p p = 0.016). On day 1, calcium levels were inversely associated with the duration of mechanical ventilation (r = −0.30, p = 0.007) and the length of hospital stay (r = −0.22, p = 0.049). At discharge, calcium was inversely associated with length of hospital stay (r = −0.22, p = 0.044). All calcium levels tended to be lower in those who died during the 1-year follow-up (p = 0.054). Preoperative vitamin D levels were significantly higher in those who experienced AKI during hospitalization (median 17.5, IQR 14.5–17.7, versus median 15.3, IQR 15.6–20.5, p = 0.048) Conclusion: Fluctuations in calcium levels and vitamin D may be associated with the clinical course of patients undergoing cardiac surgery. In our study, hypocalcemic patients exhibited a greater severity of illness, as evidenced by elevated VIS scores, and experienced prolonged mechanical ventilation time and hospital stays. Additional larger-scale studies are required to gain a deeper understanding of their impact on cardiac performance and the process of weaning from cardiopulmonary bypass, as well as to distinguish between causal and associative relationships

Curcumin Nanoparticles Protect against Isoproterenol Induced Myocardial Infarction by Alleviating Myocardial Tissue Oxidative Stress, Electrocardiogram, and Biological Changes

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects

Vitamin D Supplementation: Oxidative Stress Modulation in a Mouse Model of Ovalbumin-Induced Acute Asthmatic Airway Inflammation

Asthma oxidative stress disturbances seem to enable supplementary proinflammatory pathways, thus contributing to disease development and severity. The current study analyzed the impact of two types of oral vitamin D (VD) supplementation regimens on the redox balance using a murine model of acute ovalbumin-induced (OVA-induced) asthmatic inflammation. The experimental prevention group received a long-term daily dose of 50 µg/kg (total dose of 1300 µg/kg), whereas the rescue group underwent a short-term daily dose of 100 µg/kg (total dose of 400 µg/kg). The following oxidative stress parameters were analyzed in serum, bronchoalveolar lavage fluid (BALF) and lung tissue homogenate (LTH): total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde and total thiols. Results showed that VD significantly reduced oxidative forces and increased the antioxidant capacity in the serum and LTH of treated mice. There was no statistically significant difference between the two types of VD supplementation. VD also exhibited an anti-inflammatory effect in all treated mice, reducing nitric oxide formation in serum and the expression of nuclear factor kappa B p65 in the lung. In conclusion, VD supplementation seems to exhibit a protective role in oxidative stress processes related to OVA-induced acute airway inflammation

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation

The present study evaluated the anti-inflammatory and analgesic effects of conventional curcumin (cC) and curcumin nanoparticles (nC) associated with diclofenac sodium (D) in experimental acute inflammation (AI) induced by carrageenan administration. Seven groups of eight randomly selected Wistar-Bratislava white rats were evaluated. One group was the control (C), and AI was induced in the other six groups. The AI group was treated with saline solution, the AID group was treated with D, the AIcC200 and AInC200 groups were treated with cC and nC, respectively, while AIcC200D and AInC200D were treated with cC and nC, respectively, both associated with D. Conventional curcumin, nC, and D were administered in a single dose of 200 mg/kg b.w. for cC and nC and 5 mg/kg b.w. for D. Association of cC or nC to D resulted in significant antinociceptive activity, and improved mechanical pressure stimulation and heat thresholds at 3, 5, 7 and 24 h (p < 0.03). The association of cC and nC with D (AIcC200D and AInC200D groups) showed significantly lower plasma and tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) up to 2.5 times, with the best results in the group who received nC. Moreover, AInC200D presented the least severe histopathological changes with a reduced level of inflammation in the dermis and hypodermis. The combination of nC to D showed efficiency in reducing pain, inflammatory cytokines, and histological changes in acute inflammation

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. Materials and methods: We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. Results: There was a significant difference (p &lt; 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p &lt; 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p &lt; 0.001). Conclusions: PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases