LOOH Levels Research Articles

Sex differences in the correlation between lipids related to cardiovascular risk factors and small dense LDL particles in patients with type 2 diabetes.

Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2. The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence. An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001). The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk.

Synthesis and in Vitro Evaluation of CAPE Derivatives as Ferroptosis Inducers in Triple Negative Breast Cancer.

Herein, we describe the design, synthesis, and in vitro biological evaluation of HO-1 inducers endowed with cytotoxic effects mediated by ferroptosis activation. Using the natural HO-1 inducer caffeic acid phenethyl ester (CAPE) as a chemical scaffold, new derivatives were synthesized by performing modifications in the cathecol moiety and in the phenethyl ester aromatic ring. Biological assays aimed at evaluating an imbalanced activity of ferroptosis key players identified that 2-(1H-indol-3-yl)ethyl cinnamate (compound 24) possesses improved anticancer activity toward the MDA-MB 231 triple negative breast cancer cell line when compared to CAPE. Increased ROS and LOOH levels, reduced GSH levels, imbalanced mitochondrial activity, and restored cell viability after ferrostatin-1 treatment suggested a ferroptotic mechanism of action, which did not involve GPX4 inhibition. Compound 24 represents an intriguing hit compound useful for the identification of novel ferroptosis inducers.

Evaluation of Atherosclerotic Risk by Oxidative Contributors in Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a condition described as the inability to control or stop alcohol consumption. The patients with AUD have an increased risk of developing atherosclerosis-related diseases. The present study aimed to evaluate oxidative contributors of atherosclerotic risk factors in patients with AUD. The male subjects diagnosed with AUD (n = 45) and the male subjects as control (n = 35) were enrolled in this study. All participants were undergone psychiatric evaluation and sociodemographic tests. Also, serum oxidative contributors of atherosclerosis including myeloperoxidase (MPO), ferroxidase, catalase (CAT), and lipid hydroperoxides (LOOH) were measured. Additionally, serum lipid profile tests and atherogenic indicators including atherogenic index of plasma (AIP) and non-high-density lipoprotein (HDL) cholesterol were also analyzed. The AUD subject had significantly elevated MPO activity and LOOH levels with decreased antioxidant capacity. AIP and non-HDL cholesterol levels, the atherogenic indicators, were also higher in AUD group compared to the control group. We found the MPO activity and LOOH levels were positively correlated with AIP, non-HDL cholesterol levels, and amount of alcohol consumption. Additionally, CAT activity was negatively correlated with duration of alcohol consumption. Our results revealed that MPO and LOOH levels were elevated by severe alcohol intake and the atherogenic indicators, AIP and non-HDL cholesterol, were significantly correlated alcohol induced elevated oxidative risk factors. Therefore, it can be suggested that MPO activity and LOOH levels may be useful to determine jeopardy of atherosclerotic and the therapeutic interventions that reduce oxidative load could be taken into account to prevent atherosclerotic diseases before clinical manifestation.

High-density lipoprotein dysfunction in carotid artery stenosis.

Background: High density lipoprotein (HDL) is well established to have an athero-protective role under normal conditions; however, pro-inflammatory alteration of HDL proteins may transform the HDL particle into a dysfunctional molecule. Our aim was to investigate HDL dysfunction by measuring enzyme-based markers in carotid artery stenosis (CAS). Patients and methods: All participants underwent duplex ultrasound and 52 subjects diagnosed with CAS and 51 subjects who had no significant stenosis (as controls) were enrolled in this study. Serum lipid profiles and serum parameters associated with dysfunctional HDL including myeloperoxidase (MPO), paraoxonase 1 (PON1), arylesterase (ARE) activity, and lipid hydroperoxide (LOOH) levels were measured. Results: It was found that the patients with CAS had increased levels of MPO and LOOH while PON1 activity was decreased. There was no significant difference between the CAS and non-CAS groups in terms of HDL levels. MPO/PON1, MPO/ARE, and LOOH/PON1 ratios were significantly increased in the CAS group. MPO/PON1 and MPO/ARE ratios both demonstrated significant correlations with degree of stenosis (%). Conclusions: The MPO/PON1 and MPO/ARE ratios may be potential serum markers that can enable the monitoring of HDL functionality and the assessment of atherosclerotic disease risks. Additionally, monitoring the oxidative balance of lipids on HDL molecules by LOOH/PON1 ratio may have value in the early detection of pro-atherosclerotic transformation of the HDL particle.

Danggui Shaoyao San: Chemical characterization and inhibition of oxidative stress and inflammation to treat CCl4-induced hepatic fibrosis

Ethnopharmacological relevanceDanggui Shaoyao San (DSS) has effective in treating hepatic ascites and liver disease. Aim of the studyTo explore the chemical characterization of DSS and protective effect on CCl4-induced hepatic fibrosis and its mechanism, especially its anti-oxidative stress and anti-inflammation. Materials and methodsThe chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. And the antioxidant activity of DSS in vitro was determined. The hepatic fibrosis model was established using intragastric administration of 40% CCl4/soybean oil (v/v) twice weekly for 13 weeks. From 6th week, the DSS group and the positive control group were given DSS (2, 4, 8 g/kg/d) and silymarin (50 mg/kg/d), respectively. The livers of rats were examined histologically by H&E. The ALT, AST, ALB and TBIL were determined, and hepatic fibrosis markers (HA, LN, CIV, PIIINP), oxidative stress (SOD, MDA, GST, GSH) and inflammatory factor (IL-6, TNF-α) were tested using ELISA kits. In addition, the levels of TAC, TOS, LOOH and AOPP in the liver were also determined. ResultsThe chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. The results show that DSS mainly includes triterpenoids, monoterpenes, phenols, sesquiterpenes, butyl phthalide, etc., and DSS has good antioxidant activity in vitro. In addition, the ALT, AST and TBIL of rats were remarkably reduced after treatment with DSS at three doses. Liver histopathological analysis showed that DSS alleviated the inflammatory infiltration, hepatocyte swelling, necrosis and hepatic fibrosis induced by CCl4. DSS significantly decreased HA, IV-C, PIIINP and LN. Further determination showed that DSS significantly increased TAC, OSI and decreased TOC, LOOH and MDA, indicating that DSS could regulate redox balance and reduce lipid peroxidation in vivo. DSS also increased the activity of GST, SOD and GSH concentration. In addition, DSS also reduced IL-6 and TNF-α. ConclusionsIn this study, we described the chemical characterization of DSS and found that it has good antioxidant activity. We proved that DSS has the functions of reducing oxidative stress, anti-inflammatory, protecting liver cells and reducing hepatic fibrosis.

THE EFFECT OF BROCCOLI SPROUTS ON OXIDATIVE STRESS MARKERS IN MICE FED WITH CAFETERIA DIET

The aim of our study was to determine the ability of broccoli sprouts to influence the intensity of lipid peroxidation in mice fed a high-calorie cafeteria diet. Materials and methods. In this study, C57BL/6J mice were used. For determinatiom of lipid peroxides (LOOH), we used a method based on the ability of lipid peroxides to convert Fe2+to Fe3+. Then Fe3+ forms a complex with xylenol orange that absorbs light at 580 nm at low pH. The reaction mixture contained coumene hydroperoxide (1 mM), FeSO4*7H2O(1 M), xylenol (4 mM), water and supernatant. Differences between groups were analyzed by Duncan’s test for multiple comparision. Results. During the experiment, we monitored the changes in body mass of mice fed with different diets. There were no differences in LOOH levels in cortexes of mice from all experimental groups, but there was a tendency to the lower content of LOOH in the brain of mice fed with cafeteria diet and broccoli. No statistical differences in levels of LOOH were found between groups, but LOOH levels tended to the highest in the groups fed with broccoli sprouts alone and cafeteria diet. A significant difference was observed in the muscles (C) between the broccoli sprout group and the cafeteria diet + broccoli group. We also found a significant difference between the group fed with the cafeteria diet and the cafeteria diet + broccoli, which may indicate protective effects of broccoli on lipid peroxidation on cafeteria diet. Conclusions. Mice fed with cafeteria diet and broccoli spouts had higher body mass than control mice fed with standard group. Hypothalamus of mice fed with standard diet with broccoli spouts or with cafeteria diet showed a tendency to higher LOOH levels, whereas no effects of the diets were found on cortexes LOOH levels. The cafeteria diet + broccoli group had the lowest muscle LOOH content compared to all other groups. Also, LOOH levels tended to be lower in the cortexes in the hypothalamus of mice fed with cafeteria diet + broccoli as compared with the cafeteria diet group. This suggests the potential protective effects of broccoli spouts.

A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs.

5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs.

Aortic ischemia-reperfusion injury and potency of fluoxetine.

Due to cross-clamping of the aorta during aortic aneurysm surgeries, ischemia-reperfusion (IR) develops, and it may cause damage to the aorta itself or even to remote organs by oxidative stress or inflammation. Fluoxetine (FLX) which might be used in the preoperative period for its tranquilizing effect also has antioxidant effects in short-term use. The purpose of our study is to examine whether FLX protects aorta tissue, against the damage caused by IR. Three groups of Wistar rats were formed randomly. 1) Control group (sham-operated), 2) IR group (60 min ischemia+120 min perfusion), and 3) FLX+IR group (FLX dose was 20 mg/kg for 3 days IP before IR). At the end of each procedure, aorta samples were collected, and oxidant-antioxidant, anti-inflammatory, and anti-apoptotic status of the aorta were evaluated. Histological examinations of the samples were provided. Levels of LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA were found to be significantly increased in the IR group compared with control (P<0.05) and SOD, GSH, TAS, and IL-10 levels were significantly lower (P<0.05). FLX significantly decreased LOOH, MDA, ROS, TOS, MPO, TNFα, IL-1β, IL-6, NF-kB, MMP-9, caspase-9, 8-OHdG, NO, and HA levels in the FLX+IR group compared with IR group (P<0.05) and increased IL-10, SOD, GSH, and TAS (P<0.05). FLX administration prevented the deterioration of aortic tissue damage. Our study is the first study that demonstrates FLX-mediated suppression of IR injury in the infrarenal abdominal aorta by antioxidant, anti-inflammatory, and anti-apoptotic properties.

Tobacco smoke induces oxidative stress and alters pro-inflammatory cytokines and some trace elements in healthy indoor cats.

This study was aimed to assess oxidative stress, pro-inflammatory cytokines and some trace elements in healthy pet cats exposed to environmental tobacco smoke. Forty healthy cats were included in this study. Cats were divided in two groups: Exposed to tobacco smoke (ETS; n = 20) and non-exposed to tobacco smoke (NETS; n = 20). Blood levels of cotinine, total oxidant status (TOS), oxidative stress index (OSI), lipid hydroperoxide (LOOH), protein carbonyl (PCO), advanced oxidative protein products (AOPP), total antioxidant status (TAS), copper, zinc-superoxide dismutase (Cu, Zn-SOD), catalase (CAT), total thiol (T-SH), interferon gamma (INF-γ), tumor necrosis factor (TNF-α), interleukin β (IL-1β), interleukin 6 (IL-6), interleukin-8 (IL-8), inter-leukin 2 (IL-2) and iron (Fe), zinc (Zn), copper (Cu), selenium (Se) levels were measured. Hematological and biochemical parameters were also measured. Serum cotinine, TOS, OSI, PCO, AOPP and LOOH levels were higher, whereas TAS and Cu, Zn-SOD levels were lower in ETS group. In ETS group INF-γ, IL-1β, IL-2, and IL-6 levels were higher. The Cu level was higher in ETS group. Blood reticulocyte number, serum creatinine and glucose were higher in ETS group. It could be concluded that exposure to tobacco smoke in cats impaired the oxidant/antioxidant balance and potentially triggered the release of pro-inflammatory cytokines.

Gastroprotective and gastric healing effects of the aqueous extract of Casearia sylvestris in rodents: Ultrasound, histological and biochemical analyzes

Ethnopharmacological importanceCasearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as “guaçatonga” or “erva-de-bugre.” Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. Aim of the studyThis study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. Materials and methodsRats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1β. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-β-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. ResultsThe AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1β, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. ConclusionThe results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.

Extract of Tagetes erecta L., a medicinal plant rich in lutein, promotes gastric healing and reduces ulcer recurrence in rodents

Ethnopharmacological relevanceTagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in South America to treat several ailments. Despite reports that T. erecta flowers are used in folk medicine to treat gastrointestinal diseases, there is no study regarding its gastric healing effects. Aim of the studyThe effect of dry extract of T. erecta L. (DETe) in gastric healing and gastric ulcer recurrence was evaluated, contributing to the validation of the antiulcer potential of this medicinal plant. MethodsRats were treated orally with vehicle (1 ml/kg), omeprazole (20 mg/kg), or DETe (3, 30 or 300 mg/kg) for 7 days, twice a day. The lesion area was evaluated, and the levels of reduced glutathione (GSH) and lipoperoxides (LOOH) and the activity of the superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and myeloperoxidase (MPO) were measured. The ulcer recurrence was evaluated in mice and induced by interleukin (IL)-1β (1 μg/kg, i.p). The recurred area, gastric wall thickness, GSH and cytokines levels, MPO and N-acetylglucosaminidase (NAG) activities were measured. ResultsDETe accelerated the healing of gastric ulcers only at 300 mg/kg, reducing the ulcerated area by 66%. In parallel, DETe reduced LOOH levels, SOD, CAT and MPO activities, while increasing GST activity and mucin amount. In the recurrence model, DETe reduced the lesion area by 94%, and in parallel decreased the gastric wall thickness and TNF levels, while increasing IL-10 amount. ConclusionsCorroborating the popular use of T. erecta, DETe favors the antioxidant system and reduce gastric inflammation, accelerating the gastric healing process and reducing the ulcer recurrence.

Cardioprotective properties of Artemisia herba alba nanoparticles against heart attack in rats: A study of the antioxidant and hypolipidemic activities

Recently, pharmaceutical scientists' interest has increased to find novel pharmaceutical natural substances with potent antioxidant capacity and very low side effects to be used safely in preventive medicine. One of the most common types of diseases with a large spread globally is cardiovascular diseases, which cause a high rate of deaths annually. The present study evaluated the use of Artemisia herba alba leaves’ extract (AHALE) and AHALE zinc oxide nanoparticles (AHALE–ZnONPs) against isoproterenol (ISO) inducing myocardial infarction (MI) in male rats. Several groups of Wistar male rats fed a high-fat diet (HFD) were pretreated with several doses of AHALE or AHALE–ZnONPs for one month followed by exposure to ISO for two days. After treatment, samples of the rats’ heart tissues and blood were collected for several molecular biological and biochemical analyses. Heart enzymes, antioxidant enzymes, lipid peroxidation compounds, lipid markers, activities, ROS generation, apoptosis, DNA damage and expression of lipid metabolism genes were analyzed in rats pretreated with AHALE or AHALE–ZnONPs followed by exposure to ISO. The results showed an increase in the levels of AST, ALT, LDH, CK, CK-MB, and cTnT (heart markers), elevation in TG, TC, and LDL levels (lipid profile markers), levels of TBARS and LOOH (lipid peroxidation products), ROS generation, DNA damage, apoptosis, and upregulation of PPAR-α, ADD1, FASN, and ACC genes in animals exposed to ISO in comparison with the control animals. Moreover, a decrease in antioxidant enzyme activities, including GPx, GRx, and GST, was observed in animals exposed to ISO in comparison with control rats. In male rats pretreated with AHALE or AHALE–ZnONPs followed by exposure to ISO, the oxidative stress induced by ISO was prevented. The results suggest that Artemisia extract could be considered for use as one of the natural compounds for prevention of atherosclerosis and heart diseases due to its high antioxidant and hypolipidemic activities. The reduced oxidative stress of Artemisia extract may be a result of the existence of flavonoids and phenolic substances.

The Effects of a Fermented Rapeseed or/and Soybean Meal Additive on Antioxidant Parameters in the Blood and Tissues of Piglets.

Simple SummaryThe use of fermented products, including fermented soybean meal, and recently also fermented rapeseed meal, in the diet of pigs and other animals is becoming increasingly popular. A diet containing protein components from which anti-nutrients and allergenic substances have been eliminated by means of fermentation stimulates beneficial gastrointestinal microflora, resulting in improvement in metabolic processes and thus improved animal health.The aim of the study was to assess the effect of fermented soybean meal (FSBM) and/or rapeseed meal (FRSM) on the redox status of blood and tissues in piglets. The experiment was conducted on 150 28-day-old weaned piglets divided into five groups. Piglets in the control group received standard diets with soybean meal. Animals in the experimental groups received diets in which a portion of the soybean meal was replaced with FRSM and/or FSBM: group FR—8% FRSM; group FR/FS—6% FRSM and 2% FSBM; group FS/FR—2% FRSM and 6% FSBM; and group FS—8% FSBM. Group FR/FS showed an increase in total antioxidant potential of plasma (FRAP) and low-molecular-weight antioxidants, i.e., vitamin C, urea, uric acid, and albumin, as well as an increase in catalase activity. Blood levels of lipid hydroperoxides (LOOH) and malonyl dialdehyde (MDA) were decreased. A reduction in lipid peroxidation due to the use of FR/FS was also indicated by a decrease in liver MDA and jejunum wall LOOH levels. Increases in superoxide dismutase (SOD) and catalase (CAT) activity and vitamin C levels in these tissues were also noted. The results of the study indicate that the inclusion of fermented rapeseed meal in the diet (6%) in combination with soybean meal (2%), improved the redox status of the weaners.

Addition of tea tree oil (Melaleuca alternifolia) in diet minimize biochemical disturbances in silver catfish Rhamdia quelen exposed to the antiparasitic amitraz

In the present study, we evaluated diets supplemented with Melaleuca alternifolia essential oil (tea tree oil - TTO) as a growth promoter and its possible hepatoprotective effects in Rhamdia quelen exposed to the insecticide amitraz. Six groups (8 per group, in triplicate) were tested: control A (basal diet), B (basal diet + TTO 1.0 mL/kg), C (basal diet +0.84 mL/kg amitraz), D (basal diet +1.19 mL/kg amitraz), E (basal diet +1.0 mL/kg TTO + 0.84 mL/kg amitraz) and F (basal diet + TTO 1.0 mL/kg + 1.19 mL/kg amitraz). Initially R. quelen received diets according to each group. After 14 days, four groups were exposed to two levels of amitraz for a period of 7 days, and were later transferred to amitraz-free water for recovery. We measured levels of reactive oxygen species (ROS) and lipoperoxidation (LOOH) in liver tissue, and activities of enzymes involved in energy metabolism, adenylate kinase (AK) and pyruvate kinase (PK), in addition to zootechnical indices such as length, weight body and fish weight gain. ROS and LOOH levels increased significantly (p < 0.05) in fish exposed to amitraz concentrations, especially in groups of fish not supplemented with TTO. By contrast, AK and PK enzyme activities were significantly lower (p < 0.05) for the groups exposed to amitraz compared to the unexposed group. Finally, fish supplemented with TTO showed better (p < 0.05) zootechnical performance. Addition of TTO minimizes biochemical disturbances in fish exposed to amitraz and serves as a natural additive to improve fish production.

ASSESSMENT OF TRACE ELEMENTS UPTAKE ON THE INVASIVE CRAB PORTUNUS SEGNIS HEPATOPANCREAS USING A MULTIVARIATE BIOCHEMICAL APPROACH

In the current investigation, we evaluated the biological consequences of trace elements contamination in the two Tunisian gulfs (Gabes gulf and Tunis gulf) on the blue swimming crabs hepatopancreas (Portunus segnis). The concentrations of three trace elements (cadmium, copper, and lead) in the hepatopancreas P.segnis were evaluated. Additionally, acetylcholinesterase (AChE), metallothioneins (MTs), hydroxide peroxidase (H2O2) and advanced oxidation protein products (AOPP) levels, were chosen as measurements to evaluate the environmental effects on the two crabs’ populations from different gulfs. Macromolecular (lipids, proteins, and DNA) were also determined in P.segnis hepatopancreas. The results of trace elements bioaccumulation in soft P. segnis hepatopancreas showed a high pollution in the Gabes gulf as evidence by significant accumulation of cadmium, cooper, and lead. These findings were confirmed by significant increases of metal pollution index (MPI) and metallothioneins (MTs) levels in the hepatopancreas of P. segnis from Gabes gulf than these from Tunis gulf. Consequently, the trace elements accumulation in P.segnis from Gabes gulf conduct to the generation of lipid peroxidation processes as documented by the high levels of H2O2and LOOH. A significant decrease of AChE activity was recorded in crabs collected from Gabes gulf as compared to these from Tunis gulf. The present study revealed depletion of proteins and lipids contents, while DNA showed significant degradation on crab hepatopancreas collected from Gabes gulf comparing to Tunis gulf. These evidences must be taken in consideration when using P. segnis as an ecological indicator species in the biomonitoring programs.

Low-density lipoprotein cholesterol-to-apolipoprotein B ratio as a potential indicator of LDL particle size and plasma atherogenicity in type 2 diabetes

AimsAtherogenic dyslipidemia, associated with small, dense low-density lipoprotein-cholesterol (S-LDL) particles and impaired metabolism of triglycerides (TGs) and high-density lipoprotein-cholesterol (HDL-c), leads to the development of atherosclerosis-related complications of type 2 diabetes mellitus. Based on the hypothesis that an LDL-c-to-apolipoprotein B ratio (LDL/ApoB) < 1.2 may predict the prevalence of S-LDL, this study aimed to evaluate the LDL/ApoB ratio in patients with type 2 diabetes with moderately elevated TG levels. MethodsThe study population consisted of 121 outpatients with type 2 diabetes (S-LDL group, LDL/ApoB < 1.2, n = 79; L-LDL group, LDL/ApoB > 1.2, n = 42) and 58 healthy subjects. The LDL/ApoB ratio was calculated from the measured LDL-c and ApoB levels in participants with TG levels lower than 4.5 mmol/L. Since TGs and HDL-c are included in the atherogenic index of plasma (AIP), we evaluated the relationship between LDL/ApoB and the AIP. ResultsHigher levels of AIP, TG (both P < 0.0001), and lipid hydroperoxides (LOOH) (P < 0.001) and lower levels of HDL-c, total cholesterol, and non-HDL-c (P < 0.001, <0.01, <0.05, respectively) were found in the S-LDL group compared to the L-LDL group. There were significant relationships between the LDL/ApoB ratio and the AIP, TG (both P < 0.0001), LOOH (P < 0.0005), and HDL-c levels (P < 0.05) in the S-LDL group. ConclusionsThe prevalence of S-LDL particles (65%) and the close association of LDL/ApoB with the AIP suggest that this ratio may be a potential indicator of increased cardiovascular risk in patients with type 2 diabetes.

Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats

Ionizing radiation leads to release of free radicals into the systemic circulation from irradiated tissues. These free radicals cause oxidative stress in distant organs. Oxidative status may be reversed by naturally occurring antioxidant agents. The aim of this study was to investigate protective and antioxidant effects of Nigella sativa oil (NSO) and thymoquinone (TQ) in kidney tissue of rats exposed to cranial irradiation. Forty-eight Sprague-Dawley rats were divided into six groups: IR group received irradiation (IR) to total cranium plus saline; IR plus NSO group received IR and NSO; IR plus TQ group received IR and TQ; sham group did not receive NSO, TQ or IR; control group of TQ received dimethyl sulfoxide; control group of NSO received saline. Total oxidant status (TOS), oxidative stress index (OSI) and lipid hydroperoxide (LOOH) levels were studied as oxidative parameters, and total antioxidant status (TAS), total sulfhydryl levels, paraoxonase (PON), ceruloplasmin (Cp) and arylesterase activities were determined as antioxidative parameters in the kidney tissue of rats. Kidney TOS, OSI and LOOH levels were significantly lower in IR plus TQ, IR plus NSO and sham groups compared to IR group (p < 0.001). TAS, PON and Cp activities in IR group were significantly lower compared to the control group (p < 0.001). PON and Cp activities were significantly higher in IR plus NSO and IR plus TQ groups compared to IR group (p < 0.001). In conclusion, free radicals generated by cranial ionizing radiation exposure cause oxidative stress in kidney. NSO and TQ exhibit protective and antioxidant effects against oxidative damage in rats.

Oxidatively modified low-density lipoproteins are potential mediators of proteasome inhibitor resistance in multiple myeloma.

Proteasome inhibitor (PI) therapy has improved the survival of multiple myeloma (MM) patients. However, inevitably, primary or acquired resistance to PIs leads to disease progression; resistance mechanisms are unclear. Obesity is a risk factor for MM mortality. Oxidized LDL (OxLDL), a central mediator of atherosclerosis that is elevated in metabolic syndrome (co-occurrence of obesity, insulin resistance, dyslipidemia and hypertension), has been linked to an increased risk of solid cancers and shown to stimulate pro-oncogenic/survival signaling. We hypothesized that OxLDL is a mediator of chemoresistance and evaluated its effects on MM cell killing by PIs. OxLDL potently suppressed the ability of the boronic acid-based PIs bortezomib (BTZ) and ixazomib, but not the epoxyketone-based PI carfilzomib, to kill human MM cell lines and primary cells. OxLDL suppressed BTZ-induced inhibition of proteasome activity and induction of pro-apoptotic signaling. These cytoprotective effects were abrogated when lipid hydroperoxides (LOOHs) associated with OxLDL were enzymatically reduced. We also demonstrated the presence of OxLDL in the MM bone marrow microenvironment as well as numerous granulocytes and monocytes capable of cell-mediated LDL oxidation through myeloperoxidase. Our findings suggest that OxLDL may be a potent mediator of boronic acid-based PI resistance, particularly for MM patients with metabolic syndrome, given their elevated systemic levels of OxLDL. LDL cholesterol-lowering therapy to reduce circulating OxLDL, and pharmacologic targeting of LOOH levels or resistance pathways induced by the modified lipoprotein, could deepen the response to these important agents and offer clinical benefit to MM patients with metabolic syndrome.

Clinical Utility of the Logarithmically Transformed Ratio of Triglycerides-to- High-Density Lipoprotein Cholesterol and Its Relationship with Other Atherosclerosis-Related Lipid Factors in Type 2 Diabetes

Background: Elevated triglyceride (TG) levels and reduced high-density lipoprotein-cholesterol (HDL-c) levels indicate lipid abnormalities, but their levels alone do not reflect the actual status of plasma atherogenicity and cardiovascular disease risk (CVD). TG and HDL-c levels directly affect the balance between plasma atherogenic and antiatherogenic factors, as well as values of the atherogenic index of plasma [AIP (logarithmically transformed ratio of TG-to-HDL-c)]. The aim of this study was to evaluate the AIP risk categories (an indicator of plasma atherogenicity) and the relationships of AIP with other atherosclerosis-related lipid parameters in patients with type 2 diabetes mellitus (T2DM) and their potential clinical utility. Methods: Standard lipid profile, AIP, and lipid hydroperoxides (LOOH) were investigated in 124 T2DM outpatients (mean age 52.7 ± 5.9 years) and 61 healthy subjects (mean age 50.9 ± 6.8 years). T2DM patients were subclassified according to the AIP risk category and glycemic control. Results: Higher levels of AIP, LOOH, and TG and lower HDL-c (all P < 0.0001) were observed in T2DM patients than in the control group. AIP positively correlated with LOOH, non-HDL-c, and the non-HDL/HDL ratio (all P < 0.0001). The TG level was strongly correlated with the LOOH level among T2DM patients (P < 0.0001). Conclusions: The close association of AIP with other atherosclerosis-related lipid factors reveals an increased plasma atherogenicity. AIP risk categories indicate the actual status of plasma atherogenicity and identify subjects who are at an increased atherogenic risk and the development of CVD. In this respect, AIP has a promising future in routine clinical practice.

Association of -94 ATTG insertion/deletion NFkB1 and c.*126G>A NFkBIA genetic polymorphisms with oxidative and nitrosative stress biomarkers in Brazilian subjects with Parkinson’s Disease

Parkinson's disease (PD) is a complex neurodegenerative disorder, resulting dopaminergic neuronal cell death in the substantia nigra. The disease is characterized by major motor impairment, being bradykinesia, rest tremor, rigidity and loss of postural reflexes the most common, while autonomic dysfunctions, sleep disturbances and psychiatric disorders are some of the wide range of non-motor symptoms. Several processes have been identified to be associated with disease development, such as mitochondrial dysfunction, oxidative/nitrosative stress and neuroinflammation. NF-κB is an important transcription factor that regulates several inflammatory elements and pathways, and polymorphisms on NFKB1 and NFKBIA genes can potentially influence redox balance towards a pro-oxidative frame, modulating disease progression. Evaluation of these polymorphisms in the redox status of PD subjects could provide new insights on the pathogenesis of this disorder. The study aimed to test associations of -94 in./del ATTG NFKB1 (rs28362491) and c.*126G > A NFKBIA (rs696) polymorphisms with PD development, and to test the influence of both polymorphisms on oxidative/nitrosative stress (OS/NS) parameters. A total of 110 Brazilian individuals were enrolled, being 55 subjects recruited from University Hospital of Londrina as the PD group, and 55 subjects matched for age, sex and ethnicity composed the healthy control (HC) group. NFkB1 and NFkBIA polymorphisms were genotyped by PCR-RFLP. Lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), sulfhydryl groups (SH), total radical trapping antioxidant parameter (TRAP) and paraoxonase-1 activity (PON-1) were assessed. Despite no association of polymorphisms on disease development was observed, in PD subjects the NFKB1 del/del genotype was associated with higher levels of LOOH, while NFkBIA GA and AA genotypes were associated with higher NOx levels, suggesting that NFkB plays a role in PD susceptbility. In conclusion, the prospect of genetic polymorphisms of elements involved in inflammation and OS/NS might be a new approach to unravel PD etiology.