Protein Carbonyl Levels Research Articles

Minocycline Protects Against Lipopolysaccharide-Induced Cognitive Impairment and Oxidative Stress: Possible Role of the CREB-BDNF Signaling Pathway.

The oxidative stress-induced dysregulation of the cyclic AMP response element-binding protein- brain-derived neurotrophic factor (CREB-BDNF) cascade has been linked to cognitive impairment in several studies. This study aimed to investigate the effect of minocycline on the levels of oxidative stress markers, CREB, and BDNF in lipopolysaccharide (LPS)-induced cognitive impairment. Fifty adult male Sprague Dawley rats were divided randomly into five groups. Group 1 was an untreated control group. Groups 2, 3, 4 and 5 were treated concurrently with LPS (5mg/kg, i.p) once on day 5 and normal saline (0.7ml/rat, i.p) or minocycline (25 and 50mg/kg, i.p) or memantine (10mg/kg, i.p) once daily from day 1 until day 14, respectively. From day 15 to day 22 of the experiment, Morris Water Maze (MWM) was used to evaluate learning and reference memory in rats. The levels of protein carbonyl (PCO), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay (ELISA). CREB and BDNF expression and density were measured by immunohistochemistry and western blot analysis, respectively. LPS administration significantly increased escape latency to the hidden platform with decreased travelled distance, swimming speed, target crossings and time spent in the target quadrant. Besides, the hippocampal tissue of LPS rats showed increased levels of PCO and MDA, decreased levels of CAT and SOD, and reduced expression and density of BDNF and CREB. Treatment with minocycline reversed these effects in a dose-dependent manner, comparable to the effects of memantine. Both doses of minocycline treatment protect against LPS-induced cognitive impairment by reducing oxidative stress and upregulating the CREB-BDNF signalling pathway in the rat hippocampus.

Cadmium-induced toxicity in Meretrix meretrix ovary is characterized by oxidative damage with changes in cell morphology and apoptosis-related factors

Cadmium (Cd) is one of the most common pollutants in the environment. It can cause irreversible tissue damage and apoptosis in invertebrates. This study investigated the relationship between Cd exposure and oxidative damage and apoptosis in the ovarian cell of the clam Meretrix meretrix. The clams were exposed to different concentrations of Cd2+ (0, 1.5, 3, 6 and 12 mg L−1) for 5 days, and the accumulated level of Cd2+ in the ovarian tissue, and the degree of oxidative damage, changes in morphology and the response of apoptosis-related factors in the ovarian cell were determined. The bioaccumulation of Cd2+ and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), protein carbonylation (PCO), and DNA-protein crosslinking (DPC) in the ovary were found to increase significantly when the clams were exposed to increasing concentrations of Cd2+. The structure of the ovarian tissue was severely damaged, and the ovarian cells displayed an irregular arrangement. The results of AO/EB staining and flow cytometry showed that the apoptotic rate of the ovarian cells increased with increasing Cd2+ concentrations. The activities of caspase-3, -8, -9, and the mRNA levels of p53, Bax and Caspase-3 in the ovary were also significantly increased. Furthermore, the level of p53 mRNA was positively correlated with the levels of MDA, PCO, DPC and ROS, but negatively correlated with the levels of total antioxidant capacity (T-AOC) and Bcl-2 mRNA. Taken together, these results indicated that Cd2+ exposure would result in oxidative damage and apoptosis for the ovarian cells, suggesting that Cd2+ toxicity could negatively affect the reproductive capacity of M. meretrix, thus threatening the reproductive development of the shellfish.

Активність цитозольних ензимів катаболізму ендогенних альдегідів у печінці щурів за умов різної забезпеченості раціону нутрієнтами

The research was conducted to study the activity of aldehyde dehydrogenase (EC 1.2.1.3) and aldehyde reductase (EC 1.1.1.21), the levels of TBA reactive substances and protein carbonyl derivates in the cytosolic fraction of rat liver under the conditions of different dietary sucrose and protein content. The animals were distributed into the 4 experimental groups: group I — animals receiving full-value semi-synthetic feed (control group); group II — animals on a low-protein diet (LPD); III group — animals on a high-sucrose diet (HS); IV group — animals on a low-protein and high-sucrose diet (LPD/HS). It was found that in animals under conditions of dietary protein deficiency, there was a two-fold increase in the levels of TBA reactive substances and protein carbonyl derivates in the liver cytosolic fraction against the absence of changes in the aldehyde reductase and aldehyde dehydrogenase activity. At the same time, in animals on a high-sucrose diet, there was a significant accumulation of the TBA reactive substances and carbonyl derivatives in the liver cytosolic fraction along with a 2–2.5-fold increase in both aldehyde reductase and aldehyde dehydrogenase activity. The maximum accumulation of the products of oxidative damage to proteins and lipids along with the insufficient activation of the enzymes ensuring their catabolism can be considered as one of the possible mechanisms of liver cell damage under conditions of the low-protein/high-sucrose diet. The obtained results open new prospects for future studies of the mechanisms of endogenous aldehydes detoxification and further development of a strategy for the correction of metabolic liver disorders under the conditions of nutrient imbalance.

Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver.

The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n=5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.

Garlic and allopurinol alleviate the apoptotic pathway in rats' brain following exposure to fipronil insecticide.

Fipronil can cause oxidative tissue damage and apoptosis. Our goal is to evaluate the antiapoptotic impact of garlic or allopurinol against fipronil neurotoxicity. Thirty-six mature male albino rats were separated into control, garlic aqueous extract (500 mg/kg), allopurinol (150 mg/L in their drinking water), fipronil (13.277 mg/kg), garlic+fipronil, and allopurinol+fipronil. Our results revealed that fipronil induced a significant increase in brain malondialdehyde, protein carbonyl levels as well as enzymatic antioxidant activities (superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase), but glutathione-S-transferase recorded a significant decrease as compared to the control. In addition, fipronil significantly up-regulated the brain pro-apoptotic (Bax) and caspase -3 mRNA gene expression and induced DNA fragmentation but caused down-regulation in anti-apoptotic (Bcl-2) mRNA genes expression. Interestingly, co-administration with garlic or allopurinol improved the lipid peroxidation, antioxidant disturbance, and apoptosis induced by fipronil in the brain tissues. In conclusion, garlic or allopurinol reduced fipronil-induced apoptosis and reduced oxidative tissue damage, most likely through enhancing the tissue antioxidant defense system.

Liver lipopolysaccharide binding protein prevents hepatic inflammation in physiological and pathological non-obesogenic conditions

Lipopolysaccharide binding protein (LBP) knockout mice models are protected against the deleterious effects of major acute inflammation but its possible physiological role has been less well studied. We aimed to evaluate the impact of liver LBP downregulation (using nanoparticles containing siRNA- Lbp) on liver steatosis, inflammation and fibrosis during a standard chow diet (STD), and in pathological non-obesogenic conditions, under a methionine and choline deficient diet (MCD, 5 weeks). Under STD, liver Lbp gene knockdown led to a significant increase in gene expression markers of liver inflammation (Itgax, Tlr4, Ccr2, Ccl2 and Tnf), liver injury (Krt18 and Crp), fibrosis (Col4a1, Col1a2 and Tgfb1), endoplasmic reticulum (ER) stress (Atf6, Hspa5 and Eif2ak3) and protein carbonyl levels. As expected, the MCD increased hepatocyte vacuolation, liver inflammation and fibrosis markers, also increasing liver Lbp mRNA. In this model, liver Lbp gene knockdown resulted in a pronounced worsening of the markers of liver inflammation (also including CD68 and MPO activity), fibrosis, ER stress and protein carbonyl levels, all indicative of non-alcoholic steatohepatitis (NASH) progression. At cellular level, Lbp gene knockdown also increased expression of the proinflammatory mediators (Il6, Ccl2), and markers of fibrosis (Col1a1, Tgfb1) and protein carbonyl levels. In agreement with these findings, liver LBP mRNA in humans positively correlated with markers of liver damage (circulating hsCRP, ALT activity, liver CRP and KRT18 gene expression), and with a network of genes involved in liver inflammation, innate and adaptive immune system, endoplasmic reticulum stress and neutrophil degranulation (all with q-value<0.05). In conclusion, current findings suggest that a significant downregulation in liver LBP levels promotes liver oxidative stress and inflammation, aggravating NASH progression, in physiological and pathological non-obesogenic conditions.

144 Carbonylated proteins and Ozone in atopic eczema

The effect of pollutants on atopic eczema (AE) has been controversial; with different proposed inflammatory mechanisms in skin such as the aryl hydrocarbon (AhR), JAK/STAT pathways, oxidative stress and Carbonylated proteins (CPs). It has been shown that CP levels are higher in dry skin and AE skin lesions. Tower Hamlets Eczema Assessment (THEA) is a clinical environmental study in Bangladeshi AE patients. Ambient exposure of THEA patients to commonly studied pollutants showed that long-term exposure to ground-level Ozone (O3) has the strongest association with eczema severity.

Impact of Arginine Therapy on Clinical Outcomes, Mitochondrial Function and Oxidative Stress in Children with Sickle Cell Disease Hospitalized with Vasoocclusive Pain Episodes: A Randomized Controlled Trial

Introduction: Vaso-occlusive pain episodes (VOE) are the leading cause of emergency department (ED) visits & hospitalization in patients with sickle cell disease (SCD). During SCD-VOE, patients develop an acute arginine (Arg) deficiency. Supplementation with Arg has shown opioid-sparing effects, improves blood pressure & cardiopulmonary function & decreases length of hospital stay. Though we have previously demonstrated that intravenous (IV) Arg improves mitochondrial (mito) function, the precise mechanisms by which Arg mediates these positive effects remain unclear. Objectives: To determine the role of IV Arg as adjuvant in the management of SCD-VOE Methods: Prospective single-center double-blind randomized controlled trial (RCT) of IV Arg (TID, up to 7 days) in children with SCD age 3-21 years hospitalized for VOE requiring IV opioids. Patients with significant liver/renal dysfunction or those previously enrolled were excluded. Subjects were randomized into 1 of 3 arms: 1) 100 mg/kg/dose Arg, standard dose (SD), 2) loading dose: 200 mg/kg followed by SD or 3) placebo. Demographics, total parenteral opioid (TPO) use (morphine equivalents, mg/kg) time to crisis resolution (time of study drug delivery to last IV opioid in hours), pain scores, patient reported outcomes (PROMIS) & mito function were obtained before treatment & at discharge. The primary outcome measure was TPO use between study arms. Hypothesis tests & unadjusted & covariate-adjusted fixed & mixed effects generalized linear regression models were used, as appropriate, to compare cross-sectional & longitudinal outcomes within & between randomization arms. This protocol utilized IND#66943 (Sponsor-Morris), registered with ClinicalTrials.gov (NCT02536170). Results: 1,548 patients were screened, 266 were eligible, 114 consented, & 108 were randomized. Safety results of this RCT have been previously reported (Reyes et al, Am J Hematol 2022). Demographics & clinical outcomes of subjects randomized by treatment arm are provided in Table 1. While statistically insignificant, there was a clinically relevant decrease in TPO & time to crisis resolution in both Arg arms compared to placebo. The placebo group required 45% higher TPO & experienced >15 hours longer mean time to crisis resolution compared to combined Arg-treated groups when adjusted for HU use, continuous age and sex. Among children <17 years, the placebo group (n=33) required 80% more TPO compared to combined Arg groups (n=57; p=0.075). No differences in ED vs discharge pain scores or patient/parent PROMIS reports across arms were found. Mito Complex V activity was higher (p=0.02) & protein carbonyl levels were lower (p=0.003) at ED visit in patients on Hydroxyurea (HU). Notably mito Complex IV & V activity increased significantly in both Arg arms while there was no change in the placebo group (Fig 1, p<0.001); protein carbonyl levels in platelet rich plasma decreased in both Arg groups (Fig 1, p<0.001), suggesting a decrease in oxidative stress that increased in the placebo arm (p=0.02). Greatest mito improvement occurred with Arg loading dose. Conclusion: Arg supplementation increases mito activity & decreases oxidative stress in children with SCD-VOE. This is the first report to suggest a HU-related impact on mito activity in SCD. Prior reports show that Complex V inhibition leads to increased mito oxidant production in platelets from SCD patients. Acute improvements in Complex IV & V function & decreased oxidative markers with Arg therapy are consistent with Arg-induced reductions in mito oxidant generation. Arg therapy improves symptoms associated with MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) suggesting an impact of Arg on mito activity that may be beneficial in SCD. Given emerging data supporting a link between mito function and pain, improved mito activity may mechanistically contribute to decreased pain & ultimately less opioid requirement with IV Arg treatment, as well as have further implications for improved metabolism and oxidative signaling in SCD. In this RCT, Arg therapy also demonstrated clinically relevant opioid-sparing & a decreased time to crisis resolution that was statistically insignificant. A larger sample size may elucidate potential differences; we are currently enrolling 360 children in an ongoing PECARN-endorsed multicenter Phase 3 RCT (SCD Treatment with Arg Therapy - STArT). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Postharvest H2O2 treatment affects flavor quality, texture quality and ROS metabolism of ‘Hongshi’ kiwifruit fruit kept at ambient conditions

The aim of this study was to investigate the effects of 0.5 M hydrogen peroxide (H2O2) on flavor, texture quality and reactive oxygen species (ROS) metabolism in harvested ‘Hongshi’ kiwifruit. Results demonstrated that H2O2 accelerated changes in flavor detected by electronic tongue (e-tongue) and electronic nose (e-nose). In addition, H2O2 treatment promoted fruit softening, as evidenced by an earlier increment in the activities of α-amylase, total amylase, pectin lyase, and pectin methylesterase. There were higher levels of superoxide anion (O2−) and protein carbonylation in H2O2-treated fruit, even though H2O2 prompted the activities of superoxide dismutase (SOD), and peroxidase (POD) during the initial storage but decreased the activities dramatically during later storage. These results indicate that H2O2 accelerates flavor formation and softening by regulating ROS metabolism in kiwifruit.

Inhibition of advanced glycation end products and protein oxidation by leaf extracts and phenolics from Chilean bean landraces

• Leaf extracts from six Chilean landraces of Phaseolus vulgaris were investigated. • Some 26 compounds were identified from the most active sample by HPLC-MS/MS. • Pearson’s analysis shows strong correlations between phenolics and AGEs inhibition. • Caffeoyl malic acid and rutin synergistically inhibit AGEs and protein oxidation. Phenolics can decrease the levels of advanced glycation end products (AGEs) from proteins, but their mechanisms in complex mixtures are poorly understood. Leaf extracts and the main phenolics from Chilean bean ( Phaseolus vulgaris ) landraces were assessed for their capacity to inhibit AGEs and oxidative modifications on bovine serum albumin incubated with glucose. The leaf extracts of six bean landraces decreased AGEs (fluorescent AGEs and carboxymethyl lysine) and oxidative (Kyn, Di-Tyr, protein carbonyls) modifications. Fluorescent AGEs were characterized by time-resolved techniques. The composition of the extracts was determined by HPLC-DAD-Q-TOF-MS/MS, and the main compounds were quantified by HPLC. Correlations between the levels of AGEs or protein carbonyls with the main phenolics suggested synergic effects of caffeoyl malic acid (CMA) and rutin. The synergic effect was evaluated using mixtures of rutin and CMA, showing a strong decrease in fluorescent AGEs and protein carbonylation compared with the pure single compounds, supporting this finding.

Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate

The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms. In this study, we found that TPP caused cytotoxicity on human skin keratinocytes (HaCaT) and significantly inhibited the proliferation and cell migration in a concentration-dependent manner. Additionally, HaCaT cells were sensitive to TPP-induced apoptosis. Reactive oxygen species production was induced with TPP, which increased the protein carbonylation and lipid peroxidation levels. Moreover, TPP inhibited proteasome activity and increased the accumulation of ubiquitinated proteins. Exposure to TPP significantly increased the HSP90, HSP70, GRP94 and GRP78 protein levels. Overall, our findings indicate that TPP may pose a risk to human health and contribute to the current understanding of the risks of TPP at the molecular level.

Integrated biomarker response index as an ally in the observation of metabolic biomarkers in muscle of Astyanax lacustris exposed to thermal variation

Temperature is an important factor that conditions the physiological responses of fish, generating a stressful condition when in non-ideal parameters. Thus, the objective was to evaluate metabolic aspects in the muscle of fish Astyanax lacustris submitted to thermal shock. The specimens were subjected to 2, 6, 12, 24, 48, and 96 h of exposure to 15 °C and 31 1 °C, with their respective controls 23 °C. At 15 °C there was a reduction in glycogenolysis in the initial periods indicated by changes in glycogen phosphorylase (GP), pyruvate and lactate. Subsequently, there was an increase in GP activity, pyruvate levels and hexokinase activity in the next time periods, suggesting an increase in energy demand. At 31 °C there was observed low need for the protein metabolism, indicated by reduction in the activity of aspartate aminotransferase and alanine aminotransferase. At 15 °C, initial periods show an increase in glutathione reductase activity and an increase in carbonylated protein levels, indicating induction of oxidative stress for muscle. At 31 °C, there was a punctual increase in reduced glutathione levels at 24 h. In addition, the integrated biomarker response index proved to be a good ally in the evaluation of a set of biomarkers, corroborating the results observed by the biomarkers individually. Thus, it is possible to conclude that the acute thermal shock affects the metabolism of A. lacustris muscle, which undergoes rearrangements to deal with temperature, where 15 °C is more stressful than 31 °C.

Interplay between long non-coding RNA MALAT1 and pyroptosis in diabetic nephropathy patients

Diabetic nephropathy (DN) the most common micro-vascular diabetic complication is the leading cause of end-stage renal disease worldwide. Diagnosis and treatment of DN in its early stage can effectively guard against its progression. Recently, pyroptosis a special type of lytic cell death and noncoding RNA were reported to have roles in early diagnosis and progression of DN. The present study aimed to evaluate the role played by long noncoding RNA (lncRNA) MALAT1, oxidative stress and pyroptosis in early detection of DN. Sixty Type 2 DM patients were included and divided according to urinary albumin-creatinine (UACR) ratio into normoalbuminuria and microalbuminuria groups beside 20 age and sex matched healthy volunteers as controls. Serum caspase 1 and interleukin 18 (IL18) levels were immunoassayed and MALAT1 expression was assessed by real-time PCR. Additionally, glycemic, redox and inflammatory status were assessed. MALAT1 expression, serum caspase1 level, IL18 level, myeloperoxidase activity, and protein carbonyl level were significantly increased in micro-albuinuria diabetic group when compared with diabetic normo-albuminuria group. Meanwhile, catalase activity was significantly decreased. Receiver operating characteristic (ROC) curve analysis revealed that IL18 had the highest sensitivity and diagnostic accuracy for detecting early microalbuminuria and incipient DN followed by caspase1and lastly MALALT1. ConclusionPyroptosis, impaired redox and altered MALAT1 expression could be an underlying mechanism for DN development. Moreover, MALAT1 expression, caspase 1 and IL 18 levels could be regarded as a potential biomarker for early prediction of DN.

New Insights into the Role of Alternating Temperatures and Cyanide in the ROS-Mediated Cardoon Seed Dormancy Termination

Physiological dormancy in wild cardoon (Cynara cardunculus var. sylvestris) can be terminated by achenes exposure to alternating temperatures, likely with the participation of reactive oxygen species (ROS). Cyanide is a natural compound that mediates seed dormancy removal in some plant species in association with oxidative signalling exerted by ROS. To date, no study has been conducted on the cyanide effect on ROS homeostasis during the germination of cardoon. Here, we showed that the addition of cyanide at low concentrations in dormant cardoon achenes promotes dormancy breakage at a constant temperature, speeds up germination to alternating temperatures and promotes ROS accumulation in embryonic axes of dormant achenes. The in-silico transcriptome analysis showed that the expression levels of transcripts of genes associated with ROS signalling and production, calcium signalling, gibberellins biosynthesis and cell wall loosening were significantly up-regulated at the alternating temperatures imbibition condition. In contrast, the expression of gene transcripts associated with the inhibition of germination, ABA biosynthesis and signalling were up-regulated at the constant temperature imbibition. However, no significant difference in lipid peroxidation or protein carbonylation levels was observed when achenes were imbibed at constant or alternating temperature conditions. These results suggest that dormancy termination triggered by alternating temperatures or cyanide could be mediated by ROS production and signalling in the cardoon embryonic axis, but this does not determine extensive protein carbonylation.

Whey protein protects liver mitochondrial function against oxidative stress in rats exposed to acrolein.

Acrolein (AC) is one of the most toxic environmental pollutants, often associated with incomplete combustion of petrol, wood, and plastic, oil frying, and tobacco smoking, that causes oxidative damage to DNA and mitochondria. Considering that little is known about the protective effects of whey protein (WP) against AC-induced liver toxicity, the aim of our study was to learn more about them in respect to liver mitochondrial oxidative stress, respiratory enzymes, Krebs cycle enzymes, and adenosine triphosphate (ATP). To do that, we treated Sprague Dawley rats with daily doses of AC alone (5 mg/kg bw in 0.9 % NaCl solution), WP alone (200 mg/kg bw, in 0.9 % NaCl solution), or their combination by oral gavage for six days a week over 30 days. As expected, the AC group showed a drop in glutathione levels and antioxidant, transport chain, and tricarboxylic acid cycle enzyme activities and a significant rise in mitochondrial lipid peroxidation and protein carbonyl levels. Co-treatment with WP mitigated oxidative stress and improved enzyme activities. Judging by the measured parameters, WP reduced AC toxicity by improving bioenergetic mechanisms and eliminating oxidative stress.

Organochlorine and organophosphorus pesticides may induce brain cancer through oxidative stress.

In this study, oxidative stress was investigated as the possible mechanism of action of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in primary brain tumors (PBT). The levels of seven OCP residues and enzymatic antioxidant biomarkers including erythrocyte acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and paraoxonase-1 (PON-1) along with non-enzymatic oxidative biomarkers including malondialdehyde (MDA), protein carbonyl (PC), total antioxidant capacity (TAC), and nitric oxide (NO) were measured in blood samples of 73 patients with PBT and 104 healthy controls. A significant association was found between farming activities and PBT (55% of patients were engaged in farming activities while 45% had no farming experience). The mean levels of β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 4,4 DDT, MDA, PC, NO, SOD, CAT, and GPx were significantly higher in PBT patients, whereas the levels of TAC, PON-1, and AChE were significantly lower in these patients. Regression analysis showed that PBT was correlated with β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, and 4,4 DDT. Based on these results, it can be concluded that OCPs and OPPs may play a role in PBT development through the formation of reactive oxygen species (ROS) and promoting oxidative stress.

The potential adverse effects of acrylamide on the oxidative stress response, fatty acids profile, and histopathological aspect of the Mediterranean Holothuria forskali respiratory tree.

Acrylamide (ACR), organic compound, has been widely used owing to its broad spectrum of chemical and industrial applications. This study aims at evaluating the response of the antioxidant defense system, fatty acid composition and histopathological aspect in the respiratory trees of Holothuria forskali against ACR exposure under laboratory conditions. Holothuries were exposed to 5, 10, and 20 mg L-1 ACR concentrations for 5 days. A significant increase in n-6 polyunsaturated fatty acids levels especially the arachidonic acid (ARA, C20:4n-6) and its precursor linoleic acid (LA, C18:2n-6) in ACR-treated organisms. Regarding the n-3 levels, eicosapentaenoic acid (EPA, C20:5n-3) levels were increased in treated groups despite an acute decrease in docosahexaenoic acid (DHA, C22:6n-3) levels was observed. Our results showed a significant increase in hydrogen peroxide, malondialdehyde, protein carbonyl, and metallothionein levels along with an alteration of the antioxidants status in all treated sea cucumbers. The exposure to ACR prompted the inhibition of Acetylcholinesterase activity in a concentration-dependent manner. The histopathological aspect was marked especially with the infiltration of coelomic cells which confirms our biochemical findings. Our study provided novel insights to create a link between redox status and fatty acid composition disruptions to better understand ACR-triggered toxicity.

Promising Phyto-Antioxidant Methanolic Extract from Canarium Odontophyllum Miq. (Dabai) Leaves against UVB Induced B164A5 Melanoma Cells as a Potential Skin Chemoprevention Agent

The high incidence and mortality of skin cancer along with the development of chemotherapy resistance have urged researchers to look into alternative strategies to combat cancer. Chemoprevention is one of the well-researched strategies using natural products. Canarium odontophyllum Miq. (dabai) is a local seasonal fruit that is mainly found in Sarawak, Malaysia. The leaves of the fruit harbor many medicinal useful phytochemicals that provide a new insight for chemoprevention. The present research has been planned to study the chemopreventive activity of methanolic extract of C. odontophyllum Miq. leaves on UVB induced B164A5 melanoma cells through its antioxidant profiles. The extract displayed statistically significant (p&lt;0.05) antioxidant activity by enhancing superoxide dismutase, SOD (1023.02 ± 106.74 U/mg protein) and catalase (0.12 ± 0.003 U/mg protein) activities compared to negative control. Low oxidative damage was also observed whereby the protein carbonyl and malondialdehyde levels were significantly reduced (p&lt;0.05), 1.69 ± 0.296 nmol/mg protein and 1.181 ± 0.03 nmol/mg protein respectively. In conclusion, the extract exhibited a promising skin cancer chemoprevention activity through its significant antioxidant activities. These findings evidently pave the path for further investigations in chemoprevention strategy.

The Protective Effect of Rheum Ribes L., and Quercetin on Protein Carbonyl Levels Against Carbon Tetrachloride-Induced Liver and Kidney Damage in the Rats

Objective: This study was designed to examine the potential protective effects of Rheum ribes L., and quercetin on protein carbonyl (PCO) in kidney and liver tissue, trace elements (Fe, Cu, Zn) and mineral (P) in serum samples in Wistar rats of carbon tetrachloride (CCl4)-induced oxidative damage. &#x0D; Methods: The 2, 4-dinitrophenylhydrazine (DNPH) method is the most reliable method widely used to measure carbonyl levels in proteins. In this study, the effect of Rheum ribes L. (Rr) and quercetin on protein carbonyl, trace elements (Fe, Cu, Zn) and mineral (P) levels against carbon tetrachloride (CCl4) mediated liver and kidney damage was investigated. For this purpose, 56 Wistar albino female rats weighing 200 ± 220 g were used. Groups were designed as: controls, 0.3 ml DMSO, 1 ml/kg olive oil, 1 ml/kg CCl4, 100 mg/kg Rr, 100 mg/kg quercetin, 100 mg/kg Rr+1 ml/kg CCl4 and 100 mg/kg quercetin+1 ml/kg CCl4 groups. &#x0D; Results: The results showed that the CCl4 group had significantly higher level of protein carbonyl (PCO) than the control, DMSO, olive oil, Rr and quercetin groups (p

Toluidine blue O directly and photodynamically impairs the bioenergetics of liver mitochondria: a potential mechanism of hepatotoxicity.

Toluidine blue O (TBO) is a phenothiazine dye that, due to its photochemical characteristics and high affinity for biomembranes, has been revealed as a new photosensitizer (PS) option for antimicrobial photodynamic therapy (PDT). This points to a possible association with membranous organelles like mitochondrion. Therefore, here we investigated its effects on mitochondrial bioenergetic functions both in the dark and under photostimulation. Two experimental systems were utilized: (a) isolated rat liver mitochondria and (b) isolated perfused rat liver. Our data revealed that, independently of photostimulation, TBO presented affinity for mitochondria. Under photostimulation, TBO increased the protein carbonylation and lipid peroxidation levels (up to 109.40 and 119.87%, respectively) and decreased the reduced glutathione levels (59.72%) in mitochondria. TBO also uncoupled oxidative phosphorylation and photoinactivated the respiratory chain complexes I, II, and IV, as well as the FoF1-ATP synthase complex. Without photostimulation, TBO caused uncoupling of oxidative phosphorylation and loss of inner mitochondrial membrane integrity and inhibited very strongly succinate oxidase activity. TBO's uncoupling effect was clearly seen in intact livers where it stimulated oxygen consumption at concentrations of 20 and 40μM. Additionally, TBO (40μM) reduced cellular ATP levels (52.46%) and ATP/ADP (45.98%) and ATP/AMP (74.17%) ratios. Consequently, TBO inhibited gluconeogenesis and ureagenesis whereas it stimulated glycogenolysis and glycolysis. In conclusion, we have revealed for the first time that the efficiency of TBO as a PS may be linked to its ability to photodynamically inhibit oxidative phosphorylation. In contrast, TBO is harmful to mitochondrial energy metabolism even without photostimulation, which may lead to adverse effects when used in PDT.