Increased Malondialdehyde Levels Research Articles

Genotype differences towards lead chloride harmful action

The aim of the study was to throw more light on the PbCl2 mode of action (MoA) depending on the genotype by the application of three model organisms and microbiological, biochemical, and molecular approaches. Three model systems – Chlamydomonas reinhardtii strain 137C – wild type (WT), Saccharomyces cerevisiae strain D7ts1, and Pisum sativum L. cultivar Ran1 and two experimental schemes – short- and long-term treatments were used. C. reinhardtii and S. cerevisiae cell suspensions (1×106 cells/ml) at the end of the exponential and the beginning of a stationary phase of growth were treated with various PbCl2 concentrations (0.45–3.6 mM) for 2 hours. Lower PbCl2 concentrations (0.03–0.22 mM) were also tested on C. reinhardtii 137C. Short-term treatment for up to 2 days with PbCl2 concentrations in the range of 0.45–3.6 mM and long-term treatment for up to 10 days with concentrations in the range of 0.45–2.7 mM was performed on P. sativum L. seeds and plants, respectively. Long-term treatment with a PbCl2 concentration of 3.6 mM was not tested because of the very strong toxic effect (plant death). The following endpoints were used – for C. reinhardtii: cell survival, “visible” mutations, DNA double-strand breaks (DSBs), malondialdehyde (MDA), intracellular peroxides (H2O2), and photosynthetic pigments; for S. cerevisiae – cell survival, gene conversion, reverse mutation, mitotic crossing-over, DSBs, superoxide anions, MDA and glutathione (GSH); P. sativum L. – germination and root length (short-term treatment), pro-oxidative markers – MDA, H2O2 and photosynthetic pigments (long-term treatment). Genotype differences between C. reinhardtii (0.047 mM) and S. cerevisiae (1.66 mM) were observed by two endpoints: concentrations inducing 50% lethality (LD50) and DSB induction. By contrast, no mutagenic effect was found for both unicellular test models. A slight toxic capacity of PbCl2, measured as inhibition of Pisum sativum L. seed germination and around 20% root length reduction was revealed after the treatment with concentrations equal to or higher than 1.8 mM. The variety of stress responses between the two plant test models was demonstrated by comparing MDA and H2O2. A dose-dependent increase in H2O2 levels and a minor increase of MDA levels (around 9–15%) were measured when C. reinhardtii cells were treated with concentrations in the range of LD20–LD80 (0.03–0.11 mM). Analyzing the kinetics of MDA and H2O2 in pea leaves, the most pronounced effect of concentration was shown for 2.7 mM. A decrease in the photosynthetic pigments was detected in the two experimental designs – short-term on C. reinhardtii and long-term on P. sativum treatments. The pro-oxidative potential was also proven in S. cerevisiae based on increased levels of MDA and superoxide anions and decreased GSH. New information is gained that PbCl2 can affect the DNA molecule and photosynthetic pigments via induction of oxidative stress. Our study revealed that the magnitude of stress response towards PbCl2 is genotype-specific. Our finding that Chlamydomonas reinhardtii is a sensitive test system towards PbCl2 contributes to good strategies for revealing very low levels of contaminants present chronically in main environmental matrices. This is the first report, as far as we know, affirming that PbCl2 can induce DSBs in Chlamydomonas reinhardtii and Saccharomyces cerevisiae.

Bifurcaria bifurcata extract exerts antioxidant effects on human Caco-2 cells

The present research study investigated the potential protective effect of Bifurcaria bifurcata extract on cell viability and antioxidant defences of cultured human Caco-2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (tert-BOOH). Aqueous extracts were firstly characterized in terms of total phenolic contents. Concentrations of reduced glutathione (GSH) and malondialdehyde (MDA), generation of reactive oxygen species (ROS), nitric oxide (NO) production, antioxidant enzymes activities [NADPH quinone dehydrogenase 1 (NQO1) and glutathione S-transferase (GST)], caspase 3/7 activity and gene expression linked to apoptosis, proinflammation and oxidative stress signaling pathways were used as markers of cellular oxidative status. B. bifurcata extract prevented the cytotoxicity, the decrease of GSH, the increase of MDA levels and the ROS generation induced by tert-BOOH. B. bifurcata extract prevented the significant decrease of NQO1 and GST activities, and the significant increase of caspase 3/7 activity induced by tert-BOOH. B. bifurcata extract also caused an over-expression of GSTM2, Nrf2 and AKT1 transcriptors, as well as reduced ERK1, JNK1, Bax, BNIP3, NFκB1, IL-6 and HO-1 gene expressions induced by tert-BOOH suggesting an increase in cellular resistance against oxidative stress. The results of the biomarkers analyzed show that treatment of Caco-2 cells with B. bifurcata extract enhance antioxidant defences, which imply an improved cell response to an oxidative challenge. B. bifurcata extract possesses strong antioxidant properties and may be a potential effective alternative to oxidant agents in the functional food industry.

Mitochondrial dysfunction, oxidative stress, ER stress and mitochondria-ER crosstalk alterations in a chemical rat model of Huntington's disease: Potential benefits of bezafibrate

Redox homeostasis, mitochondrial functions, and mitochondria-endoplasmic reticulum (ER) communication were evaluated in the striatum of rats after 3-nitropropionic acid (3-NP) administration, a recognized chemical model of Huntington’s disease (HD). 3-NP impaired redox homeostasis by increasing malondialdehyde levels at 28 days, decreasing glutathione (GSH) concentrations at 21 and 28 days, and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione S-transferase at 7, 21, and 28 days, catalase at 21 days, and glutathione reductase at 21 and 28 days. Impairment of mitochondrial respiration at 7 and 28 days after 3-NP administration was also observed, as well as reduced activities of succinate dehydrogenase (SDH) and respiratory chain complexes. 3-NP also impaired mitochondrial dynamics and the interactions between ER and mitochondria and induced ER-stress by increasing the levels of mitofusin-1, and of DRP1, VDAC1, Grp75 and Grp78. Synaptophysin levels were augmented at 7 days but reduced at 28 days after 3-NP injection. Finally, bezafibrate prevented 3-NP-induced alterations of the activities of SOD, GPx, SDH and respiratory chain complexes, DCFH oxidation and on the levels of GSH, VDAC1 and synaptophysin. Mitochondrial dysfunction and synaptic disruption may contribute to the pathophysiology of HD and bezafibrate may be considered as an adjuvant therapy for this disorder.

Clemizole hydrochloride, a potent TRPC5 calcium channel inhibitor, prevents cisplatin-induced nephrotoxicity in Spraque-Dawley rats.

Cis-diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis-induced nephrotoxicity. Rats were divided into the following groups: control;Cis (8 mg/kg);Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem. Kidney injury was detected by histopathological and biochemical analysis. Urine urea nitrogen (UUN), creatinine, urine neutrophil gelatinase-associated lipocalin (NGAL), serum catalase (CAT), and malondialdehyde (MDA) levels were determined by enzyme-linked immunosorbent assay. Total antioxidant status (TAS) and total oxidant status (TOS)were studied using a colorimetric assay. Nephrin, synaptopodin, and Rac family small GTPase 1(RAC1) expressions were detected by Western blot analysis. Cis was found to induce histopathological alterations, including tubular degeneration, congestion, hemorrhage, hyaline casts, glomerular collapse, and apoptotic cell death. Clem at a doseof 1 and 5 mg/kgattenuated histopathological alterations. UUN, creatinine, and NGAL levels increased in the Cis-administered group, while all doses of Clem decreased in those. CAT and TAS levels decreased, whileTOS and oxidative stress index levels increased in the Cis-treated group. A dose of 1 and 5 mg Clemshowed antioxidant effects against oxidative stress. Cis induced lipid peroxidation by increasing MDA levels. All doses of Clem reduced MDA levels. Nephrin and synaptopodin expressions were decreased by Cis, and all doses of Clem increased that. All doses of Clem successfully depressed RAC1 expression. Clem showed a highly ameliorating effect on toxicity caused by Cis by blocking TRPC5 calcium channels.

A combination of acidic electrolyzed water with modified atmosphere packaging improves quality of jujube during cold storage by enhancing antioxidant activity.

This study aimed to investigate the effects of a combination of acidic electrolyzed water (AEW) and modified atmosphere packaging (MAP) on the quality of jujube stored at 1±0.5°C for 40 days. Jujube was treated with AEW+MAP, AEW, and MAP, respectively, to identify an appropriate preservation method based on the changes of quality indicators, activities of antioxidant enzymes and nonenzymatic antioxidant systems, malondialdehyde (MDA) content, and cell membrane permeability. Results showed that the combined treatment maintained higher storage quality of jujube than the other threetreatments. The combined treatment significantly suppressed softening, weight, and color loss and maintained total soluble solid and titratable acidity. Moreover, the combined treatment improved antioxidant capacity showing high levels of nonenzymatic antioxidant systems (ascorbic acid and 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity), and the activities of antioxidant enzymes (ascorbate peroxidase, superoxide dismutase, and catalase). These effects remarkably suppressed the increase of MDA level and cell membrane permeability, thereby inhibiting oxidative damage and alleviating quality deterioration. Furthermore, kinetic model indicated that AEW+MAP decreased rate constant of quality deterioration. Principal component analysis also showed that AEW+MAP treatment alleviated quality deterioration, with higher comprehensive score than other treatments. In summary, AEW+MAP was an effective preservation method to maintain storage quality and delay postharvest senescence of jujube. PRACTICAL APPLICATION: In this study, a combination of acidic electrolyzed water (AEW) with modified atmosphere packaging (MAP) has been found to have effective preservation effects on jujube. AEW+MAP treatment improved quality of jujube during cold storage mainly by enhancing antioxidant capacity. The combined treatment may provide a new preservation technology for jujube.

Assessing the combined toxic effects of metaldehyde mollucide

The excessive use of metaldehyde in agriculture to combat mollusks endangers both the environment and non-target organisms. The aim of this study is to investigate the toxicity caused by metaldehyde in Alliumcepa with the help of physiological, cytogenetic, biochemical and anatomical parameters. Also, DNA fragmentation caused by metaldehyde in root tip cells was measured by the "Comet Assay" method. The control group was germinated with tap water and the application groups were germinated with 20 mg/L metaldehyde, 40 mg/L metaldehyde, 100 mg/L metaldehyde and 200 mg/L metaldehyde for 72 h. The results of the physiological parameters showed that metaldehyde had a growth-limiting effect in A.cepa, depending on the application dose. According to root elongation levels, the EC50 (effective concentration) value for metaldehyde was 60.6 mg/L in A.cepa. As the treatment dose increased, the incidence of micronucleus and chromosomal aberrations gradually increased while mitotic index decreased. Metaldehyde exposure induced damages such as sticky chromosome, fragment, unequal distribution of chromatin, reverse polarization, bridge, and multipolar anaphase. In addition, metaldehyde caused cell damage in epidermis and cortex, thickening of the cortex cell wall and flattened cell nucleus in root meristem. Increasing doses of metaldehyde application also increased malondialdehyde levels, superoxide dismutase and catalase activities. As a result, it has been determined that the toxicity of metaldehyde in plants is versatile and the A.cepa test material is a suitable biological indicator to determine this toxicity.

Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress

Paclitaxel (PTX) is widely used to treat a number of malignancies, although it has toxic side effects. Hesperidin (HES) has a wide range of biological and pharmacological properties, including anti-inflammatory and antioxidant abilities. This research aims to investigate the role of HES in PTX-induced testicular toxicity. For 5 days, 2 mg/kg/bw i.p. of PTX was administered to induce testicular toxicity. Rats were administered oral dosages of 100 and 200 mg/kg/bw HES for 10 days after PTX injection. The mechanisms of inflammation, apoptosis, endoplasmic reticulum (ER) stress, and oxidants were investigated using biochemical, genetic, and histological techniques. As a result of PTX administration, decreased antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities and increased malondialdehyde level were regulated, and the severity of oxidative stress was reduced. NF-κB, IL-1β and TNF-α levels, which are among the increased inflammation parameters caused by PTX, decreased with HES administration. Although AKT2 gene expression decreased in PTX administered rats, it was determined that HES administration up-regulated AKT2 mRNA expression. Anti-apoptotic Bcl-2 decreased with PTX administration, and apoptotic Bax and Caspase-3 increased while HES administration reverted these effects towards control level. As a result of toxicity, the increase in ATF6, PERK, IRE1α, GRP78 levels caused prolonged ER stress, and this activity was diminished with HES and tended to regress. While all data were evaluated, Paclitaxel caused damage by increasing inflammation, apoptosis, ER stress and oxidant levels in testicular tissue, and Hesperidin showed a protective effect by correcting the deterioration in these levels.

Alteration of Aquaporins 1 and 4 immunohistochemical and gene expression in the cerebellum of diabetic albino rat

Aquaporins (AQPs) are a family of transmembrane channel proteins. AQP1 and AQP4 are expressed in cerebellum amongst others. This study was designed to assess the effect of diabetes on AQP1 and AQP4 expression in cerebellum of rats. Diabetes was induced by a single intraperitoneal injection of Streptozotocin 45 mg/kg in 24 adult male Sprague Dawley rats. Six rats from control and diabetic groups were sacrificed at one, four, and eight weeks post diabetic confirmation. After eight weeks, measurement of malondialdehyde (MDA), reduced glutathione (GSH) concentrations, and cerebellar mRNA expression for AQP1 and AQP4 genes were performed. Immunohistochemical evaluation of AQP1, AQP4, and glial fibrillary acidic protein (GFAP) for cerebellar sections was performed for all groups. Diabetes caused degenerative changes in Purkinje cells with a significant increase in the cerebellar level of MDA and AQP1 immunoreactivity and a significant decrease in GSH level and AQP4 expression levels. However, the alteration in the AQP1 mRNA level was not statistically significant. GFAP immunoreactivity was increased in 8 W diabetic rats following its decrease in 1 W diabetic rats. Diabetes caused some alteration in the AQPs 1 and 4 expression in the cerebellum of diabetic rats which may contribute to diabetes-induced cerebellar complications.

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa.

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Oxidative stress involves phenotype modulation of morbid soreness symptoms in fibromyalgia

ObjectivesMuscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to...

Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes

Arsenic is widely available in the environment and arsenic toxicity is a public health problem of serious concern worldwide. Zingerone is a promising phytochemical with various pharmacological effects. In this study, the potential protective effect of zingerone against sodium arsenite (NaAsO2, SA) induced nephrotoxicity was investigated. Thirty-five male Sprague-Dawley rats were divided into five different groups as control, zingerone, SA, SA + zingerone 25, SA + zingerone 50. SA was administered alone at a dose of 10 mg/kg for 14 days or given 30 min before zingerone (25 mg/kg or 50 mg/kg) treatment. At the end of the experiment, the kidney tissues was examined biochemically, molecularly and microscopically. SA toxicity was associated with increased malondialdehyde level, whereas glutathione, superoxide dismutase, catalase, and glutathione peroxidase were decreased. Administration of SA caused inflammation in the kidney tissue by upregulation of NF-κB and IL-1β, TNF-α, IL-6, iNOS, COX-2, MAPK14, MAPK15, JNK. SA administration caused apoptosis in the kidney by upregulating caspase-3 and Bax levels and downregulating Bcl-2, and autophagy by activating beclin-1. Also, SA administration showed a suppressive effect on AKT2 and FOXO1 mRNA transcript levels. All these factors impair kidney function and increase creatinine and urea levels, resulting in pathological changes and a decrease in nephrin. Treatment with zingerone at doses of 25 and 50 mg/kg significantly reduced oxidative stress, inflammation, apoptosis and autophagy in kidney tissue. In addition, it was confirmed by histological evaluation as well as serum urea and creatinine levels that kidney damage due to SA toxicity can be modulated by zingerone administration.

Airborne Exposure of the Cornea to PM10 Induces Oxidative Stress and Disrupts Nrf2 Mediated Anti-Oxidant Defenses.

The purpose of this study is to test the effects of whole-body animal exposure to airborne particulate matter (PM) with an aerodynamic diameter of <10 μm (PM10) in the mouse cornea and in vitro. C57BL/6 mice were exposed to control or 500 µg/m3 PM10 for 2 weeks. In vivo, reduced glutathione (GSH) and malondialdehyde (MDA) were analyzed. RT-PCR and ELISA evaluated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inflammatory markers. SKQ1, a novel mitochondrial antioxidant, was applied topically and GSH, MDA and Nrf2 levels were tested. In vitro, cells were treated with PM10 ± SKQ1 and cell viability, MDA, mitochondrial ROS, ATP and Nrf2 protein were tested. In vivo, PM10 vs. control exposure significantly reduced GSH, corneal thickness and increased MDA levels. PM10-exposed corneas showed significantly higher mRNA levels for downstream targets, pro-inflammatory molecules and reduced Nrf2 protein. In PM10-exposed corneas, SKQ1 restored GSH and Nrf2 levels and lowered MDA. In vitro, PM10 reduced cell viability, Nrf2 protein, and ATP, and increased MDA, and mitochondrial ROS; while SKQ1 reversed these effects. Whole-body PM10 exposure triggers oxidative stress, disrupting the Nrf2 pathway. SKQ1 reverses these deleterious effects in vivo and in vitro, suggesting applicability to humans.

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24h SD (but not 4h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

Tartrate resistant acid phosphatases and osteodystrophy in chronic renal failure as related to oxidative stress: - tartrate resistant acid phosphatase is a proxidant

Objective: Oxidative stress has emerged as a constant feature of Chronic Renal Failure (CRF), this possibly helps to promote the progression and complications of CRF. This study aims to evaluate the relation of tartrate resistant acid phosphatase (TRACP) to oxidative stress in patients with End Stage Renal Disease (ESRD). Methods: Forty Iraqi patients with ESRD underwent hemodialysis and thirty seven healthy individuals were included in the present study. Several biochemical parameters such as lipid peroxidation through the concentration of malondialdehyde (MDA), [copper], [iron], [transferrin], [uric acid] and ceruloplasmin ferroxidase activity were measured in sera of control and ESRD patients. Results: The results revealed presence of a significant increase (P&lt; 0.001) in both [MDA] and uric acid level in sera of ESRD patients in comparison with that of the control group. Meanwhile a non-significant increase (P&gt;0.05) was found in copper concentration with a significant decrease (P&lt;0.001) in serum [iron], total iron binding capacity (TIBC),unsaturated iron binding capacity (UIBC), and [transferrin] of the patients group in comparison with that of the control group .Moreover no difference was observed in the saturation percentage of transferrin with iron between both groups and non-significant decrease in both the activity and the specific activity of ceruloplasmin ferroxidase (P &gt; 0.05) in sera of the patients group. Conclusion: we concluded that the increased of TRACP activity takes part in the measured oxidative stress (as indicated by the increased MDA level) in Iraqi patients with ESRD.

Ameliorative effect of sixteen weeks endurance training on biochemical and oxidative damage in high fat diet induced obese rats

Obesity is mainly caused by consumption of high fat diet (HFD) and a lack of physical activity. Physical activity is an efficient strategy to delay development of obesity. In this studyv we tried to evaluate attenuating properties of 16 weeks endurance training on plasma oxidative stress and some biochemical parameters in HFD induced obese rats. Twenty-four male Wistar rats were randomly divided into four groups: standard diet group (SD), standard diet with endurance training group (ESD), HFD group and HFD with endurance training group (EHFD). After sixteen weeks, plasma was prepared and evaluated for measurement of different parameters. The results showed that HFD significantly decreased the activities of superoxide dismutase (33.58%), catalase (26.51%) and glutathione S-transferase (22.77%), while endurance training increased these enzymes activities. However, exercise ameliorated the increased malondialdehyde level and depletion of glutathione. In addition, it significantly reduced the increased levels of liver enzymes activities and lipid profiles. These findings suggest that endurance training has found to have beneficial effects against HFD-induced oxidative damage through increasing reduced antioxidants levels and inhibition of lipid peroxidation due to its antioxidant property. Thus, it can be considered an interesting strategy for the management of obesity related diseases.

Maternal Exposure to Acephate Caused Nephrotoxicity in Adult Offspring Rats Mediated by Excessive Autophagy Activation, Oxidative Stress Induction, and Altered Epithelial Sodium Channel and Na+/K+-ATPase Gene Expression

This study examined how maternal exposure to acephate-an organophosphate-based insecticide-affected the renal development in rat offspring during adulthood. Virgin female Wistar rats were randomly allocated to three groups: group 1 (control) received sterile water; groups 2 and 3 were intragastrically exposed to low (14 mg/kg) and high (28 mg/kg) doses of acephate from day 6 of pregnancy until delivery, respectively. Further, the offspring of the adult female rats were euthanized in postnatal week 8. Compared with the controls, the adult rat offspring with exposure to low and high doses of acephate exhibited elevated plasma creatinine and blood urea nitrogen levels. Additionally, immunofluorescence analysis revealed the upregulation of autophagic marker genes (Beclin-1 and LC-3) in the acephate-treated rat offspring, thereby suggesting the induction of an autophagic mechanism. Notably, the increased malondialdehyde level, decreased glutathione level, and decreased superoxide dismutase and catalase activities confirmed the ability of acephate to induce oxidative stress and apoptosis in the kidneys of the rat offspring. This may explain the renal histopathological injury detected using hematoxylin and eosin staining. Furthermore, a reverse transcription polymerase chain reaction revealed that the mRNA expression levels of the Na+/K+-ATPase and the epithelial sodium channel (ENaC) genes were significantly higher in the kidney of female offspring than that of controls owing to acephate toxicity. However, there was no significant effect of acephate on the expression of NHE3 in the treatment group compared with the control group. Overall, the present findings suggest that oxidative stress caused by prenatal exposure to acephate causes nephrotoxicity and histopathological alterations in adult rat offspring, likely by actions on renal ENaC and Na+/K+-ATPase genes as well as the autophagic markers Beclin-1 and LC-3.

Triptonide Ameliorates Middle Cerebral Artery Occlusion-induced Cerebral Ischemic Damage in Rats via Regulation of In flammatory Response

Background Cerebral ischemic stroke is the second major cause of mortality worldwide that results in persisting disability and mental agony. Ischemic stroke is induced by the diminished blood circulation to the brain, which can be due to obstruction by arteriosclerosis, fibromuscular dysplasia, or thrombosis. Triptonide is a diterpene triepoxide, purified out of extracts of Tripterygium wilfordii Hook F, and is an emerging target against, for example, cancers and inflammatory insults. Materials and Methods Taking this into consideration, this study was designed to analyze the effect of triptonide on ischemic/reperfusion (I/R) cerebral infarction stroke rats. Results Our study showed that triptonide decreased the infarct volume and brain edema produced by I/R. Moreover, triptonide protected the rats from any neurological deficits, which were analyzed using a five-point scoring system, augmented antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione content, and lowered the activity of acetylcholinesterase. Triptonide also decreased the levels of pro-inflammatory cytokines such as interleukin-1 β (IL-1 β), TNF- α, and IL-6, while it augmented anti-inflammatory cytokines IL-10 and vascular endothelial growth factor. In this study, cerebral infarction stroke rats showed an increase in malondialdehyde levels. Triptonide preserved the normal brain architecture from various neurotoxic effects. Conclusion Thus, triptonide can be targeted for drug discovery in the future to protect against cerebral infarction stroke.

Modeling and optimization of malondialdehyde (MDA) absorbance behavior through response surface methodology (RSM) and artificial intelligence network (AIN): An endeavor to estimate lipid peroxidation by determination of MDA

AbstractOxidative stress (OS) associated with reactive oxygen species (ROS) attacks many biomolecules, leading to cell death, lipid peroxidation (LP), and physiological mechanism damage in the human body because of its reaction with nucleotides, membrane lipids, and proteins. Malondialdehyde (MDA) is one of the end products of polyunsaturated fatty acids peroxidation. The elevated level of MDA is widely known as a biomarker for the indirect measurement of OS during LP. Although several derivatizations' approaches and successful commercial kits are available, their analytical validity and reliability in clinical studies require further attention to obtain robust quantitation and high‐quality data. Also, re‐evaluation and development of new analytical methods with high sensitivity and selectivity in response to free MDA and total MDA, DNA and protein adducts are not well‐characterized. Here, response surface methodology (RSM) and artificial neural network (ANN) were proposed to model, predict, and optimize MDA detection. This paper introduced a novel, simple, and fast modeling method using a new reagent (para methoxy aniline or PMA) for the first time to convert MDA to an adduct which could be detectable by UV‐Vis spectroscopy. Based on the interactions between MDA and PMA at times and temperatures, RSM and artificial intelligence network (AIN) were then applied to forecast the absorbance rate of MDA‐PMA. The optimum mode for the highest absorbance rate of MDA‐PMA is at the temperature of 74.99°C with a PMA concentration of 499.87 μM and MDA concentration of 49.98 μM. The best structure with five hidden layers, including 5,5,5,9,4 neurons with the transfer function logsig for each layer, was selected for the MLP‐ANN model. The maximum error rate of the MLP‐ANN model was 2.08%.Our new approach is an improvement over existing assay kits, overcoming limitations such as time, temperature, and reliability with a bright future to target increased MDA level in human samples.

The potential mechanism underlying the hepatorenal toxicity induced by hymexazol in rats and the role of NF-κB signaling pathway.

Hymexazol (HML) is widely used in agriculture as a systemic fungicide and plant growth promoter. Humans are continuously exposed to HML via various routes. The liver and kidneys are essential organs for the detoxification, metabolism, and excretion of HML. However, data concerning the impact of HML on nontarget organisms are scarce. The present study aimed to determine the mechanism of dose-dependent hepatorenal toxicity of HML in rats. Twenty-one rats were divided into three equal groups that received the following treatments via oral intake daily for 14 days: group 1, normal saline; group 2, low dose of HML (1/80 LD50 ); group 3, high dose of HML (1/40 LD50 ). We weighed the rats at the beginning and the end of the experiment to record the weight gain in each group. The results showed that HML induced dose-dependent hepatorenal toxicity manifested by a significant increase in malondialdehydelevels, a decrease in total antioxidant capacity and reduced glutathione contents, and upregulation of the transcriptase levels of the nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) genes. The HML-exposed groups displayed various histopathological changes in both organs, with significant elevation of all serum liver and kidney biomarkers. In conclusion, HML produced hepatorenal toxicity in rats through oxidative stress that mediates the NF-κB signaling pathway in response to pro-inflammatory cytokines such as TNF-α and IL-1β. We advise limiting the use of HML in agricultural and veterinary practices and finding an alternative agent to avoid the human and animal health risks induced by HML exposure.

Role of Gender in the Protection Against Doxorubicin-Induced Oxidative Stress

Background: There are gender differences in the oxidation-reduction reactions. Doxorubicin (Dox) is a chemotherapeutic drug that can produce oxidative stress which may require prevention by antioxidants. Aim: The study aimed to investigate the gender-dependent changes in Dox-induced oxidative stress, and the protective effects of coenzyme Q10 (CoQ10). Materials and Methods: Rats were administered CoQ10 orally for 17 days. On day 13, some rats receiving CoQ10 received a single intraperitoneal dosage of Dox, whereas other rats received normal saline. Glutathione (GSH), malondialdehyde (MDA), and total anti-oxidant capacity (T-AOC) were measured in both genders of albino rats. Results: Dox significantly reduced both GSH and T-AOC levels and caused a significant increase in MDA. The administration of CoQ10 significantly prevented these changes. Dox caused a larger reduction in GSH in males than in females, while CoQ10 caused more protection in females. Dox caused a higher increase in MDA levels in males. Conclusion: Pre-treatments with CoQ10 may protect against Dox-induced oxidative stress, with gender-dependent variations in the extent of these Dox/CoQ10 effects.