Lipid Peroxidation Activity Research Articles

“Copper-loaded microplastics unleash endoplasmic reticulum stress-driven liver apoptosis in fish Channa punctatus”

The extensive use of plastics has led to significant microplastic pollution, posing threats to environmental and human health. Concerns are growing about the toxicity of microplastics (MPs) and their ability to adsorb contaminants like Copper (Cu2+). Therefore, this study investigated the effects of environmentally realistic concentrations of Polyvinyl Chloride (PVC)-MPs and Copper, both individually and together, with a particular focus on triggering Endoplasmic reticulum (ER) stress-driven apoptosis in the liver of Channa punctatus. Well-habituated fish were organized into four groups: Group I (Control), Group II (0.5 mg/L PVC-MPs), Group III (0.85 mg/L Copper), and Group IV (0.5 mg/L PVC-MPs + 0.85 mg/L Copper). The treatment period was 15, 30, 45 and 60 days. Various liver parameters were assessed according to standard protocols to understand the repercussions of intoxication. A significant (p < 0.05) increment in Reactive Oxygen Species (ROS) pointed to a substantial rise in oxidative stress. Enzymatic antioxidants like superoxide dismutase (SOD) and catalase (CAT) showed significantly (p < 0.05) elevated extents while reduced glutathione (GSH) levels significantly (p < 0.05) dropped in a duration-dependent pattern. Additionally, lipid peroxidation (LPO) activities surged significantly (p < 0.05), and notable hepato-structural disruptions were observed. The evidence of liver damage was further verified by a significant (p < 0.05) rise in concentrations of hepatic biomarkers viz. Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic Pyruvic Transaminase (SGPT), and Alkaline phosphatase (ALP). Moreover, ER-stress was validated through the increased intracellular calcium levels along with the heightened expression of grp78, chop, atf4, perk, eIF2α, and gadd34 in exposed groups. This intricate cascade subsequently elicited the activation of bax, caspase-3, caspase-9, and apaf-1, while modulation of bcl-2, thereby driving hepatocyte-apoptosis via ER-stress response in C. punctatus, a widely consumed food-fish. Our findings underscore the toxic threats of Copper-laden PVC-MPs to aquatic life and potentially the broader ecosystem.

LRRK2 regulates production of reactive oxygen species in cell and animal models of Parkinson's disease.

Oxidative stress has long been implicated in Parkinson's disease (PD) pathogenesis, although the sources and regulation of reactive oxygen species (ROS) production are poorly defined. Pathogenic mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are associated with increased kinase activity and a greater risk of PD. The substrates and downstream consequences of elevated LRRK2 kinase activity are still being elucidated, but overexpression of mutant LRRK2 has been associated with oxidative stress, and antioxidants reportedly mitigate LRRK2 toxicity. Here, using CRISPR-Cas9 gene-edited HEK293 cells, RAW264.7 macrophages, rat primary ventral midbrain cultures, and PD patient-derived lymphoblastoid cells, we found that elevated LRRK2 kinase activity was associated with increased ROS production and lipid peroxidation and that this was blocked by inhibitors of either LRRK2 kinase or NADPH oxidase 2 (NOX2). Oxidative stress induced by the pesticide rotenone was ameliorated by LRRK2 kinase inhibition and was absent in cells devoid of LRRK2. In a rat model of PD induced by rotenone, a LRRK2 kinase inhibitor prevented the lipid peroxidation and NOX2 activation normally seen in nigral dopaminergic neurons in this model. Mechanistically, LRRK2 kinase activity was shown to regulate phosphorylation of serine-345 in the p47phox subunit of NOX2. This, in turn, led to translocation of p47phox from the cytosol to the membrane-associated gp91phox (NOX2) subunit, activation of the NOX2 enzyme complex, and production of ROS. Thus, LRRK2 kinase activity may drive cellular ROS production in PD through the regulation of NOX2 activity.

ATF3 as a response factor to regulate Cd-induced reproductive damage by activating the NRF2/HO-1 ferroptosis pathway

Cadmium (Cd) has garnered significant attention due to reproductive toxicity in inducing ferroptosis. However, the specific mechanisms underlying Cd-induced germ cell ferroptosis remain poorly understood. This study aimed to systematically explore the molecular mechanisms of germ cell ferroptosis by investigating differential changes in transcription factors and proteins in male mice treated orally with CdCl2 (0.5 g/L) reaching postnatal day 60, alongside Leydig cell (TM3) and Sertoli cell (TM4) lines. Results demonstrated that Cd exposure led to increased iron overload and oxidative stress in mouse testes, disrupted intracellular mitochondrial morphology characteristic of ferroptosis. RNA sequencing revealed significant upregulation of Atf3 and Hmox1 in Cd-exposed germ cells, along with increased expression of ATF3 and HO-1. Intervention in ferroptosis or HO-1 effectively rescued cells from Cd-induced mortality by breaking the detrimental cycle between lipid peroxidation and HO-1 activation. Further findings showed that NRF2 and HO-1 expression was notably elevated upon ATF3 overexpression in TM3 and TM4 cells, activating the Keap1-Nrf2 pathway and triggering ferroptosis in testes, whereas NRF2 and HO-1 expression levels were reversed when ATF3 was silenced. This study provides novel insights into ATF3-mediated NRF2/HO-1 signaling in Cd-induced mitochondrial ferroptosis in testes, shedding light on the mechanisms underlying Cd-induced ferroptosis and testicular injury.

Tolerance and phytoremediation capacity of atrazine and S-metolachlor by two duckweeds.

The phytotoxicity and removal of atrazine and S-metolachlor in sterile duckweed systems were estimated in this study. Herbicides were added at environmentally relevant ranges: 0-400µg/L for atrazine or 0-200µg/L for S-metolachlor in systems with Spirodela polyrhiza or Lemna minor. Toxicity biomarkers, i.e., changes in plant biomass, surface area, chlorophyll fluorescence parameters, pigments, lipid peroxidation, protein concentration, and antioxidative enzyme activities in plants were estimated after 7days. S. polyrhiza (RGRbiomass-EC50 = 164.8µg/L) was more tolerant to atrazine than L. minor (RGRbiomass-EC50 = 101.0µg/L). Atrazine caused damage to photosystem II (ΦM), a reduction in electron transport between PSII and PSI (Φ'M), as well as disruption in energy distribution pathways (decrease in qPrel and increase in UQFrel), most prominently in L. minor. However, L. minor (RGRbiomass-EC50 = 128.9µg/L) was more tolerant to S-metolachlor than S. polyrhiza (RGRbiomass-EC50 = 15.5μg/L). The highest sensitivity of S. polyrhiza to S-metolachlor was attributed to a decrease in absorbed energy used in photochemistry (qPrel) and an increase in lipid peroxidation, indicating that S. polyrhiza plants were experiencing oxidative stress. Residual pesticide analysis in the water after seven days allowed us to conclude that plants were responsible for reducing up to 16.5% of atrazine and 28.7% of S-metolachlor in the duckweed system. S. polyrhiza showed higher atrazine phytoremediation capacity than L. minor. S. polyrhiza was more efficient at an environmentally relevant concentration of S-metolachlor (25μg/L) and L. minor at higher concentrations (200μg/L).

The Influence of Water Deficit on Dehydrin Content in Callus Culture Cells of Scots Pine

Under a water deficit, the protective proteins known as dehydrins (DHNs) prevent nonspecific interactions in protein and membrane structures and their damage, in addition to playing an antioxidant role. The DHNs of a widespread xerophytic species Scots pine (Pinus sylvestris L.) have been poorly studied, and their role in resistance to water deficits has not been revealed. In this paper, we have expanded the list of DHNs that accumulate in the cells of Scots pine under the conditions of water deficits and revealed their relationship with the effects of water deficits. In this investigation, callus cultures of branches and buds of Scots pine were used. A weak water deficit was created by adding polyethylene glycol to the culture medium. Under the conditions of a water deficit, the activity of catalase and peroxidase enzymes increased in the callus cultures. A moderate decrease in the total water content was correlated with a decrease in the growth rate of the callus cultures, as well as with an increase in the activity of lipid peroxidation. The accumulation of Mr 72, 38, and 27 kDa DHNs occurred in the callus cultures of buds, and the accumulation of Mr 72 and 27 kDa DHNs positively correlated with the lipid peroxidation activity. An increase in the content of DHNs was observed in cultures that differed in origin, growth indicators, and biochemical parameters, indicating the universality of this reaction. Thus, previously undescribed DHNs were identified, the accumulation of which is caused by water deficiency and is associated with manifestations of oxidative stress in the kidney cells of Scots pine.

Changes in masseter muscle structure, membrane lipid peroxidation and Ca-ATPase activity as effects of different local anesthetics.

Local anesthetics (LA) can cause undesired effects such as sustained contraction of skeletal muscles as a result of structural and functional changes. Proper skeletal muscle function is controlled by intracellular Ca2+ concentration and efficient energy (ATP) production, which is closely related to cell ultrastructure. Aim: The aim of this study was to identify the structural and functional changes caused by LAs. Materials and Method: Male Wistar rats weighing 200 to 250g were used (n:49). They were divided into seven groups. One group was not anesthetized or treated (Control). The other six groups underwent intramuscular (IM) anesthesia with xylazine 2% (0.05 ml) and ketamine 50 mg/ml (0.1 ml/100g rat weight), and one of the following was applied to the masseter muscle (MM): no further treatment (Anesthetic Control group, CA); 0.1ml physiological saline solution (group SF); Carrageenin (group Carr) 1% as positive control group; prilocaine (group Pri), mepivacaine (group Mepi); or articaine (group Arti) 0.3M, IM. The animals were euthanized by cervical dislocation one hour after treatment. The effects of the different anesthetics on the MM were evaluated histologically and by electronic microscopy (EM). Ca-ATPase and membrane lipid peroxidation (LPX) were evaluated in muscle homogenates under the same conditions as those used to prepare the histological sections. Results: In general, structural damage and increased muscle contraction were observed in tissues treated with anesthetics. The most extreme values of Ca-ATPase activity and LPX were observed in the positive control group (carrageenin). Results were analyzed by one-way ANOVA for multiple comparisons and Tukey's test (p < 0.05). Conclusions: The results suggest that in the short term, local anesthetics affect the muscle function and are associated to structural changes.

Effect of tetrapeptides KK1 and KK5 on the immunological parameters of rat spleen during passive smoking

One of the trends in experimental and clinical immunology is the creation of new immunomodulators aimed at correcting various variants of the pathology of the immune system. Of interest are non-toxic, hormone-free and protease-resistant tetrapeptides, homologue of the of adrenocorticotropic hormone fragment (15- 18). There is little data in the literature on the effect of the above immunomodulators on the immunological parameters of the rat spleen on xenobiotic exposure models, which makes research relevant in this aspect. For the first time, the effect of tetrapeptides with laboratory ciphers KK1 and KK5 on the immunological parameters of the spleen of 36 female Wistar rats with passive smoking was evaluated. The experimental rats were fumigated with tobacco smoke for 8 hours daily for 20 days. Synthetic tetrapeptides were administered intranasally at a dose of 40 micrograms per kg/day, starting from the 10th day of the experiment. It was found that the studied tetrapeptides had a unidirectional positive effect on the immunological parameters of the spleen of experimental animals with passive tobacco smoking. This was expressed in a tendency to restore the pool of cells with CD3, CD4, CD8, CD20 markers to the level of the control group, as well as spontaneous and induced cytokine production by splenocytes. The shifts in the parameters of the spleen identified in this work may be based on a number of possible causes. Firstly, passive smoke causes a stress response in rats, which is confirmed by previous studies on a similar model, on an increase in the level of stress hormones in the blood serum of Wistar rats. Secondly, the literature data indicate the activation of lipid peroxidation during smoking. Thirdly, it is known that under the action of tobacco smoke toxicants, the lymphoid cell line suffers the most, since their polyhydrooxidized metabolites accumulate in the bone marrow and lymphoid organs, causing hypoplasia of the central and peripheral organs of immunity. A visible sign of this phenomenon is a decrease in the cellularity in the spleen, which is established in this work. Considering that active and passive smoking causes hypoxia and increases lipid peroxidation, the use of tetrapeptides KK1 and KK5 as agents that improve the body’s adaptation to hypoxia and increase resistance to stress damage is justified. Thus, the tetrapeptides KK1 and KK5 have a positive immunomodulatory effect, reducing the toxic stress effects of passive smoking.

Unveiling the Anticarcinogenic Potential of Inula racemosa Hook. f. Root Extract Against DMBA-Induced Mammary Tumour in Sprague Dawley Rats.

The Himalayan plant Inula racemosa has medicinal properties and can be used to prevent or treat cancer. This is because it contains certain chemicals that are known to fight cancer cells with few or no side effects. I. racemosa has been used for this purpose for many years in traditional medicine and has shown promising results. The present study was crafted to explore the suppressive impacts on cellular proliferation of the root extract derived from I. racemosa via in vivo experimentation. I. racemosa (IR) root extract was tested at three different doses (100, 250, and 500 mg/Kg BW) for 18 weeks to assess its anti-neoplastic activity against mammary tumors in female rats. The assessment included various parameters such as hematological and biochemical indices, tumor parameters, oxidative stress analysis, gross and histopathological lesion determination, Masson's trichrome staining, immunohistochemical expression of Ki-67, MMP-9, and VEGF in mammary gland tissues, and molecular docking. The chemopreventive action of IR root extract was demonstrated by the inhibition of tumor parameters (tumor size and tumor volume), minimum changes in the liver (ALT, AST, and ALP) and kidney enzymes (BUN and creatinine), declined lipid peroxidation activity, decline gross, and histological changes in mammary gland tumors, reduced expression of KI-67, MMP-9, and VEGF and maximum binding affinity of isoalantolactone with VEGF through molecular docking. The study suggests that the active constituents (isoalantolactone and alantolactone) of I. racemosa roots have anti-neoplastic activity against mammary tumors, making them a valuable therapeutic regimen for the future.

Antioxidant and Cytoprotective Effects of Different Compounds on Cyclophosphamide-induced Nephrotoxicity

Abstract: Cyclophosphamide is a drug derived from nitrogenous mustards and is mainly indicated for the anti-neoplastic clinic. When it is metabolized in the liver, it produces acrolein, a cytotoxic metabolite capable of generating damage to the body. The oxidative, nitrative and nitrosative stress are responsible for mediating this side effect since the toxicity of the drug induces the production of reactive species of oxygen (ROS) and nitrogen (RNS). These radicals are unstable and react with other molecules that can result in cellular lesions such as lipid peroxidation, enzymatic inactivation, and excessive activation of pro-inflammatory genes, producing molecules such as malonaldehyde (MDA) and nitric oxide (NO), representing oxidative stress markers. One of the consequences of these mechanisms is nephrotoxicity. In contrast, some compounds have direct or indirect antioxidante action, which are the objects of this study: gallic acid, aminoguanidine, chrysin, hesperidine, naringin, morin-5'-sulfonic acid sodium salt and spirulina. All of them are responsible for the nephroprotective activity when administered during experiments in vitro or in vivo. Thus, this observational bibliographic research is characterized as qualitative descriptive and explanatory, since it focuses on analyzing the antioxidant properties of compounds with possible potentials to inhibit the nephrotoxicity induced by cyclophosphamide and describe the results, in addition to clarifying the biochemical activities involved in the process.

Regional use of extracellular microvesicles of mesenchymal stromal cells in acute necrotizing pancreatitis in an experiment

Background. The significance of the problem of treatment of acute pancreatitis is due to an increase in the incidence with an increase in the number of necrotizing forms, accompanied by a high incidence of severe complications and high mortality.Objective. To identify the impact of regionally used extracellular microvesicles of mesenchymal stromal cells on the endogenous intoxication markers in acute necrotizing pancreatitis in the experiment.Material and methods. Acute pancreatitis was induced by the introduction of a 0.3 ml of 5% solution of non-ionic polyethylene glycol octylphenol ether detergent into the caudal part of the rat pancreas. The study was conducted on 42 adult Wistar rats, which were randomly divided into 4 groups. Group I (n=6) included intact animals, Group II (control group) (n=12) included rats with pancreatitis without treatment, Group III (n=12) consisted of rats with pancreatitis treated with analgesia + infusions of 0.9% sodium chloride solution (saline), Group IV (n=12) included rats with pancreatitis treated with analgesia+ saline infusions + regional application of extracellular microvesicles of mesenchymal stromal cells. Cells were obtained from the bone marrow of healthy animals. Microvesicles were obtained by differential centrifugation under sterile conditions. Microvesicles were administered one day after the pancreatitis induction through the catheter installed into the pathologically altered part of the pancreas. The dose of microvesicles was calculated as equivalent to (derived from) 1 million mesenchymal stromal cells. The hematological parameters, markers of the systemic manifestation of the pathological process (alpha-amylase, aspartate aminotransferase, alanine aminotransferase), the endogenous intoxication markers (lipid peroxidation activity, nitric oxide level), the systemic inflammatory response markers (tumor necrosis factor-alpha, interleukin-6) were studied on the 3rd and 7th day from the start of disease modeling.Results. Regional use of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute experimental necrotizing pancreatitis at an early stage helped to normalize the level of blood platelets, reduce enzymeemia, elements of endogenous intoxication (interleukin-6, tumor necrosis factor-alpha), and the nitric oxide level.Conclusion. The early application of extracellular microvesicles of mesenchymal stromal cells in the treatment of acute necrotizing pancreatitis in an experiment has a positive effect on parameters, which are key links of pathogenesis and leading markers of this disease severity.

Ameliorative extract Syzygium cumini seed extract on lipid peroxidation and antioxidant activity in alloxan induced diabetic Wistar albino rats

Aim: This study intends to examine the protective effects of an aqueous extract of Syzygium cumini seed on lipid peroxidation and antioxidant enzyme activities in alloxan-induced diabetic Wistar albino rats. Methodology: A single intraperitoneal injection of 150 mg kg-1 b.wt of alloxan monohydrate was used to induce diabetes in rats. Syzygium cumini group rats were later administered 300 mg kg-1 of Syzygium cumini seed extract by oral gavage for 21 days. On 22nd day, the animals were given general anaesthesia, blood was drawn through the retroorbital plexus, and the kidneys were promptly removed. Lipid peroxidation levels were assessed in the blood (serum) and kidney tissues by measuring the thiobarbituric acid reactive substances, and the activities of antioxidant enzymes such as GST, GPX, SOD and CAT were examined in the blood and kidneys. Results: The acute toxicity experiments revealed that Syzygium cumini did not cause any obvious toxicity indications or mortality at a dosage of 300 mg kg-1, proving the safety of this extract with a broad therapeutic index. The results obtained showed that using aqueous Syzygium cumini seed extract for 21 days considerably (P &lt;0.05) increased the antioxidant enzyme activity for GST, GPx, SOD and CAT, while significantly (P &lt;0.01) decreasing the TBARS levels. Interpretation: Conclusively, the seed extract of Syzygium cumini might be a possible treatment for controlling hyperglycemic oxidative stress complications owing to its antioxidant properties. Key words: Albino rats, Antioxidant enzymes, Lipid peroxidation, Syzygium cumini, Seed extract

REDUCING INDICES OF OXIDATIVE STRESS CAUSED BY DIETARY AFLATOXINS WITH ANTIOXIDANTS AND VITAMIN K SUPPLEMENTATIONS

Aflatoxins are unavoidable toxic contaminants in animals’ feed. Nutrition-derived vitamins and mineral with antioxidant properties such as vitamins E, C and selenium can be used to counteract the Oxidative stress (OS) effects of aflatoxins on broiler chickens. Limited information exists on the combination and dosage of these antioxidants and vitamin K, that will be effective in counteracting OS effects of aflatoxins. Response of broiler chickens fed aflatoxin-contaminated diets to different combinations of Supplemental Dietary Antioxidants (SDA) and VK was investigated. One-day-old (n = 180) Arbor Acres broiler chick (unsexed) were randomly allotted into six treatment diets comprising Negative Control (NC), Basal Diet (BD), diet containing 270ppb aflatoxins and other BD’s containing vitamins: E (VE), C (VC), K (VK) and selenium (Se) at 200mg, 250mg, 3mg and 0.3mg/kg diet, respectively in four combinations: D1- (BD+VE+VC), D2- (BD+VE+VC+Se), D3 (BD+VE+VC+VK) and D4- (BD+VE+VC+VK+Se) Serum biochemical enzymes, reduced/oxidised glutathione (GSH/GSSG) and lipid peroxidation (LP) index (Malondialdehyde-MDA nmol/mL) were assayed. Experimental design was completely randomised and study lasted for 42 days. Data were analysed with ANOVA at α0.05. The SDA and VK significantly reduced LP activity by 30% reduction in MDA level from 128.29±31.16 (BD) to 42.00±10.40 (D4), compared to 10-fold increase in BD (128.29±31.16), against NC (12.41±10.56). Combinations of SDA and VK improved oxidative-stress index (GSH:GSSG) by 60% rise in D4 (2.19±0.92:1), as against 22.8% in BD (0.83±0.58:1), when compared to NC (3.64±1.44:1). Addition of supplemental dietary antioxidants and vitamin K reduced lipid peroxidation and oxidative stress effects of aflatoxins in broiler chickens.

Melatonin attenuates affective disorders and cognitive deficits induced by perinatal exposure to a glyphosate-based herbicide via antioxidant pathway in adult male and female rats.

The massive use of herbicides, particularly glyphosate-based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4mg/kg) from postnatal days 30-58. Our results show that GBH increases anxiety-like behavior levels in offspring, as well as depression-like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate-based pesticides. It will then be interesting to further our work to fully understand the sex-dependent effect of melatonin.

Changes in masseter muscle structure, membrane lipid peroxidation and Ca-ATPase activity as effects of different local anesthetics

Local anesthetics (LA) can cause undesired effects such as sustained contraction of skeletal muscles as a result of structural and functional changes. Proper skeletal muscle function is controlled by intracellular Ca2+ concentration and efficient energy (ATP) production, which is closely related to cell ultrastructure. Aim: The aim of this study was to identify the structural and functional changes caused by LAs. Materials and Method: Male Wistar rats weighing 200 to 250g were used (n:49). They were divided into seven groups. One group was not anesthetized or treated (Control). The other six groups underwent intramuscular (IM) anesthesia with xylazine 2% (0.05 ml) and ketamine 50 mg/ ml (0.1 ml/100g rat weight), and one of the following was applied to the masseter muscle (MM): no further treatment (Anesthetic Control group, CA); 0.1ml physiological saline solution (group SF); Carrageenin (group Carr) 1% as positive control group; prilocaine (group Pri), mepivacaine (group Mepi); or articaine (group Arti) 0.3M, IM. The animals were euthanized by cervical dislocation one hour after treatment. The effects of the different anesthetics on the MM were evaluated histologically and by electronic microscopy (EM). Ca-ATPase and membrane lipid peroxidation (LPX) were evaluated in muscle homogenates under the same conditions as those used to prepare the histological sections. Results: In general, structural damage and increased muscle contraction were observed in tissues treated with anesthetics. The most extreme values of Ca-ATPase activity and LPX were observed in the positive control group (carrageenin). Results were analyzed by one-way ANOVA for multiple comparisons and Tukey’s test (p &lt; 0.05). Conclusions: The results suggest that in the short term, local anesthetics affect the muscle function and are associated to structural changes.

Hesperidin Nanoformulation: A Potential Strategy for Reducing Doxorubicin-Induced Renal Damage via the Sirt-1/HIF1-α/VEGF/NF-κB Signaling Cascade.

Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavailability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques, such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels) was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were also considered. The results showed that pretreatment with Hes or Hes-NPs reduced doxorubicin's nephrotoxic effects, with Hes-NPs showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1; however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were considerably higher with Hes-NP than with Hes treatment. These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and anti-apoptotic effects.

Zinc oxide nanoparticles cause hepatotoxicity in rare minnow (Gobiocypris rarus) via ROS-mediated oxidative stress and apoptosis activation and inhibition of lipid peroxidation

Zinc oxide nanoparticles (ZnO NPs) measuring 30 ± 10 nm in diameter are utilized in various applications, including batteries, plastics, ceramics, cosmetics, flame retardants, and food. However, their potential impact and risk on aquatic ecosystems remain unclear. This study examined the hepatotoxic effects of dietary ZnO NPs in rare minnow. Three hundred rare minnows were fed diets containing 0 mg/kg, 20 mg/kg and 60 mg/kg of ZnO NPs for 60 days, with hepatotoxicity assessments at 15-day intervals. The histological data showed that ZnO NPs severely damage liver tissues, causing cytoplasmic vacuolization and irregular or missing nuclei. The treatment groups showed a significant rise in the liver injury index (P < 0.05). Moreover, there was a notable increase in zinc accumulation in the ZnO NPs groups compared to the control group (P < 0.05). ZnO NPs also reduced body weight and hepato-somatic index (HSI) in rare minnows. The enzyme activity results showed elevated levels of reactive oxygen species (ROS), total cholesterol (T-CHO), triglyceride (TG), acetyl Coa carboxylase (ACC), and fatty acid synthase (FAS) in the ZnO NPs fed groups, while total antioxidant capacity (T-AOC) and malondialdehyde (MDA) decreased. Further investigation found that accumulation of ZnO NPs in the liver tissues up-regulated the levels of genes related to antioxidant (mn-sod, cat and nf-κb), pro-apoptotic (bax) and lipogenesis (gpat3, dgat1a and dgat1b), while down-regulating genes associated with lipid catabolism (cpt1 and tpi1). These findings suggest that dietary ZnO NPs cause hepatotoxicity by inducing oxidative stress through ROS, triggering apoptosis, and inhibiting lipid peroxidation. The results indicate that ZnO NPs may pose a significant threat to aquatic animals and ecosystems.

Ameliorative Efficacy of &lt;i&gt;Moringa oleifera&lt;/i&gt; Lam. against the Sodium Fluoride Induced Nephrotoxicity in Wistar Rat

A study was conducted to evaluate the protective efficacy of a methanolic leaf extract of Moringa oleifera L. (MO) for the remediation of nephrotoxicity induced by exposure to a significant groundwater pollutant, fluoride. Wistar albino male rats weighing 150–200 g were divided into five groups, each containing five animals. The control group received normal drinking water, and Group I received sodium fluoride in drinking water (20 mg/l daily) for 90 days. Group II received M. oleifera extract (250 mg/l) for 90 days. Group III received sodium fluoride 20 mg/l along with a low dose of M. oleifera extract (250 mg/l) for 90 days, and Group IV received sodium fluoride 20 mg/l along with a high dose of M. oleifera extract (500 mg/l) for 90 days. After 90 days, the kidneys and blood samples were obtained to evaluate their histological characteristics and assess the levels of oxidative stress and various enzyme parameters. The current investigation showed that sodium fluoride has a notable impact on renal function by elevating levels of creatinine, Blood Urea Nitrogen (BUN), urea, as well as Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), and Alkaline Phosphatase (ALP) indicators. Further exposure resulted in a decrease in Superoxide Dismutase (SOD) and Catalase (CAT) levels, whereas Lipid Peroxidation (LPO) activity increased in kidney tissue. The histopathological examination of the kidney revealed glomerular enlargement, degenerative changes in Bowman’s capsule, and alterations in the tubular portion of the glomerulus. The study’s findings indicate that the administration of M. oleifera extract had a notable impact on the renal function and antioxidant status of rats subjected to sodium fluoride treatment. The administration of M. oleifera extract demonstrated a significant ability to mitigate the nephrotoxic effects induced by sodium fluoride in rats, mainly when both substances were concurrently administered. M. oleifera extract may also provide hepatoprotective effects by modifying membrane permeability and blocking enzymes from entering the serum.

The Effect of Trientine on AlCl3-Induced Cognitive Dysfunction and Biochemical Changes in the Hippocampus of Rats.

Cognitive impairments affect millions of people worldwide with an increasing prevalence. Research on their etiology and treatment is developing, nevertheless significant gaps remain. Trientine (TETA), as a copper chelator, has been shown to have beneficial effects in different human chronic diseases such as diabetic cardiomyopathy and neuropathy. Here, we examined the impact of TETA on AlCl3-induced neurocognitive dysfunctions and molecular changes in the hippocampus of rats.Thirty-six male Wistar rats (weighing 200-250 g) were randomly divided into four groups including control, TETA (100 mg/kg/day), AlCl3 (100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and received chemicals by gavage for 30 days. At the end of the treatment, the open field maze, elevated plus maze, novel object recognition memory test, and shuttle box test were done. Then after, brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity, oxidative stress markers, and inflammatory mediators were measured in the hippocampus.AlCl3 increased anxiety-like behaviors and impaired recognition and short-term memory. TETA was able to improve AlCl3-induced anxiety-like behaviors and short-term memory dysfunction. In the AlCl3-treated group, there was a significant increase in GSK-3β, oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF in the hippocampus. Co-administration of TETA was able to decrease lipid peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and increase BDNF in the hippocampus compared with AlCl3-treated rats.It can be concluded that TETA was able to improve neurobehavioral and neurocognitive functions by alleviating oxidative stress, inflammation, and pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.

Oxidative response to cadmium and lead accumulations in the tissues of blue swimming crabs Portunus pelagicus from the Trang Province coastline, Southern Thailand.

Metals have been reported to alter the oxidative status of both redox-active and redox-inactive metals accompanying oxidative stress induction. In aquatic ecosystems, metal contamination is regarded as serious pollutants and bioaccumulation, especially when aquatic seafood products are involved, which results in human risk. The blue swimming crab Portunus pelagicus is a highly popular crab species for consumption as seafood in Thailand. The meat parts and the hepatopancreas (HP) together with gonad are consumed and in high demand. Therefore, the present study aimed to investigate bioaccumulation of cadmium (Cd) and lead (Pb) along with tissue oxidative responses in P. pelagicus. Sixty-seven samples of P. pelagicus were obtained from small-scale fishers along the coastline of Trang Province. Bioaccumulation of Cd and Pb and oxidative response in gill, muscle, and HP + gonad were evaluated. Cadmium and Pb accumulation levels were highest in the HP and gonad, followed by the gill and then muscle, indicating that Cd and Pb have a high affinity to be concentrated in the HP and gonad. An organ-specific oxidative response to Cd and Pb accumulation was demonstrated in which Cd significantly activated superoxide dismutase (SOD) activity in the gills and muscle tissue, while Pb significantly activated the SOD activity only in the HP and gonad. Only Cd accumulation in gill tissue represented a significant activation of lipid peroxidation, as indicated by the malondialdehyde level. This study implied that P. pelagicus exhibits an "adaptive stage" in the oxidative response of tissue due to metal accumulation. Additionally, the data presented here further indicate that the consumption of only the meat parts and removal of the HP and gonad would reduce human exposure to metal toxicity.

ESSENTIAL OIL CONTENTS AND BIOLOGICAL ACTIVITIES OF THYMUS CANOVIRIDIS JALAS AND THYMUS SIPYLEUS BOISS.

Objective: Members of the Lamiaceae family are considered to be major sources of bioactive therapeutic agents. Many of them are important medicinal and aromatic plants used in traditional and modern medicine and in the food, cosmetic and pharmaceutical industries. The aim of this study was to investigate in detail the biological activities and chemical composition of the essential oils of Thymus canoviridis Jalas and Thymus sipyleus Boiss. species belonging to the genus Thymus, one of the most important genera of the Lamiaceae family. Material and Method: The essential oil content of the species was determined by GC-MS. Antioxidant activities of the essential oils were determined using lipid peroxidation, DPPH free radical, ABTS cation radical and CUPRAC methods. In addition, cytotoxic activities against breast cancer (MCF-7) and colon cancer (HT-29) cell lines and anticholinesterase (against AChE and BChE enzymes), urease, tyrosinase, elastase, collagenase and angiotensin converting enzyme inhibition activities were determined. Result and Discussion: When the essential oil composition of T. sipyleus was analyzed, the major compounds were 1,8-cineole (eucalyptol) (18.16%), camphor (15.08%) and endo-borneol (11.63%), while T. canoviridis was found to be rich in carvacrol (72.88%). T. canoviridis showed high antioxidant activity in lipid peroxidation (IC50: 45.72±0.12 μg/ml), ABTS (IC50: 6.12±0.03 μg/ml) and CUPRAC (IC50: 5.31±0.01 μg/ml) methods. The selectivities of T. canoviridis and T. sipyleus species against MCF-7 cell line were 4.39 and 6.81, respectively. In the enzyme inhibition studies, both Thymus species showed moderate inhibition activity against BChE enzyme (Inhibition%: 57.88±1.14, 39.21±0.89, respectively). In addition, T. sipyleus showed moderate inhibition of elastase enzyme (Inhibition%: 25.33±0.79). When the results are evaluated in general, it can be said that T. canoviridis essential oil with its rich carvacrol content and high cytotoxic and antioxidant activity can be preferred as a safer and natural option instead of synthetic preservatives in food, pharmaceutical and cosmetic industries to extend shelf life and ensure food safety.