Increased Malondialdehyde Levels Research Articles

2-Methylbutyric acid functions as a potential antifungal fumigant by inhibiting Botrytis cinerea and inducing resistance to gray mold in cherry tomatoes

Botrytis cinerea causes gray mold disease on postharvest fruit, resulting in serious economic losses. Fumigation with natural volatile organic compounds can replace artificially synthesized fungicides to control postharvest fungal decay of agricultural products. The antifungal effects and potential mechanisms of microbial volatile compound 2-methylbutyric acid (2-MBA) against B. cinerea were investigated in this study. Results showed that 2-MBA inhibited mycelial growth and spores germination, altered mycelial morphology and reduced metabolic vitality of B. cinerea. Moreover, 2-MBA induced oxidative damage by stimulating ROS accumulation, increasing malondialdehyde levels, and decreasing the ratio of reduced/oxidized glutathione. Further studies indicated that 2-MBA reduced mitochondrial membrane potential, interfered TCA cycle by decreasing succinate dehydrogenase activity and ATP content, ultimately leading to decreased mitochondrial activity. In addition, key genes involved in botrydial biosynthesis and mycelial growth were down-regulated. 2-MBA controlled postharvest gray mold by inducing resistance to B. cinerea in cherry tomatoes. Taken together, 2-MBA is an effective and promising fumigant to control gray mold caused by B. cinerea.

Adipose stem-cell-derived microvesicles ameliorate long-term bladder ischemia-induced bladder underactivity.

The mechanism for long-term hypoxia/ischemia induced bladder underactivity is uncertain. It requires an effectively therapeutic treatment. Therefore, we determined the pathophysiologic mechanisms of long-term bilateral partial iliac arterial occlusion (BPAO)-induced bladder underactivity and explored the therapeutic potential of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs) on BPAO-induced bladder dysfunction. The study included four groups: sham, BPAO, BPAO+ADSCs, and BPAO+ADSC-MVs. ADSCs or ADSC-MVs were isolated, characterized with specific CD markers and injected through the femoral artery to the rat bladders. Real-time laser speckle contrast imaging evaluated bladder microcirculation after BPAO. The transcystometrogram, pelvic nerve activity, bladder histology, immunohistochemistry, and lipid peroxidation assays were conducted after 4-week BPAO induction. The molecular mechanisms of bladder expression of purinergic P2X2/P2X3 and cholinergic M2/M3 receptors for regulating bladder contractility, nerve growth factor (NGF) for nerve injury repair, and collagen-1 for fibrosis were evaluated. Long-term BPAO significantly reduced bladder microcirculation, prolonged the intercontraction interval, decreased voiding volume, increased residual urine volume, lengthened phase 1 contraction, shortened phase 2 contraction, increased leukocytes and CD68 infiltration, increased malondialdehyde levels, and decreased levels of P2X3 and M3 receptors. ADSC-MVs were more efficient than ADSCs in improving BPAO induced parameters, recovering P2X3 and M3 receptors, increasing NGF expression, and decreasing collagen-1 expression in the bladder. ADSC-derived MVs were better than ADSCs to improve long-term BPAO-induced detrusor underactivity, bladder ischemia, and oxidative stress. ADSC-MVs through the therapeutic action of ameliorating inflammation, improving purinergic/cholinergic signaling and neuronal regeneration, and decreasing fibrosis improved BPAO-induced bladder underactivity.

Efficacy of lycopene in reducing malondialdehyde (MDA) levels due to Lipopolysaccharide (LPS) exposure in Mice (Mus musculus)

Objective: Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria and can trigger inflammatory and oxidative stress responses. This study aims to observe the efficacy of lycopene in reducing malondialdehyde (MDA) levels due to lipopolysaccharide (LPS) exposure in mice (Mus musculus). Method: This laboratory experimental study used 25 male mice aged 3 months with body weights of ± 25 g – 35 g, divided into five groups with five replicates each. K(-) was the control group: no LPS or lycopene was administered. K(+): received LPS 0.042 mg/kg without lycopene. P1: received LPS 0.042 mg/kg and lycopene 0.3 mg/kg. P2: received LPS 0.042 mg/kg and lycopene 0.6 mg/kg. P3: received LPS 0.042 mg/kg and lycopene 0.9 mg/kg. LPS was given on days 1 and 8 intraperitoneally, and lycopene was administered daily for 14 days. MDA levels were measured using the ELISA method, and data analysis was performed using ANOVA followed by Tukey's Test (p<0.05). Result: LPS exposure significantly increased MDA levels (p<0.05), and lycopene administration significantly reduced MDA levels (p<0.05) to normal levels similar to the control (-). Conclusion: LPS exposure significantly increased MDA levels, and lycopene administration was able to reduce MDA levels to normal limits.

Protective Role of Antioxidants in Cadmium-induced Reproductive Toxicity

Background: Studies on the role of oxidative stress in cadmium-induced reproductive toxicity have prompted numerous investigations into the use of antioxidants against reproductive toxicity. Natural compounds including curcumin and resveratrol have proven to be effective in mitigating oxidative damage. Ziziphus spina-christi (ZSC), is known for its abundance in antioxidant profile and has shown considerable protective effects against toxicity from heavy metals like cadmium. This current study seeks to uncover the mechanism behind which ZSC antioxidant properties protect against cadmium-induced reproductive toxicity. Methods: ZSC extract was prepared by harvesting, drying and processing the plant’s leaves. In-vivo experimental design was carried out, 24 rats were grouped in four groups: control group, ZSC treated group, Cadmium induced group and ZSC treated Cadmium induced group. To examine the oxidative stress, markers such as catalase, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were measured. Statistical analysis was performed using ANOVA, followed by Tukey’s multiple comparisons test to evaluate group differences. Result: Cadmium exposure led to a significantly decrease in catalase and SOD activities, alongside an increase in MDA levels, indicating an increased oxidative stress. Treatment with ZSC effectively restored these parameters towards normal levels, demonstrating its potent antioxidant activity. Interestingly, Females responded slightly better than males, suggesting a possible gender-specific effects. The observed reduction in cortisol levels further confirmed ZSC’s stress-reducing properties. These findings align with earlier studies on ZSC’s antioxidant and protective properties.

Insights into the antifungal activity and mechanisms of cinnamon components against Aspergillus flavus and Penicillium citrinum

Fungal spoilage of food and the excessive use of chemical disinfectants serves potential adverse effects on human health and the environment. Consequently, there is a growing interest in exploring natural alternatives, particularly plant-derived antimicrobial preservatives. Cinnamon extracts are known for their antifungal activity, but most research has focused on essential oils, rarely on other bioactive components. This study assessed the antifungal activity and underlying mechanisms of four components—trans-cinnamaldehyde, cis-2-methoxycinnamic acid, coumarin, and o-methoxycinnamaldehyde—extracted from Cinnamomum cassia Presl (cinnamon) against Aspergillus flavus and Penicillium citrinum. These cinnamon components can inhibit the two fungi strains at the minimum inhibitory concentration ranged from 0.30 to 8.55 mmol/L. These components can disrupt fungal cell membranes by enhancing relative electrical conductivity and cytoplasmic content leakage, reducing ergosterol content, and increasing malondialdehyde level. Additionally, they can affect fungal cell wall integrity, leading to the leakage of alkaline phosphatase and alterations in the contents of β-1,3-glucan and chitin. Moreover, the cinnamon components influenced the activities of malate dehydrogenase, succinate dehydrogenase, as well as adenosine triphosphate levels. The observed suppression of fungal contamination in A. flavus and P. citrinum suggests that these cinnamon components as potential natural antifungal agents.

Evaluation of Some Immunological and DNA Damage Parameters among Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) can cause permanent joint damage and disability through inflammation in the joints. Other organs, such as blood vessels, lungs, heart, eyes and skin may also get affected. This study aimed to evaluate the changes of some oxidative stress markers including oxidative DNA damage and the clinical outcomes that are associated with Iraqi rheumatoid arthritis patients. Commercial enzyme linked immunosorbent assay (ELISA) kits were applied to evaluate malondialdehyde (MDA), DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHDG), and glutathione peroxidase 3 (GPX3) levels in serum of 60 patients having RA with ages ranging between 20-70 years and 30 age-matched healthy controls. The results showed a significant increase in MDA levels in RA patients compared with the control group. Also, the levels of GPX3 decreased in RA patients with highly significant differences as compared with healthy control. Highly significant serum levels of oxidative DNA damage in RA patients were observed compared to the control group. Body Mass Index (BMI) results indicted significant differences between RA patients and healthy control. It can, therefore, be concluded that there is a potential role if malondialdehyde, oxidative DNA damage and GPX3 are used as biomarkers for progression of in patients with RA.

Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats.

An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10mg/kg) and CE (100mg/kg) were orally given. After 1h, 50mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.

Biomarker and adverse outcome pathway responses of Tubifex tubifex(sludge worm) exposed to environmentally-relevant levels of acenaphthene: insights from behavioral, physiological, and chemical structure-activity analyses.

Polycyclic aromatic hydrocarbons (PAHs), including acenaphthene, pose a significant threat to aquatic ecosystems by harming vital organisms such as benthic invertebrates. This study evaluated the impact of environmentally relevant concentrations of acenaphthene on Tubifex tubifex, focusing on sublethal acute toxicity and subchronic biomarker responses. Key biomarkers assessed included histopathological changes and the modulation of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and malondialdehyde (MDA). Additionally, the study examined structure-activity relationships and species sensitivity distribution (SSD). Concentrations exceeding the solubility threshold of acenaphthene (3.9 mg/L) triggered distinct, concentration-dependent behavioral responses in Tubifex tubifex, such as clumping, mucus secretion, and body wrinkling. Prolonged exposure exacerbated these behavioral dysfunctions, while subchronic exposure resulted in significant histopathological alterations, including epithelial hyperplasia, inflammation, edema, fibrosis, and degenerative changes. The edematic appearance of the body wall suggested a potential immune response to exposure. Furthermore, increased activities of CAT, SOD, and GST indicated oxidative stress in the worms. The study found a 1.5-fold increase in CAT and GST activity, a fivefold increase in SOD, and a striking 100-fold increase in MDA levels compared to controls, signifying an overwhelmed antioxidant defense system and potential cellular disruption. The SSD curve revealed hazard concentrations (HC50 and HC90), indicating that Tubifex tubifex exhibited lower sensitivity to acenaphthene compared to other taxa. In silico analysis and read-across models confirmed the potential of acenaphthene to induce significant oxidative stress upon exposure. The correlation between biomarker responses and structure-activity relationship analysis highlighted the aromatic nature of acenaphthene as a key factor in generating reactive metabolites, inhibiting antioxidant enzymes, and promoting redox cycling, ultimately contributing to adverse outcomes. These findings, coupled with behavioral responses and SSD curve inferences, underscore the importance of the solubility threshold of acenaphthene as a critical benchmark for evaluating its ecological impact in aquatic environments.

Genetic Adaptations of Soybean to Cold Stress Reveal Key Insights Through Transcriptomic Analysis.

Low temperatures greatly restrict the development, growth, and productivity of soybeans, with their effects differing across various cultivars. The present work investigated the transcriptome and physiological reactions of two soybean cultivars, namely "KD52" exhibiting cold tolerance and "DS17" displaying cold sensitivity, to cold stress across a precisely defined period. The soybean plants were subjected to cold treatment at 6 °C for durations of 0, 2, 4, and 8 h. A comparative physiological marker study revealed distinct reactions to cold stress in the two cultivars. The findings showed that increased malondialdehyde levels provided evidence of DS17's heightened vulnerability to lipid peroxidation and membrane degradation. In contrast, the KD52 cultivar exhibited increased activities of antioxidant enzymes, including peroxidase and superoxide dismutase, in response to cold exposure, suggesting a strong antioxidant defense system against oxidative stress. The transcriptomic analysis revealed dynamic responses, mapping 54,532 genes. Within this group, a total of 234 differentially expressed genes (DEGs) were found to be consistently changed at several time intervals, showing unique expression patterns across the two cultivars. Analysis of the association between these important DEGs and the physiological indicators revealed candidate genes that may be involved in controlling oxidative damage and antioxidant defenses. Some key genes showed a progressive rise in expression over time in both cultivars, with a more significant acceleration in KD52, and are probably involved in promoting adaptation processes during extended periods of cold exposure. The identification of improved defense mechanisms in KD52, together with the identification of crucial genes, offers great prospects for enhancing the cold stress resilience of soybean.

The Effect of Szigetvár Medicinal Water on HaCaT Cells Exposed to Dithranol.

(1) Introduction: Topical dithranol is still commonly used today as an effective treatment for psoriasis. Dithranol treatment is often supplemented with balneotherapy, which has been shown to increase effectiveness and reduce side effects. The inorganic salts (sulfhide, selenium, zinc) are usually thought to be responsible for the effect. The antioxidant effect of the waters is thought to be behind the therapeutic effect, for which inorganic substances (sulfides, selenium, zinc) are thought to be responsible. The organic matter content of medicinal waters is also particularly important, as humic acids, which are often found in medicinal waters, have antioxidant effects. (2) Methods: In this short-term experiment, we aimed to test the possible protective effect of Szigetvár medicinal water and its organic matter isolate on HaCaT cells exposed to dithranol. Malondialdehyde levels were measured, and RT-qPCR was used to investigate the gene expression of selected cytokines relevant in the oxidative stress response (IL-6, IL-8, TNF-α, GM-CSF) and the expression of microRNA-21. (3) Results: Szigetvár medicinal water and the organic isolate prevented the increase in malondialdehyde levels caused by dithranol treatment. The cytokine gene expressions elevated by dithranol exposure were reduced by the treatment. (4) Conclusions: Szigetvár medicinal water and organic substances alone may have a protective effect on patients' healthy skin surfaces against dithranol damage. We also demonstrated that the organic compounds are also responsible for the protective effect.

Effects of Gingko Biloba Extract and L-Ascorbic Acid on Some Hematological, Biochemical, and Hepatic-Architectural Alterations in Mercury Chloride Intoxicated Adult Wistar Rat.

The study investigated the effects of Ginkgo biloba and Ascorbic acid (A.A) on mercury chloride (HgCl2) toxicity in Wistar rats. Forty-two adult Wistar rats were randomly divided into seven groups (n=6). Group I served as control. Groups II–VII received 5 mg/kg of HgCl2. Groups III and IV received 100 mg/kg and 500 mg/kg of A.A respectively, while groups V and VI daily received 100 mg/kg and 500 mg/kg of EGB761 respectively. Group VII received 100 mg/kg of A.A and EGB761. All administration were done orally, once daily for 21 days. Mercury exposure caused significant (p&lt;0.05) decreases in RBC (3.62.00±0.75), hemoglobin (8.67±0.14), and PCV (32.93±0.47) in group II when compared to the control group, while significantly (p&lt;0.05) increasing white blood cell count (18.57±1.51). Liver function tests significantly (p&lt;0.05) increased Alanine transaminase (1.38±1.51), Aspartate Transaminase (10.11±4.21), and Alkaline Phosphatase (1.89±0.51) in group II when compared to Control. Biochemical analysis revealed a significant (p&lt;0.05) increase in malondialdehyde levels and a significant (P&lt;0.05) decrease in superoxide dismutase (3.86 ± 0.69), glutathione (10.08 ± 2.13), and catalase (3.65 ± 0.2) levels in group II. However, treatment with ascorbic acid and EGB761 significantly (P&lt;0.05) increased in Groups IV (6.15 ± 0.38); VI (6.28 ± 0.40), and VII (6.19 ± 0.41), SOD levels in Groups IV (6.15 ± 0.38); VI (6.28 ± 0.40) and VII (6.19 ± 0.41) and GSH level when compared to the HgCl2 group. Histological examination showed moderate hepatocyte necrosis in group II, while treatment with EGB761 and A.A showed moderate healing, binucleate nuclei, and a slight decrease of distorted sinusoids and normalization of liver structure. The study concludes that EGB761 and A.A have hepatoprotective effects on mercury-induced hepatotoxicity in a dose-dependent manner. The findings suggest that these antioxidants may be useful in mitigating the harmful effects of mercury exposure on the liver.

Protective Effects of Lactobacillus Strains Against Oxidative Stress and Immune Suppression in Mice Receiving Aflatoxin-Contaminated Diet.

Mycotoxins like aflatoxins pose a significant threat to the health of both people and animals because of their deadly effects. This study aimed to investigate the potential of Lactobacillus strains in reducing the toxicity caused by aflatoxins in mice receiving a diet contaminated with aflatoxins. The mice were split up into various treatment groups, including a control group, an aflatoxin-treated group, and groups treated with the aflatoxin-contaminated diet along with Lactobacillus strains. Various parameters, including liver enzymes, blood parameters, malondialdehyde (MDA) levels, morphometric analysis of ileum, and gene expression, were analyzed to assess the effectiveness of the Lactobacillus strains in mitigating aflatoxins toxicity. Results showed that mice in the aflatoxin-treated group had increased MDA levels, indicating oxidative stress. Alternatively, the Lactobacillus cocktail treatment group showed a decreasing trend in MDA levels, suggesting a reduction in lipid peroxidation. The morphometric analysis of ileum tissue demonstrated that the Lactobacillus-treated group exhibited improved structural integrity compared to the aflatoxin-treated group. Additionally, gene expression analysis revealed that the Lactobacillus treatment attenuated the downregulation of SOD gene expression and mitigated the upregulation of iNOS gene expression induced by aflatoxins. These findings suggest that Lactobacillus strains have the potential to reduce aflatoxin-induced toxicity by alleviating oxidative stress, preserving intestinal tissue integrity, and modulating gene expression associated with antioxidant defense and inflammation. This study provides evidence for the beneficial effects of Lactobacillus strains in reducing aflatoxin toxicity in mice. The findings obtained may contribute to the development of preventive or therapeutic strategies against mycotoxin-induced toxicity.

β-carotene protects against α-amanitin nephrotoxicity via modulation of oxidative, autophagic, nitric oxide signaling, and polyol pathways in rat kidneys

Alpha-amanitin (α-AMA), a toxic component of Amanita phalloides, causes severe hepato- and nephrotoxicity. This study investigated the protective effects of βeta-carotene (βC) against α-AMA-induced kidney damage in rats. Thirty-two male Sprague-Dawley rats were divided into four groups: Control, βC (50 mg/kg/day), α-AMA (3 mg/kg), and βC+α-AMA. βC was administered orally for 7 days before α-AMA injection. Renal function, oxidative stress markers, histopathological changes, and enzyme activities were evaluated 48 h post-α-AMA administration. α-AMA significantly increased serum creatinine and urea levels, decreased glutathione and catalase activity, and increased malondialdehyde levels (P < 0.001). βC pretreatment attenuated these changes (P < 0.05). Histopathological examination revealed reduced tubular degeneration in the βC+α-AMA group (P < 0.001). Immunohistochemical analysis showed increased LC3B and Beclin-1 expression in α-AMA-treated rats, indicating enhanced autophagy, partially reversed by βC. Additionally, α-AMA reduced nitric oxide synthase (NOS) activity and increased aldose reductase (AR) activity, both normalized by βC pretreatment (P < 0.01). βC demonstrates protective effects against α-AMA-induced nephrotoxicity through antioxidant action, modulation of autophagy, and regulation of NOS and AR pathways, suggesting its potential as a therapeutic agent in α-AMA poisoning.

Evaluation of Antioxidant Effects of Coenzyme Q10 against Hyperglycemia-Mediated Oxidative Stress by Focusing on Nrf2/Keap1/HO-1 Signaling Pathway in the Liver of Diabetic Rats.

Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10's antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway. This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD's or Tukey's post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant. The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNA expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group. The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway.

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats: Focus on oxidative and sex hormone receptors mechanisms

Objective: To investigate the potential of N-acetylcysteine (NAC) and zinc sulphate (ZnSO4) in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate (DEHP) in rats and to understand the underlying mechanisms, specifically oxidative stress and sex hormone receptor activity. Methods: Thirty-five male Wistar rats were randomly divided into five equal groups (n=7 per group). Group 1 was administered 0.5 mL of distilled water and served as the control group. Group 2 was given only DEHP (750 mg/kg/day), while group 3, 4 and 5 were given DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day), DEHP (750 mg/kg/day) plus ZnSO4 (0.5 mg/kg/day), and DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day) as well as ZnSO4 (0.5 mg/kg/day), respectively. All treatments lasted for 21 days. Samples were obtained after the rats were sacrificed, and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay. The amount of androgen receptors in the testicles was determined by immunohistochemistry, and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies. Results: DEHP decreased reproductive hormones, testicular antioxidant enzymes, increased malondialdehyde levels, and negatively impacted histology of the pituitary and testes. NAC or ZnSO4 treatment showed a marked improvement in testicular antioxidant status and hormone levels, as well as a positive effect on the histology of the pituitary and testes. The combination of both treatments appeared to be more effective. The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling, which can further result in dysfunction of hormones related to androgen. However, NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors, as well as gonadotropin-releasing hormone receptors, when compared to DEHP. Conclusions: The possibility that NAC and ZnSO4 could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

The effect of norepinephrine on ovarian dysfunction by mediating ferroptosis in mice model.

Studies have shown that stress is associated with ovarian dysfunction. Norepinephrine (NE), a classic stress hormone involved in the stress response, is less recognized for its role in ovarian function. In this study, an NE-treated mouse model is induced by intraperitoneal injection of NE for 4 weeks. Compared with normal control mice, NE-treated mice show disturbances in the estrous cycle, decreased levels of anti-Mullerian hormone (AMH) and estradiol (E2), and increased level of follicle-stimulating hormone (FSH). Additionally, the numbers of primordial follicles, primary follicles, secondary follicles, and antral follicles are decreased, whereas the number of atretic follicles is increased in NE-treated mice, indicating NE-induced ovarian dysfunction. RNA sequencing further reveals that genes associated with ferroptosis are significantly enriched in NE-treated ovarian tissues. Concurrently, the levels of reactive oxygen species (ROS), ferrous ions, and malondialdehyde (MDA) are increased, whereas the expression level of glutathione peroxidase 4 (GPX4) is decreased. To elucidate the mechanism of NE-induced ferroptosis in ovaries and the potential reversal by Coenzyme Q10 (CoQ10), an antioxidant, we conduct both in vitro and in vivo experiments. In vitro, the granulosa cell line KGN, when treated with NE, shows decreased cell viability, reduced expression of GPX4, elevated levels of ferrous ion and ROS, and increased MDA level. However, these NE-induced changes are reversed by the addition of CoQ10. Compared with the NE group, the NE-treated mice supplemented with CoQ10 present increased GPX4 level and decreased iron, ROS, and MDA levels. Moreover, the differential expression of genes associated with ferroptosis induced by NE is ameliorated by CoQ10 in NE-treated mice. Additionally, CoQ10 improves ovarian function, as evidenced by increased ovarian weight, more regular estrous cycles, and an increase in follicles at various stages of growth in NE-treated mice. In conclusion, NE induces ovarian dysfunction by triggering ferroptosis in ovarian tissues, and CoQ10 represents a promising approach for protecting reproductive function by inhibiting ferroptosis.

Serum Malondialdehyde Level as a Predictor of Failure of Weaning from Mechanical Ventilation in the Neonatal Intensive Care Units

Abstract Background Mechanical ventilation is a lifesaving treatment used in critical neonatal patients. It is indicated when the patient's spontaneous ventilation is insufficient to sustain life. Mechanical ventilation expedites and facilitates gas exchange, oxygenation, and CO2 removal. Despite advances in non-invasive ventilatory support methods, intubation and mechanical ventilation are still common treatments in NICUs. Objective To evaluate whether or not serum malondialdehyde (MDA), as a marker for oxidative stress, could be used as a mean to predict the neonatal weaning failure from mechanical ventilation. Methods This is a prospective cohort study included 31 full and preterm neonates on invasive mechanical ventilation ≥72 hours was conducted in Neonatal Intensive Care Unit Ain Shams University, children Hospital, after approval of the Research Ethics Committee Faculty of Medicine Ain Shams University from 1/3/2022 to 1/11/2022. Inclusion criteria of enrolled neonate includes full term (≥37 weeks) and preterm (33-36 weeks) neonates within their 28 days of life, neonates on invasive mechanical ventilation ≥ 72 hours and neonates ready to be weaned according to weaning Protocol. Results Serum level of MDA after half and 72 hours in weaning failure neonates (627 and 2000 ng/ml) compared to serum level of MDA pre-Spontaneous breathing test (SBT) (325.9 ng/ml) with p-value= 0.000. Serum level of MDA in weaning success patient pre-SBT, after half and 72 hours (163,124.2 and 63.9 ng/ml) compared to weaning failure patient (325.9,672 and 2000ng/ml) with p- value= 0.000. Our study revealed highly significant increase in serum level of MDA in weaning failure patients after half and 72 hours of extubation with p-value = 0.000. Pre extubation serum MDA level to Predict weaning failure was &amp;gt;223 ng /ml. Conclusion This study demonstrated significant increase in the level of pre-extubation serum MDA in the weaning failure group than weaning success. Serum MDA could be used as mean to predict weaning failure from mechanical ventilation.

Protective Effect of Chlorogenic Acid Against Testicular Damage Induced By Glyphosate Isopropilamine in Rats

The aim of this subchronic toxicity study was to determine the prophylactic effect of chlorogenic acid (CGA) on the histopathologic-histologic changes and oxidative stress induced by Glyphosate isopropylamine (GLF-ISO) in testicular tissues. A sum of 42 male Wistar rats were divided into six equal groups, each containing 7 rats. For pretreatment, rats were given CGA at doses of 12.5, 25 and 50 mg/kg (po) and GLF-ISO at 787.85 mg/kg (po) for 7 weeks. GLF-ISO significantly increased malondialdehyde levels while decreasing SOD and CAT activities and GSH levels in testicular tissues. On the contrary, these parameters were improved in CGA-treated groups. Furthermore, CGA ameliorated the histopathological and histological changes in testicular tissues induced by GLF-ISO in a dose-dependent manner. The results indicate that testicular damage caused by GLF-ISO can potentially be prevented or managed by CGA.

The Effect of Sub-Acute Inhalation Exposure to Polyethylene and Polyvinyl Chloride Micro-Nano Plastics on the Superoxide Dismutase (SOD) Level and Malondialdehyde (MDA) Level in Rat Ovary

Plastic is a synthetic or semi-synthetic organic polymer that is widely used in daily life and in industrial production. Microplastics are widespread contaminants and can enter the human body through the consumption of foods containing microplastics, inhalation of microplastics in the air, and skin contact with microplastic particles present in products. Microplastics can enter the ovaries as foreign bodies and can cause inflammation, oxidative stress, and even ovarian granulosa cell death. Polyethylene plastic shards generally have a higher ability to absorb environmental toxins than other types of plastic. Polyvinyl chloride (PVC) is one of the oldest thermoplastic polymers that is often used as water pipes. PVC has carcinogenic monomers and some harmful additives. This study aims to determine the effect of subacute exposure to micro-nanoplastics per inhalation on SOD and MDA levels in rat ovaries. The research method used is a true experimental design with a Randomize Post Test Only Group Design research design. This study used the ovarian organs of female white rats that had been exposed to PVC and PE for 28 days. The number of samples used in this study amounted to 18 female rats. Subacute exposure to micro-nanoplastics per inhalation can lower SOD levels and significantly increase MDA levels in rat ovaries. This study is expected to provide knowledge and an overview for future research on the mechanism of toxicity of micro-nanoplastic exposure that has an impact on female infertility through free radicals in the ovaries.

Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia

BackgroundHyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.MethodsThe acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.ResultsLevels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.ConclusionsBiomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.