Administration Of Antioxidants Research Articles

Enteric neuroprotection-A matter of balancing redox potentials, limiting inflammation, and boosting resilience.

The enteric nervous system (ENS) orchestrates intricate and autonomous functions throughout the gastrointestinal (GI) tract. Disruptions in ENS function are associated GI disorders. This mini review focuses on the past decade's research, utilizing rodent models, with an emphasis on protecting enteric neurons from loss. The review specifically looks at efforts to reduce oxidative stress, limit inflammation, and enhance neuronal resilience. Protective interventions including administration of antioxidants and compounds targeting cellular redox buffer systems, are evaluated for their effectiveness in preventing loss of enteric neurons in the ischemia-reperfusion model and streptozotocin-induced diabetes model. Interventions such as engrafting mesenchymal stem cells and targeting inflammatory signaling pathways in enteric neurons and glial cells are evaluated in inflammatory bowel disease models including the Winnie mouse, DSS-, and DNBS/TNBS-induced colitis models. The review also touches upon neuronal resilience, particularly in the context of Parkinson's disease models. Including estrogen's neuroprotective role, and the influence of metal ions on enteric neuronal protection. Understanding the dynamic interplay within the ENS and its role in disease pathogenesis holds promise for developing targeted therapies to effectively manage and treat various GI ailments.

Tebuconazole Induces Mouse Fetal Testes Damage via ROS Generation in an Organ Culture Method.

The fungicide tebuconazole (TEB) poses risks to human and animal health via various exposure routes. It induces toxicity in multiple organs and disrupts reproductive health by affecting steroid hormone synthesis and fetal development. In this study, we investigated the impact of TEB on fetal testes using in vitro models, focusing on germ, Sertoli, and Leydig cells, and explored the mechanisms underlying cellular damage. The results revealed significant damage to germ cells and disruption of Leydig cell development. TEB exposure led to a decrease in germ cell numbers, as indicated by histological and immunostaining analyses. TEB induced the up- and down-regulation of the expression of fetal and adult Leydig cell markers, respectively. Additionally, TEB-treated fetal testes exhibited increased expression of oxidative-stress-related genes and proteins. However, co-treatment with the antioxidant N-acetylcysteine mitigated TEB-induced germ cell damage and prevented abnormal Leydig cell development. These findings suggest that administration of antioxidants can prevent the intratesticular damage typically caused by TEB exposure.

Understanding complex effects on clinical outcomes and biomarker activities of food supplementation in heavy smokers: an approach using bayesian networks

BACKGROUND: Antioxidant administration can significantly alleviate smoking-mediated oxidative stress. In our previous research, using a concentrated mixed juice powder led to significant reduction in oxidative status markers and improved lung function among smokers. OBJECTIVE: To compare the effectiveness of different antioxidant formulations of the retail product Juice Plus+® on oxidative status and lung function in healthy smokers via a a Bayesian Network (BN) analysis. METHODS: At baseline and after 3 months’ supplementation, pulmonary function, cardiovascular risk factors, and oxidative status were assessed in 101 smokers, randomized into three groups: placebo (P), fruit/vegetable (FV), and fruit/vegetable/berry (FVB) group. BN analysis was performed via Monte Carlo simulations. Statistical significance was assigned as p < 0.05. RESULTS: No significant interaction was observed in P (network score –101.4, p = ns), whereas overall fit significantly improved in both FV (network score –185.7, p = 0.01) and FVB (–293.7, p = 0.003). Moreover, P group’s respiratory parameters appeared unrelated to the biochemical structure, whereas those of the FV and, to a greater extent, FVB groups were definitely related to it CONCLUSIONS: BN analysis demonstrated that the FV and FVB formulations contain nutraceutical compounds capable of synergistically acting and improving antioxidant modulation and respiratory function in smoking subjects

Isoniazid-Induced Cerebellitis in a Chronic Kidney Disease Patient

Abstract The bacterial disease tuberculosis (TB), when it affects organs of the body other than the lungs, is called extrapulmonary TB. The treatment regimen includes the drugs isoniazid, rifampicin, pyrazinamide, and ethambutol, of which isoniazid is known to be the most active drug. Adverse drug reactions commonly include immunological as well as drug toxicity effects, with the latter being particularly important in renally impaired patients because of high risk of drug accumulation. Cerebellitis, which is an inflammatory condition that results in cerebellar dysfunction, is a rare complication of isoniazid use. Diagnosis is made after excluding all other possibilities. In the case described here, the extrapulmonary TB patient was a known case of chronic kidney disease (G4). He presented with slurred speech and sedation; magnetic resonance imaging scan showed bilateral fluid-attenuated inversion recovery hyperintensities in the dentate nuclei, indicative of cerebellitis. Dramatic improvement was seen upon replacing Isoniazid with levofloxacin and administration of antioxidants and pyridoxine supplements, which confirmed the diagnosis of isoniazid-induced cerebellitis.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Effects of antioxidant supplementation for polycystic ovary syndrome

Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment. A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality. Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.

Erratum in the article “Possible prospects for the combined administration of antidepressants and antioxidants in neurological patients”

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Effects of cancer-induced cachexia and administration of l-glutathione on the intestinal mucosa in rat

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% l-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% l-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% l-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by l-glutathione. On the other hand, l-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

Breath of Danger: Unveiling PM2.5's Stealthy Impact on Cancer Risks.

This article explores the intricate relationship between airborne particulate matter (PM), specifically PM2.5, and its profound impact on human health, emphasising the heightened risks of cancer. Examining the composition and characteristics of PM2.5, such as particle size and surface area, reveals its ability to induce inflammatory injury and oxidative damage. The carcinogenic potential extends beyond respiratory implications, affecting various organs, including the digestive tract, breast, and prostate. In addition to the genotoxic effects of PM2.5, attached polycyclic aromatic hydrocarbons are recognized to be endocrine-disrupting chemicals with specific implications for breast and prostate cancer. Long-term exposure to PM2.5 is associated with increased cancer mortality, with specific risks identified for different cancer types. The linear correlation between cancer risk and PM2.5 concentration calls for a re-evaluation of permissible emission levels. The article concludes by proposing specific mitigating strategies for individuals exposed to elevated PM2.5. It suggests antioxidant-rich diets and supplements, and exploring inhalation-based antioxidant administration as potential protective measures.

Oxidative Stress Status in Heat Shock Sheep Controlled Shearing and Ascorbyl Palmitate Administration

Indonesia has very hot temperatures and high humidity, making it unfavorable for sheep whose covered with thick fur. Shearing enlarges and accelerates heat dissipation from the sheep's body, giving antioxidants that help reduce the negative effects of excessive free radical production. Ascorbic acid is an antioxidant but is easily decomposed when it enters the digestive system of ruminants. Ascorbyl palmitate (AP) is ascorbic acid in the form of an ester which is insoluble in water. The aim of this study was to analyze the effect of shearing and administration of AP antioxidants on oxidative stress conditions in Padjadjaran sheep subjected to heat shock. The shaving treatment consisted of not shaving (s0) and shearing (s1),and the treatment of giving the antioxidant ascorbyl palmitate consisted of not being given (a0) and being given (a1). Sheep were subjected to shearing, their hair was trimmed until ± 10 mm in length was left, and sheep as object of study were treated with ascorbyl palmitate at a dose of 400 mg head-1 day-1. The combination treatment was not shaved – not given the antioxidant ascorbyl palmitate (s0a0), only shaved (s1a0), only given the antioxidant ascorbyl palmitate (s0a1), and sheared – given the antioxidant ascorbyl palmitate (s1a1). Heat shock is given by exposing the sheep to the sun. The oxidative stress observed and analyzed was the profile of endogenous antioxidants consisting of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The results showed that the combination of shearing and Ascorbyl Palmitate had a significant effect (p<0.05) on the levels of SOD, CAT and GSH-Px in Padjadjaran sheep receiving heat stress. The conclusion from this study, the shearing treatment and the administration of Ascorbyl palmitate, both independently and in combination, had a beneficial effect on Padjadjaran sheep.

Ameliorative effect of Ononis natrix against chronic lead poisoning in mice: neurobehavioral, biochemical, and histological study.

Lead (Pb) is one of the most common heavy metals with toxicological effects on many tissues in humans as well as animals. In order to counteract the toxic effects of this metal, the administration of synthetic or natural antioxidants is thus required. The aim of this study was to examine the beneficial effect of the aqueous extract of Ononis natrix (AEON) against lead acetate-induced damage from a behavioral, biochemical, and histological point of view. Forty-eight male mice were divided into four equal groups: Ctr (control); Pb (lead acetate 1g/l); Pb + On 100 mg/kg (lead acetate 1 g/l + AEON 100 mg/kg); Pb + On 500 mg/kg (lead acetate 1 g/l + AEON 500 mg/kg). AEON was administered orally from day 21 after the start of lead exposure up to the end of the experiment. The results revealed that lead induced behavioral disorders, increased serum levels of liver markers (AST, ALT, and bilirubin), as well as kidney markers (urea and creatinine). At the same time, levels of thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) increased significantly. Moreover, Pb caused structural changes in the liver and kidneys of Pb-exposed mice. However, AEON administration significantly improved all lead-induced brain, liver, and kidney dysfunctions. Our results suggest that AEON could be a source of molecules with therapeutic potential against brain, liver, and kidney abnormalities caused by lead exposure.

Optimization of Laser-Based Method to Conduct Skin Ablation in Zebrafish and Development of Deep Learning-Based Method for Skin Wound-Size Measurement

Skin plays an important role as a defense mechanism against environmental pathogens in organisms such as humans or animals. Once the skin integrity is disturbed by a wound, pathogens can penetrate easily into a deeper part of the body to induce disease. By this means, it is important for the skin to regenerate quickly upon injury to regain its protective barrier function. Traditionally, scientists use rodents or mammals as experimental animals to study skin wound healing. However, due to concerns about animal welfare and increasing costs of laboratory animals, such as rodents, scientists have considered alternative methods of implementing replace, reduce, and refine (3Rs) in experimentation. Moreover, several previous studies on skin wound healing in fish used relatively expensive medical-grade lasers with a low calculation efficiency of the wound area, which led to human judgment errors. Thus, this study aimed to develop a new alternative model for skin wound healing by utilizing zebrafish together with a new rapid and efficient method as an alternative in investigating skin wound healing. First, in order to fulfill the 3Rs concept, the pain in the tested zebrafish was evaluated by using a 3D locomotion assay. Afterward, the obtained behavior data were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple comparisons tests; later, 3 watts was chosen as the power for the laser, since the wound caused by the laser at this power did not significantly alter zebrafish swimming behaviors. Furthermore, we also optimized the experimental conditions of zebrafish skin wound healing using a laser engraving machine, which can create skin wounds with a high reproducibility in size and depth. The wound closure of the tested zebrafish was then analyzed by using a two-way ANOVA, and presented in 25%, 50%, and 75% of wound-closure percentages. After imparting wounds to the skin of the zebrafish, wound images were collected and used for deep-learning training by convolutional neural networks (CNNs), either the Mask-RCNN or U-Net, so that the computer could calculate the area of the skin wounds in an automatic manner. Using ImageJ manual counting as a gold standard, we found that the U-Net performance was better than the Mask RCNN for zebrafish skin wound judgment. For proof-of-concept validation, a U-Net trained model was applied to study and determine the effect of different temperatures and the administration of antioxidants on the skin wound-healing kinetics. Results showed a significant positive correlation between the speed of wound closure and the exposure to different temperatures and administration of antioxidants. Taken together, the laser-based skin ablation and deep learning-based wound-size measurement methods reported in this study provide a faster, reliable, and reduced suffering protocol to conduct skin wound healing in zebrafish for the first time.

Use of Ozone Therapy and Thymoquinone in the Prevention of Formaldehyde Toxicity by Inhalation: An Experimental Study.

The study determined the damage caused by formaldehyde (FA) exposure in blood and liver samples using biochemical markers. Histopathological analysis was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method and measurement of CD68 cell density. To what extent the antioxidant molecules thymoquinone (TQ) and ozone (O3) reversed the damage caused by FA exposure was investigated, both when used alone and combined. Fifty-six Sprague-Dawley male rats of eight to ten weeks of age were used in the experiment. The rats were divided into eight groups, with seven rats in each group: the untreated control group, the group treated with TQ (10 mg/kg/day), the group treated with O3 (150 μg/kg/day), the group treated with TQ+O3, the group exposed to FA (10 ppm 8 h/day), the group receiving FA+TQ, the group receiving FA+O3, and the group receiving FA+TQ+O3.Serum aspartate transaminase (AST), alanine transaminase (ALT), total antioxidant (TAS, U/mL), and total oxidant (TOS, nmol/mL) levels were analyzed. TAS and TOS levels, CD68 cell density, and apoptotic cells were determined in liver tissues. FA exposure caused an increase in serum AST and ALT levels of (p<0.05) experimental animals, a decrease in TAS levels in serum (p=0.03) and liver (p>0.05) and an increase in TOS levels (p>0.05), TUNEL positivity (p<0.001), and CD68 cell density (p=0.004). Administration of TQ and O3as antioxidants significantlyreversed biochemical and histopathological alterations in the serum and liver. TQ and ozone therapy suppressed oxidative stress caused by FA exposure and reversed the emerging histopathological deteriorations. Ozone therapy did not suppress the effects of TQ. Therefore, ozone therapy can be given as a supportive therapy along with the main therapeutic agents. We think TQ and ozone therapy may be useful to protect individuals exposed to FA.

In vivo and in vitro effects of crocetin and its amide derivative on acrylamide-induced neurotoxicity.

Acrylamide (ACR) is a neurotoxic agent whose damage could be attenuated by antioxidants administration. Crocetin is a saffron-derived antioxidant that has neuroprotective effects. This study evaluates the protective effects of trans-sodium crocetinate (TSC) and its water-soluble derivative, Bis-N-(N-methylpyprazinyl) crocetinate (BMPC) against ACR neurotoxicity. PC12 cells were treated with TSC and BMPC (1.95, 3.9, 7.81, 15.62, 31.25, 62.5, 125, 250, 500, and 1000 μM) for 24 hr. ACR was then added at a concentration of 6.5 mM (IC50), and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide. In the in vivo study, male Wistar rats were treated with ACR (50 mg/kg, intraperitoneal (i.p.)) for 11 days alone or in combination with TSC and BMPC (2.5, 5, and 10 mg/kg, i.p.) or vitamin E (200 IU/kg, i.p.). Motor impairments were then evaluated. The cerebral cortex of sacrificed rats was taken for the malondialdehyde (MDA) and glutathione (GSH) levels measurement. In vitro studies showed that TSC at a concentration of 7.81 μM and BMPC at concentrations of 3.9, 7.81, and 15.62 μM exhibited the lowest toxicity in acrylamide administration. In the in vivo study, pretreatment with 2.5, 5, and 10 mg/kg of TSC ameliorated behavioral impairments, but BMPC could not attenuate them. GSH and MDA were improved by 2.5, 5, and 10 mg/kg TSC and 2.5 mg/kg BMPC. TSC and BMPC administration improved behavioral index and oxidative stress injuries in Wistar rats exposed to ACR through MDA reduction and GSH content enhancement in the cerebral cortex.

Autoxidation interference assay to evaluate the protection against lipid oxidation of antioxidant administration: Comparison of the efficiency of progressive release or total administration

Lipid oxidation is a cause of food spoilage, and antioxidants are used to retard it, but the timing of administration is important for this effect. The research aims to evaluate the protective efficiency against oxidative deterioration through the prolonged or complete addition of antioxidants without retention in the matrix. For this purpose, three modes of administration of the synthetic antioxidant BHT and oregano essential oil were evaluated: 100, 50, and 25 in which 100 % was incorporated at the beginning, 50 % in two aliquots, and 25 % in 4 aliquots. After adding the aliquots, all treatments reached 0.02 w/w of antioxidant in oil. An accelerated oxidation study was performed at 60 °C for 12 days, and chemical indicators (Peroxide and Conjugated Dienes value) along with volatiles (2-Heptenal and 2,4-Decadienal EE) were assessed. The order of protection shows that the initial addition of antioxidants yielded the highest efficiency.

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota’s influence

The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.

The role of Reactive Oxygen Species (ROS) in the Nandrolone-Decanoate-induced liver fibrosis

To determine the role of reactive oxygen species (ROS) and its relationship with tumor necrosis factor-alpha (TNF-alpha) during the process of developing liver fibrosis induced by Nandrolone Decanoate, 36 adult male Wistar rats are divided into 3 groups. Except for the control group, the other 2 experimental groups are injected with nandrolone decanoate (3.5 mg/kg/5 times/IM/week) for 4 weeks. After 4 weeks of injection, one experimental group (A) is decapitated. Samples from livers and plasma are obtained to conduct histopathological section, TNF-alpha ELISA, and EPR for ROS level. Then along with the same dosage of nandrolone decanoate, raxofelast (15mg/kg/day) is administrated orally to the experimental group (B) for another 4 weeks. The result of the histopathology section, ELISA, and EPR tests of group A and group B were compared. The degree of liver fibrosis, reactive oxygen species amount, and TNF-alpha level before and after the administration of antioxidants indicate the role of ROS in the development of TNF-alpha-mediated liver fibrosis. Another purpose of this experiment is to discuss the potential of antioxidants in the treatment of steroid-induced liver fibrosis.

Effects of antioxidant treatment on cell differentiation in rabbit embryos

The antioxidant coenzyme Q10 can influence the expression of genes involved in apoptosis and energy metabolism of oocytes and quercetin can improve oocyte maturation and early embryonic development. In this study, the gene expression of GATA6 and NANOG in rabbit embryos was assessed using the qRT-PCR reaction. The groups were: group A- control group (no treatment added), group B (hormonal treatment of superovulation, which included the administration of PMSG and hCG), group C (administration of quercitin) and group D (administration of Coenzyme Q10). Our results show that the expression of the two genes was different depending on both the stage of embryonic development and the treatment administered. The highest values of gene expression for GATA6 and NANOG were obtained in groups 2, 4, 7, 8 and 9, corresponding to morula and blastocyst stages. In addition to the fact that NANOG and GATA6 are factors that are involved in early embryonic development, we believe that the administration of extrapituitary gonadotropins and antioxidants contributed to the increase in gene expression.

PROTECTIVE EFFECTS OF GRAPE SEED EXTRACT (VITIS VINIFERA) AGAINST CISPLATIN-INDUCED LIVER DAMAGE IN RABBITS. (HISTOLOGICAL AND HISTOPATHOLOGICAL STUDY)

Cisplatin is a chemotherapeutic drug used in the treatment of various cancer types. It can be considered a double-edged sword. It is a potent anticancer agent at the same time has toxic effect on various tissues as it causes hepatotoxicity. It was determined to cause liver toxicity and to weaken the antioxidant defense systems in liver. A decrease in antioxidant enzymes resulted from cisplatin induced tissue toxicity. Moreover, the development of therapies to prevent the appearance of cisplatin- induced tissue toxicities has focused on administration of antioxidants along with cisplatin treatment. The grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Therefore, the aim of present study was designed to investigate the protective effects of grape seed extract on the liver damage in cisplatin treated rabbits. Twenty seven healthy rabbits of local mixed breed were selected, divided into three equal groups, the first group (CON group) served as control and received a single intraperitoneal injection of normal saline solution once per week for 6 weeks; the second group (CIS group) were treated with therapeutic dose of cisplatin intraperitoneally once per week for six weeks; the third group (CIS+GSE group) served as protective group and was concomitantly treated with grape seeds extract by oral gavages and cisplatin injection intraperitoneally once per week for six successive weeks. Administration of grape seeds extract by oral gavages starting from the first day of the experiment for 6 consecutive days before and 6 consecutive days after the cisplatin injection and continued daily for 6 weeks. The histopathological findings present in current study showed that cisplatin toxicity produced significant structural changes in the liver of CIS group, cisplatin treated group, in the form of prominent disorganized architecture and loss of liver lobulation, distortion of the arrangement of parenchyma of the liver, loss of radial arrangement of sinusoids from the central vein of the liver, Dilatation and congestion of central veins, sinusoids and portal traids, degenerative changes in hepatocytes and pyknotic nuclei indicating necrosis. Marked vacuolar degeneration mainly hydropic ballooning degeneration and hyper activation of Kupffer cells and inflammatory cellular infiltrations were also observed. This finding reflected the cytotoxic effects of cisplatin in hepatic tissue. While, in the sections from the liver of animals received therapeutic dose of cisplatin and treated by grape seed extract, group (CIS+GSE) clearly showed that there was a significant alleviated hepatotoxicity, since histopathological changes were markedly less pronounced compared to animals treated with cisplatin alone. Therefore, and based on our findings, the grape seed extract contributes significantly to the improvement of histological alterations in rabbit liver caused by cisplatin.

Targeted Therapy of Acute Liver Injury via Cryptotanshinone-Loaded Biomimetic Nanoparticles Derived from Mesenchymal Stromal Cells Driven by Homing.

Acute liver injury (ALI) has the potential to compromise hepatic function rapidly, with severe cases posing a considerable threat to human health and wellbeing. Conventional treatments, such as the oral administration of antioxidants, can inadvertently lead to liver toxicity and other unwanted side effects. Mesenchymal stromal cells (MSCs) can target therapeutic agents directly to inflammatory sites owing to their homing effect, and they offer a promising avenue for the treatment of ALI. However, the efficacy and feasibility of these live cell products are hampered by challenges associated with delivery pathways and safety concerns. Therefore, in this work, MSC membranes were ingeniously harnessed as protective shells to encapsulate synthesized PLGA nanoparticle cores (PLGA/MSCs). This strategic approach enabled nanoparticles to simulate endogenous substances and yielded a core-shell nano-biomimetic structure. The biomimetic nanocarrier remarkably maintained the homing ability of MSCs to inflammatory sites. In this study, cryptotanshinone (CPT)-loaded PLGA/MSCs (CPT@PLGA/MSC) were prepared. These nanoparticles can be effectively internalized by LO2 cells. They reduced cellular oxidative stress and elevated inflammatory levels. In vivo results suggested that, after intravenous administration, CPT@PLGA/MSCs significantly reduced uptake by the reticuloendothelial system and immune recognition compared to PLGA nanoparticles without MSC membrane coatings, subsequently resulting in their targeted and enhanced accumulation in the liver. The effectiveness of CPT@PLGA/MSCs in alleviating carbon tetrachloride-induced oxidative stress and inflammation in a mouse model was unequivocally demonstrated through comprehensive histological examination and liver function tests. This study introduces a pioneering strategy with substantial potential for ALI treatment.