Histopathological Damage Research Articles

Evaluation of pathways involved in the protective effect of trans sodium crocetinate against contrast-induced nephropathy in rats.

Contrast-induced nephropathy (CIN) is the most important side effect following contrast media application. The purpose of this study was to investigate the nephroprotective effects of trans sodium crocetinate (TSC) against sodium amidotrizoate/meglumine amidotrizoate (SAMA).Wistar rats were classified into eight groups (n = 6, male, 220-250g) including (1) sham, injection of solvents (intraperitoneally; i.p.), (2) premedication-control, N(ω)-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, i.p.) + indomethacin (IND, 10mg/kg, i.p.), (3) model (L-NAME + IND + SAMA (12.5ml/kg, i.p.)), (4-6) TSC 10, 20, and 40mg/kg/day, 7 days, i.p., and L-NAME + IND + SAMA, (7) N-acetylcysteine (NAC, 125mg/kg/day, 7 days, i.p.) and L-NAME + IND + SAMA, (8) TSC alone (40mg/kg/day, 7 days, i.p.). Rats were injected with L-NAME, IND, and SAMA 40h after water deprivation.SAMA caused the enhancement of histopathological damage in kidney tissue, biochemical factors (serum blood urea nitrogen and creatinine), and oxidative stress. Moreover, SAMA increased inflammation (TNF-α), apoptosis proteins(Caspase 3-cleaved and Bax/Bcl-2 ratio), and autophagy markers (Beclin-1 and LC3 II/I ratio). TSC declined biochemical factors and oxidative stress. Also, TSC 40mg/kg decreased histopathological damage, inflammation, apoptosis, and autophagy markers.This study demonstrated that TSC has nephroprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic properties, as well as regulating autophagy.

Epimedium polysaccharides ameliorate ulcerative colitis by inhibiting oxidative stress and regulating autophagy.

Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved. The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression. In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.

Ameliorative Potential of Sudachitin Against Paraquat Induced Renal Toxicity in Rats Via Regulating Nrf2/Keap1 Pathway: An Inflammatory, Apoptotic and Histopathological Assessment

AbstractParaquat (PQ) is a noxious herbicide which is well known for its adverse effects on vital organs including kidneys. Sudachitin (SCN) is a plant derived flavone that is obtained from Citrus sudachi and demonstrates a range of pharmacological potentials. This investigation was executed to assess the protective effects of SCN to counteract PQ instigated renal damage in albino rats (Rattus norvegicus). Twenty‐four rats were apportioned in 4 different groups i. e., control group, PQ (5 mg/kg) intoxicated group, PQ (5 mg/kg)+SCN (20 mg/kg) cotreated group and SCN (20 mg/kg) only administrated group. Our findings revealed that exposure to PQ reduced the expressions of Nrf2 (nuclear factor erythroid 2–related factor 2) and its cytoprotective genes while escalating the expression of keap1. Furthermore, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), heme‐oxygenase‐1 (HO‐1) and glutathione (GSH) contents while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Moreover, PQ exposure significantly increased the levels of neutrophil gelatinous‐associated lipocalin (NGAL), urea, kidney injury molecule‐1(KIM‐1) as well as creatine while reducing creatine clearance. Additionally, PQ upregulated the levels of inflammatory markers including interleukin‐6 (IL‐6), tumor necrosis‐ α (TNF‐ α), nuclear factor‐ κB (NF‐κB), interleukin 1beta (IL‐1β), and cyclo‐oxygenase‐2 (COX‐2). Moreover, PQ administration upregulated the expression of Bax (Bcl‐2–associated X protein) and (cysteine–aspartic acid protease) Caspase‐3 while downregulating the expressions of (B‐cell lymphoma 2 protein) Bcl‐2. Besides, PQ exposure prompted various histopathological damages in renal tissues. Nonetheless, SCN substantially restored aforementioned alterations in the renal tissues owing to its anti‐oxidative, anti‐inflammatory and anti‐apoptotic potential.

Dabigatran attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and the NF-kB/IL-1β/MCP-1 and TLR4/NLRP3 signaling pathways.

This study examines Dabigatran's (Dab) capacity to mitigate methotrexate (MTX)-induced coagulation disorders and endothelial dysfunction, while exploring its effects on oxidative stress and inflammatory pathways (NF-kB/IL-1β/MCP-1, TLR4/NLRP3) in reducing hepatotoxicity. Rats were assigned to four groups: a control group receiving saline intraperitoneally (i.p.); an MTX group with a single MTX dose (20 mg/kg, i.p.) to induce hepatotoxicity; and two pretreatment groups receiving Dab orally at 15 mg/kg and 25 mg/kg for seven days before and 4 days after MTX administration. MTX-treated rats showed significant increases in liver enzymes (ALT, AST, ALP) and reductions in antioxidant enzymes (SOD, GSH), along with elevated coagulation parameters (tissue factor (TF), thrombin, fibrin, plasminogen activator inhibitor-1 (PAI-1)), leading to coagulation disorders. Endothelial dysfunction was evident with reduced eNOS expression, while inflammation increased through elevated iNOS, ICAM-1, and pro-inflammatory cytokines (MPO, NF-kB, TNF-α, IL-1β, MCP-1), alongside activation of the TLR4/NLRP3 inflammasome pathway and decreased IL-10 (p < 0.05). Immunohistochemistry revealed increased cytochrome c and caspase-3 expression, with histopathological damage. Dabigatran mitigated these effects, downregulating liver enzymes, modulating coagulation factors, restoring eNOS levels, and reducing histopathological and inflammatory markers. Dabigatran demonstrates significant therapeutic potential in alleviating methotrexate-induced hepatotoxicity through its antioxidant, anti-inflammatory, anticoagulant, and anti-apoptotic effects. Its regulation of coagulation parameters and endothelial function suggests a protective role against tissue damage, warranting further investigation.

Chlorogenic Acid Alleviates Inflammation and Fibrosis in a Murine Model of Bleomycin-Induced Systemic Sclerosis: A Histological Analysis

Background/Objectives: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by cutaneous and visceral fibrosis, vascular alterations, and a persistent inflammatory response. Despite advances in understanding the pathogenic mechanisms underlying SSc, current therapeutic options remain limited. Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and has shown antioxidant, anti-inflammatory, and antifibrotic properties. However, its therapeutic potential in SSc has not been investigated yet. Methods: A model of SSc was established by administering bleomycin (BLM) at 100 U/kg to CD1 mice via an osmotic minipump. After fourteen days of BLM administration, CGA (60 mg/kg) was intragastric administered on consecutive days until day 20. On day 21, all mice were sacrificed. The effect of CGA was histologically evaluated by hematoxylin and eosin and Masson’s trichrome staining. Results: CGA treatment significantly attenuated dermal fibrosis in the BLM-induced mice model of SSc by reducing histopathological damage, including increased dermal thickness, inflammation, collagen deposition, and SSc-associated pulmonary fibrosis. Conclusions: The evidence shows that CGA attenuates BLM-induced SSc in a mice model and strongly suggests that CGA may be a promising compound for the treatment of SSc.

Pulmonary Flora-Derived Lipopolysaccharide Mediates Lung-Brain Axis through Activating Microglia Involved in Polystyrene Microplastic-Induced Cognitive Dysfunction.

Microplastics (MPs) have been detected in the atmospheric and the human respiratory system, indicating that the respiratory tract is a significant exposure route for MPs. However, the effect of inhaled MPs on cognitive function has not been adequately studied. Here, a C57BL/6 J mouse model of inhalation exposure to polystyrene MPs (PS-MPs, 5 µm, 60 d) is established by intratracheal instillation. Interestingly, in vivo fluorescence imaging and transmission electron microscopy reveal that PS-MPs do not accumulate in the brain. However, behavioral experiments shows that cognitive function of mice is impaired, accompanied by histopathological damage of lung and brain tissue. Transcriptomic studies in hippocampal and lung tissue have demonstrated key neuroplasticity factors as well as cognitive deficits linked to lung injury, respectively. Mechanistically, the lung-brain axis plays a central role in PS-MPs-induced neurological damage, as demonstrated by pulmonary flora transplantation, lipopolysaccharide (LPS) intervention, and cell co-culture experiments. Together, inhalation of PS-MPs reduces cognitive function by altering the composition of pulmonary flora to produce more LPS and promoting M1 polarization of microglia, which provides new insights into the mechanism of nerve damage caused by inhaled MPs and also sheds new light on the prevention of neurotoxicity of environmental pollutants.

Cichlidogyrosis in tropical aquaculture: pathological effects and infection dynamics in Nile tilapia Oreochromis niloticus, a case study in Campeche, Mexico

ABSTRACT Cichlidogyrus spp. are dactylogyridean ectoparasites of wild cichlids and cultured Nile tilapia that occur in several regions worldwide. They can be abundant in intensive Nile tilapia culture and cause mild to severe gill pathogenic effects that frequently are overlooked. From January to June 2018, a follow-up study was conducted on an intensive farm where 360 Nile tilapia were sampled and analyzed throughout a six-month culture cycle. During the survey, a population of monogeneans was observed to increase steadily over the course of the production cycle. To corroborate the status of these parasites, 13 additional farms were visited from January to April 2020, where a total of 130 Nile tilapia were examined. This secondary sampling aimed to identify and corroborate the dominant monogenean species and the infection dynamics, including the associated histopathological damages. Nine species of the genus Cichlidogyrus (Cichlidogyrus sp. C. bifurcatus, C. dossoui, C. halli, C. haplochromii, C. longicornis, C. sclerosus, C. thurstonae and C. tilapiae) were recovered from the gills and identified. Overall, Cichlidogyrus sclerosus was the most prevalent and abundant parasite. Also, significant differences were found in the monthly prevalence and intensity of C. sclerosus, especially in the fourth month of culture when the population peaked (Chi-square, p < .001; p < .001, respectively). Correlations were observed between temperature, nitrite, and C. sclerosus intensity. Four left gill arches of 130 Nile tilapia collected in the farms were removed and fixed at 10% formalin for histopathological examination. Histological alterations in gills tissues were graded by severity scores. Gills, at the site of monogenean attachments, showed mucus secretion, hyperplasia, hypertrophy, and lamellar fusion involving mucous cells, depending on the intensity of the damage.

Effect of Rhei Radix Et Rhizome on treatment of polycystic ovary syndrome by regulating PI3K/AKT pathway and targeting EGFR/ALB in rats

Ethnopharmacological relevanceAbnormal endocrine metabolism caused by polycystic ovary syndrome (PCOS) poses a serious risk to reproductive health in females. According to Traditional Chinese Medicine (TCM) theories, the leading causes of PCOS include turbid phlegm, blood stasis and stagnation of liver Qi. Rhei Radix Et Rhizome is widely used in TCM to attack stagnation, clear damp heat, relieve fire. Rhei Radix Et Rhizome is an important part of the TCM formulas for the treatment of PCOS, which has a long history of medicinal use. However, the specific effect and mechanisms of Rhei Radix Et Rhizome on PCOS have yet to be elucidated. Aim of the studyThe object of this study aimed to investigate the effect and its pharmacological mechanism of Rhei Radix Et Rhizome on the treatment of polycystic ovary syndrome. MethodsPCOS was induced in female Sprague Dawley (SD) rats by administering letrozole (1 mg/kg, per orally, p.o.) for 21 days, then treated with Rhei Radix Et Rhizome at doses of 0.6g/kg or 1.2g/kg. Rats weight, blood glucose and estrus period are measured, and serum hormone include free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and ovarian lesions were observed to determine the effects of Rhei Radix Et Rhizome. Network pharmacology and molecular docking predicted the targets of Rhei Radix Et Rhizome on PCOS. Epidermal growth factor receptor (EGFR), albumin (ALB), PI3K and P-AKT/AKT protein expression levels in ovarian tissues were assessed by Western blot. ResultsRhei Radix Et Rhizome reduce abnormal weight and fasting blood glucose induced by letrozole (n=5, p < 0.01), and improve the disturbed estrus cycle, reduce T, LH levels and LH/FSH ratio of PCOS rats (n=4, p < 0.01). In addition, it alleviates the polycystic changes of ovaries in PCOS rats and reduces ovarian histopathological damage (n=4, p < 0.01). Additionally, the core active components of Rhei Radix Et Rhizome for PCOS include Sennoside D_qt, Procyanidin B-5,3'-O-gallate, and Mutatochrome, which strongly bind to core therapeutic targets ALB and EGFR. Furthermore, the treatment reduces the increase of EGFR and ALB induced by letrozole (n=4, p < 0.01). KEGG pathway enrichment analysis highlights endocrine resistance and prolactin signaling pathway, in both of which the PI3K/AKT pathway plays a crucial role. Our results show Rhei Radix Et Rhizome rescue the abnormal expression of PI3K/AKT pathway in PCOS rats (n=4, p < 0.01). However, no significant dose-dependent relationship was observed in the tested dose range for the above experiments. ConclusionThese findings suggest that Rhei Radix Et Rhizome can regulate the PI3K/AKT pathway and target EGFR and ALB to treat polycystic ovary syndrome in rats. This study provides a scientific basis for the use of Rhei Radix Et Rhizome in the treatment of PCOS and highlights its potential mechanism through modulation of the PI3K/AKT pathway.

Sevoflurane Affects Myocardial Autophagy Levels After Myocardial Ischemia Reperfusion Injury via the microRNA-542-3p/ADAM9 Axis.

This research focused on investigating the effects of sevoflurane (Sev) on myocardial autophagy levels after myocardial ischemia reperfusion (I/R) injury via the microRNA-542-3p (miR-542-3p)/ADAM9 axis. Mice underwent 30min occlusion of the left anterior descending coronary (LAD) followed by 2h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by echocardiography. Cardiac markers and oxidative stress factors were evaluated by ELISA. Autophagy-associated factors were detected by western blot. Relationship between miR-542-3p and ADAM9 was tested by dual-luciferase reporter gene assay, RT-qPCR, and western blot. Sev treatment ameliorated cardiac dysfunction, myocardial oxidative stress, and histopathological damages, decreased myocardial infarction size and myocardial apoptotic cells after myocardial I/R injury. Sev treatment elevated miR-542-3p expression and decreased ADAM9 expression in myocardial tissues after myocardial I/R injury. miR-542-3p overexpression could enhance the ameliorative effects of Sev on myocardial injury and myocardial autophagy in I/R mice. miR-542-3p targeted and negatively regulated ADAM9 expression. ADAM9 overexpression reversed the ameliorative effects of miR-542-3p up-regulation on myocardial injury and myocardial autophagy in Sev-treated I/R mice. Sev treatment could ameliorate myocardial injury and myocardial autophagy in I/R mice, mediated by mechanisms that include miR-542-3p up-regulation and ADAM9 down-regulation.

Temperature alters antioxidant status and induces cell damage in the Amazonian fish tambaqui

Since Amazonian fish live close to their maximum thermal limits, this makes them vulnerable to the effects of global warming. The aim of this study was to evaluate the oxidative stress and antioxidant enzymatic and biochemical responses of the plasma, liver and muscle of tambaqui (Colossoma macropomum) exposed to a rising gradient of water temperature. One hundred and twenty (N=120) juvenile tambaqui were exposed to four temperature levels, these being: the environmental temperature of the season (Tenv – 25.7-30 ºC), 31 ºC, 34 ºC and 37 ºC, following a completely randomized design with three replicates for a period of 60 days. Liver and muscle samples were used to determine the levels of the enzymes superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and lipid peroxidation (LPO). Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. A histopathological damage assessment (HAI) was performed using liver samples and the results showed an increase in lipid peroxidation in the muscle and liver of animals kept at 37 ºC in relation to other temperatures. Enzyme responses were tissue-specific in the liver and muscle. In the liver, the reduction of CAT, SOD and GPx levels of the animals was observed at 37 ºC compared to those maintained at Tenv and SOD and GPx in relation to animals maintained at 31 and 34 ºC. The GPx enzyme showed higher activity at 34 and 37 ºC compared to the other evaluated temperatures. At 37 ºC, plasma levels of ALT and AST were higher than the other temperatures evaluated, as well as an increase in histopathological damage. In this way, in a scenario of warming of the waters of the Amazon or even of the systems used for rearing of the species, the tambaqui will be able to cope with temperatures of up to 34 ºC, without affecting its antioxidant capacity. However, at 37 ºC, oxidative stress levels and increased liver damage suggest a reduction in antioxidant capacity due to tissue impairment of the organ and general loss of animal performance as it approaches the upper thermal limit of the species.

Effects of sitagliptin and L-theanine combination therapy on testicular tissue in rats with experimental diabetes

This study examines the impact of the combination of sitagliptin and L-theanine on the testis tissue of rats with experimental diabetes. Diabetes mellitus, a chronic metabolic illness, significantly reduces quality of life and can cause male infertility by decreasing sperm count, motility, and testosterone levels. Rats were allocated to five separate groups: control, diabetes, L-theanine, sitagliptin, and combination therapy. The measurements encompassed blood glucose levels, body weight, serum insulin levels, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The histological examination of testicular tissue was conducted using H&E, PASH, caspase-12, and PCNA staining techniques, in addition to a TUNEL assay to detect apoptosis. Levels of oxidative stress indicators, including glutathione peroxidase (GPX), malondialdehyde (MDA), and catalase, were also evaluated. The results showed that the group of individuals with diabetes had significantly higher levels of blood glucose, apoptotic indices, GPX, catalase, and MDA levels and activities in comparison with the control group. Although both the L-theanine and sitagliptin groups exhibited some improvement, the combination therapy demonstrated the most significant decrease in histopathological damage and apoptotic markers. These results indicate that the combination of sitagliptin and L-theanine may significantly decrease testicular damage caused by diabetes, making it a promising therapeutic strategy.

Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model.

In this study, we aimed to explore the role of Tarm1 in juvenile mice with dextran sulfate sodium (DSS)-induced colitis and elucidate the mechanisms that affect intestinal barrier function. A DSS-induced pediatric inflammatory bowel disease mouse model was established using 4-week-old juvenile mice. Disease activity index and histopathological damage scores were determined using hematoxylin and eosin (H&E) staining. Tarm1, F4/80, CD68, and CD86 levels were detected using qPCR, western blotting, and immunofluorescence. Trans epithelial electric resistance (TEER) was detected using the transwell assay. Results revealed that juvenile colitis mice fed 4% DSS drinking water had increased Tarm1 expression in the colon tissue, increased macrophage M1 polarization, higher expression of pro-inflammatory cytokines, and an impaired intestinal mucosal barrier, compared with the control group. Tarm1-knockdown RAW264.7 cells inhibited lipopolysaccharide (LPS)-induced M1 polarization and attenuated barrier damage in co-cultured intestinal epithelial cells. Tarm1 expression was increased in colonic tissues of juvenile mice with colitis, and LPS-induced M1 polarization and intestinal barrier damage were attenuated in Tarm1-knockdown RAW264.7 cells. This suggests that attenuation of Tarm1 expression is a potential target for pediatric inflammatory bowel disease therapy.

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.

Olive Oil's protective potential against cyclophosphamide-induced nephrotoxicity in Swiss albino rats

Background: Cyclophosphamide is a widely used chemotherapy drug, known for its cytotoxic and mutagenic effects on mammalian tissues and cells. Olive oil, rich in antioxidants, has potential protective effects against drug-induced organ damage. This study investigates the protective role of olive oil against cyclophosphamide-induced toxicity in mice. Objective: To evaluate the protective effects of olive oil against cyclophosphamide-induced kidney toxicity in rats. Material and Method: Male albino mice (n=9) were divided into three groups: Control, Cyclophosphamide (150 mg/kg), and Cyclophosphamide (150 mg/kg) + Olive Oil (200 mg/kg). After one week of treatment, kidney tissues were collected and stained with hematoxylin and Eosin for histopathological analysis. Results: The administration of olive oil led to a significant decrease in cellular damage of the kidney tissue. In this study the histopathological examination revealed marked improvement in kidney tissue architecture, with reduced cellular damage, inflammation, and fibrosis compared to the group treated with cyclophosphamide alone. These findings suggest that olive oil has a protective effect against cyclophosphamide-induced hepatic and renal toxicity in mice. Conclusion: Cyclophosphamide caused significant histopathological damage to kidney tissues in mice. Co-administration of olive oil mitigated these adverse effects, likely due to its antioxidant properties. This suggests that olive oil may serve as a protective adjunct in cyclophosphamide chemotherapy.

Apple Polyphenol Extracts Attenuated Depressive-Like Behaviors of High-Sucrose Diet Feeding Mice by Farnesoid X Receptor-Mediated Modulation of Bile Acid Circulation within the Liver-Gut-Brain Axis.

Although the association between high-sugar diets and depression has been verified, few studies have explored the antidepressant mechanisms of apple polyphenol extracts (APE). Therefore, fifty-four C57BL/6 male mice aged 5 weeks were randomly assigned into five groups: the control group with the standard diet (CON), the constant high-sucrose diet group (HSD), the "2 + 5" alternate diet group (A-HSD), and the 500 mg/(kg·bw) APE treatment for the HSD group (APE) and the A-HSD group (A-APE), respectively. The data of hypothalamic-pituitary-adrenal (HPA) axis function and behavioral experiments confirmed the success in the establishment of depression-like mouse models in both HSD and A-HSD groups, which were significantly alleviated after APE treatment. Meanwhile, APE reduced serum levels of corticosterone and adrenocorticotrophic hormone, alleviated histopathological damage of the liver, colon, and brain, respectively, elevated the protein expressions of Occludin, ZO-1, and MUC-2, and decreased Firmicutes/Bacteroidota ratio and Dubosiella abundance with the increased microbiota of Tannerellaceae_unclassified, Muribaculum, and Lachnospiraceae_unclassified. Moreover, APE treatment reduced Farnesoid X receptor (FXR) protein levels along with the increased expressions of CYP7A1 and TGR5, lowered the contents of serum and fecal total bile acids, and modulated fecal BA compositions, particularly glycocholic acid (GCA) and isolithocholic acid (ILCA). Thus, both the constant and alternate high-sucrose diets successfully induced depression-like behaviors in mice, and APE might be a potential nutraceutical to attenuate high-sucrose diet-induced depression by regulating BAs circulation within the liver-gut-brain axis mediated by FXR.

Effect of castor oil on esophageal stricture in rats and expression of ST-2, neopterin proteins in corrosive burn model

Corrosive esophageal burn (CEB) is a disease with high mortality and morbidity rates. The aim of this study was to determine the efficacy of castor oil, in preventing stricture development at the experimental CEB model. In addition to studying standard histopathological damage data, neopterin, IL-33, and ST-2 proteins were also studied for the first time. Fifty Wistar-Albino rats were divided into randomized 5 groups. [Sham group (G1) (n:10), Control group (G2) (n:10), Early Stage Topical Application group (G3)(n:10), Late Stage Topical Application group (G4) (n:10), Oral Application group (G5) (n:10)]. Weight measurement, esophageal length, histopathological damage score (HDS) and total stenosis score (TSS), tissue caspase-3 and VEGF staining, tissue hydroxyproline (HYP), blood TNF-alpha, IL-6, IL-33, Neopterin, and ST-2 levels were measured. In the castor oil application groups, weight gain was observed, the acute phase reaction decreased, submucosal/tunica muscularis fibrosis (TMF) and muscularis mucosal damage (MMD) were reduced, and TSS and HDS decreased. While no significant difference was detected in the ST-2 protein, which was used for the first time in this study model, a significant increase in neopterin protein was observed in the application groups. Results indicate the nutritional contribution of castor oil, as well as its tissue healing and esophageal stricture-preventing efficacy at histopathological and immune-histochemical levels.

Evaluation of protective potency of coconut oil-based probiotic against antibiotic-induced compromised gastrointestinal attributes and associated complications in Swiss albino mice

Background: Antibiotic-induced gastrointestinal toxicity is a major concern globally. The gut-organ axis has been explicitly studied, and hence, any damage to the gut ecosystem directly or indirectly manifests into compromised multi-organ functions. Therefore, the present study was designed to explore the protective potency of coconut oil-probiotic (C-PRO) against antibiotic-induced compromised gastrointestinal attributes and associated complications. Methods: Animals were divided into 5 groups (n=6). Normal saline was given to the control group; the antibiotic cocktail was given to the antibiotic group. In the treatment group, low and high doses of C-PRO were given post-antibiotic treatment. In the per se group, only a high dose of C-PRO was given. After 28 days, animals were studied for neurobehavioral parameters and scarified. Blood and organs were collected and stored for histopathological, immune histochemical, and biochemical analysis. Results: Antibiotic treatment reduced body weight, increased oxidative stress, and caused histopathological damage to the stomach, duodenum, colon, brain, heart, liver, lungs, kidney, spleen, and testis. It also altered biochemical parameters such as lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), albumin, creatinine, urea, uric acid, and blood urea nitrogen (BUN). Additionally, Antibiotic exposure in mice exhibited depressive-like behaviour and declined cognitive function. The treatment with a low dose of C-PROs showed negligible protective effect, whereas a high dose of C-PRO effectively reversed the structural, biochemical, and neurobehavioral attributes toward normal. Conclusions: We conclude that the synergistic effect of coconut oil and probiotics, which have potent antioxidant and anti-inflammatory effects, might be responsible for multidimensional protective effects against compromised gastrointestinal attributes and associated complications.

Isoliquiritigenin alleviates cerebral ischemia-reperfusion injury by reducing oxidative stress and ameliorating mitochondrial dysfunction via activating the Nrf2 pathway

Cerebral ischemia-reperfusion injury (CIRI) refers to a secondary brain injury that occurs when blood supply is restored to ischemic brain tissue and is one of the leading causes of adult disability and mortality. Multiple pathological mechanisms are involved in the progression of CIRI, including neuronal oxidative stress and mitochondrial dysfunction. Isoliquiritigenin (ISL) has been preliminarily reported to have potential neuroprotective effects on rats subjected to cerebral ischemic insult. However, the protective mechanisms of ISL have not been elucidated. This study aims to further investigate the effects of ISL-mediated neuroprotection and elucidate the underlying molecular mechanism. The findings indicate that ISL treatment significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral infarction, neurological deficits, histopathological damage, and neuronal apoptosis in mice. In vitro, ISL effectively mitigated the reduction of cell viability, Na+-K+-ATPase, and MnSOD activities, as well as the degree of DNA damage induced by oxygen-glucose deprivation (OGD) injury in PC12 cells. Mechanistic studies revealed that administration of ISL evidently improved redox homeostasis and restored mitochondrial function via inhibiting oxidative stress injury and ameliorating mitochondrial biogenesis, mitochondrial fusion-fission balance, and mitophagy. Moreover, ISL facilitated the dissociation of Keap1/Nrf2, enhanced the nuclear transfer of Nrf2, and promoted the binding activity of Nrf2 with ARE. Finally, ISL obviously inhibited neuronal apoptosis by activating the Nrf2 pathway and ameliorating mitochondrial dysfunction in mice. Nevertheless, Nrf2 inhibitor brusatol reversed the mitochondrial protective properties and anti-apoptotic effects of ISL both in vivo and in vitro. Overall, our findings revealed that ISL exhibited a profound neuroprotective effect on mice following CIRI insult by reducing oxidative stress and ameliorating mitochondrial dysfunction, which was closely related to the activation of the Nrf2 pathway.

Examining the Cardioprotective Effects of Aerobic Exercise Combined with Crocin or Berberine on Methamphetamine-Induced Heart Damage in Female Rats

Background: While the harmful effects of methamphetamine abuse on the heart are well-known, the solutions to deal with these damages are not well-known. Objectives: This study aimed to investigate whether aerobic exercise combined with supplements such as Crocin and Berberine can potentially protect against methamphetamine-induced changes in the heart tissue of female rats. Methods: Forty-two female rats were randomly assigned into seven groups (n = 6). The groups included healthy control, methamphetamine, methamphetamine + exercise, methamphetamine + Crocin, methamphetamine + Berberine, methamphetamine + exercise + Crocin, and methamphetamine + exercise + Berberine group. Methamphetamine (10 mg/kg) was injected intraperitoneally over five days. The animals were administered Crocin via intraperitoneal injection at 40 mg/kg during a four-week withdrawal period. At the same time, Berberine was dissolved in drinking water at 100 mg/kg concentration. The aerobic training consisted of running at 25 m/min for 30 minutes. A light microscope was used to observe the structural changes. Data analysis was performed using non-parametric Kruskal-Wallis and Mann-Whitney U tests by SPSS 26, with a significance level of 5%. Results: The results of the study indicate that methamphetamine use causes hyperemia, inflammation, and histopathological damage in the heart cells and tissue (P = 0.001). The combination of exercise with Crocin significantly eliminated methamphetamine-induced heart tissue damage (P = 0.001) and improved cardio-respiratory endurance compared to control (P = 0.004) and methamphetamine (P = 0.01) groups. The combination of aerobic exercise with Berberine removed methamphetamine-induced heart cell damage (P = 0.001), and improved cardio-respiratory endurance compared to control (P = 0.024) and methamphetamine (P = 0.05) groups. In addition, all intervention groups showed a significant reduction in hyperemia and inflammation compared to the methamphetamine group (P = 0.001). Conclusions: A combination of exercise with either Crocin or Berberine supplements demonstrated potential benefits in mitigating some of the harmful structural effects of methamphetamine and improving cardio-respiratory endurance.

Recombinant avian-derived antiviral proteins cIFITM1, cIFITM3, and cViperin as effective adjuvants in inactivated H9N2 subtype avian influenza vaccines

Vaccine adjuvants, serving as non-specific immune enhancers, play a pivotal role in the immunoprevention and control of animal diseases. This study utilized prokaryotic expression systems to express and purify chicken-derived cIFITM1, cIFITM3, and cViperin, which were then formulated as adjuvants with H9N2 avian influenza virus antigens to create inactivated vaccines. These vaccines were administered to SPF chickens to investigate their immunopotentiating functions. Additionally, the proteins were assessed for their ability to act as standalone immune enhancers. The results demonstrated that cIFITM1, cIFITM3, and cViperin significantly elevated serum hemagglutination inhibition (HI) antibody titers. Notably, when used individually, these proteins markedly enhanced the antiviral capabilities of challenged chickens, leading to alleviated clinical symptoms, reduced tracheal virus replication, diminished virus shedding, and lessened histopathological damage, with cIFITM1 exhibiting the most pronounced effect. Furthermore, the protective efficacy of two H9N2 recombinant virus inactivated vaccines supplemented with cIFITM1 adjuvant was validated, achieving a 100 % vaccine protection efficiency. In conclusion, cIFITM1, cIFITM3, and cViperin as adjuvants for influenza vaccines effectively inhibit virus replication and shedding, highlighting their significant potential in influenza prevention and control.