Histopathological Damage Scores Research Articles

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.

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.

Investigating the Hepatic Response to Orlistat and White Tea in Rats on a High-Fat Diet.

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects.

Evaluation of Endoplasmic Reticulum Stress in an Experimental Intestinal Ischemia-Reperfusion Model in Rats: The Role of Ozone Therapy and Trimetazidine.

The objective of the study was to assess the impact of ozone (O3) and trimetazidine on the intestines following ischemia-reperfusion (I/R) injury through the investigation of endoplasmic reticulum stress. Forty Sprague Dawley rats were separated into five groups. The groups were named as follows: control, O3, I/R, I/R + trimetazidine (TMZ), and I/R + O3. The control group had laparotomy and exploration of the superior mesenteric artery (SMA) only. Furthermore, alongside laparotomy and SMA exploration, an intraperitoneal (i.p.) administration of a 0.7 mg/kg ozone-oxygen (O3-O2) combination was given to the O3 group. In the experimental groups, the SMA was blocked with the silk suture ligation technique for a duration of 1 h and then restored to normal blood flow for another hour. In the I/R + O3 group, ozone was delivered i.p. at a dosage of 0.7 mg/kg, 30 min after ischemia. In the I/R + TMZ group, a dose of 20 mg/kg/day of trimetazidine was administered orally via gavage for a duration of 7 days, beginning 1 week prior to the induction of ischemia. Intestinal tissues were taken to assess indicators of intestinal mucosal injury and oxidative stress. The level of the lipid peroxidation marker malondialdehyde (MDA) was significantly reduced in the experimental groups as compared to the I/R group (p < 0.05). The experimental groups had considerably greater levels of glutathione (GSH), which reflects antioxidant capacity, compared to the I/R group (p < 0.05). Nevertheless, the concentration of GSH was observed to be increased in the I/R + O3 group in comparison to the I/R + TMZ group (p < 0.05). The histopathological damage score showed a substantial decrease in the experimental groups as compared to the I/R group (p < 0.05). The I/R + O3 group had the lowest injury score. The experimental groups exhibited significantly reduced positivity of the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78 compared to the I/R group (p < 0.05). The findings provide evidence for the potential advantages of utilizing ozone therapy in the treatment of intestinal ischemia-reperfusion injury. Additionally, they propose that ozone should be assessed in more extensive clinical trials in the future as a therapeutic agent that can disrupt endoplasmic reticulum stress.

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury.

Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

Astragalus mongholicus Bunge extract improves ulcerative colitis by promoting PLCB2 to inhibit colonic epithelial cell pyroptosis

Ethnopharmacological relevanceAstragalus mongholicus Bunge (AM) and its active ingredients are mainly used for anti-inflammatory, antiviral, antioxidant, immune regulation, cardiovascular and nervous system protection, anti-cancer, anti-tumor and so on. Aim of the studyTo explore the Astragalus mongholicus Bunge extract pharmacological mechanisms and biology processes which improves ulcerative colitis (UC). Materials and methodsDextran sulfate sodium (DSS)-induced UC models in C57BL/6 mice were established, and the mice were treated with Astragalus mongholicus Bunge extract or salazosulfapyridine (SASP). DSS-induced mice- and human-derived colonic epithelial cell lines were used to reveal the inflammatory environment of UC. After treatment with Astragalus mongholicus Bunge extract, the expression of phospholipase C-β 2 (PLCB2) in the cells was detected by quantitative real-time PCR (qRT-PCR), and cell proliferative activity was detected by cell counting kit 8 (CCK-8) assay. Finally, the levels of pyroptosis-related inflammatory factors in cell culture supernatants was detected by ELISA. ResultsTreatment of UC mice with Astragalus mongholicus Bunge extract do significantly improved DAI scores and histopathological damage scores, and decreased the levels of Eotaxin, GCSF, KC, MCP-1, TNF-α, and IL-6. Besides, Astragalus mongholicus Bunge extract inhibited the expression of nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3), cleaved Caspase-1, and GSDMD-N in the colonic tissues, and reduced the levels of inflammation-related factors IL-1β and IL-18 in serum and tissues. In vitro, Astragalus mongholicus Bunge extract partially reversed the DSS-induced reduction of PLCB2 expression in CP-M030 and NCM460, promoted cell proliferative activity, and reduced the levels of IL-1β and IL-18. ConclusionsIn DDS-induced UC mice, Astragalus mongholicus Bunge extract improves ulcerative colitis by inhibiting colonic epithelial cell pyroptosis through PLCB2 promotion.

Histological and biochemical effects of an ethanolic extract of Myrtus communis leaf on the pancreases of rats fed high fat diets

ABSTRACT We investigated the effects of an ethanolic extract of Myrtus communis subsp. communis (MC) leaves on the pancreases of rats fed with a high fat diet (HFD). Wistar albino rats were fed either with standard lab chow (Control group) or with a 45% fat diet (HFD and HFD+MC groups) for 4 months, with the MC extract (100 mg/kg) being administered by orogastric gavage to rats in the HFD+MC group during the last month. Blood and pancreas samples were collected from all experimental groups at the end of the study. Insulin and leptin levels, and the lipid profile, were analyzed in the blood serum. Pancreatic injury was assessed histologically. Insulin, nuclear factor kappa beta (NF-κB), and alpha-smooth muscle actin (α-SMA) were assessed using immunohistochemistry. Apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunohistochemistry. In addition, oxidant/antioxidant activity was analyzed by biochemical methods. Increased body weight, serum insulin and leptin levels, blood glucose level and pancreatic tissue malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels, myeloperoxidase (MPO) activity and decreased tissue glutathione (GSH) level were observed in the HFD group compared to the Control group, in addition to dyslipidemia. An increased histopathological damage score, pancreatic islet area, insulin, TUNEL, NF-κB and α-SMA immunoreactivity were seen in animals from the HFD group compared to the Control group. However, such pathological changes were reduced in the HFD+MC group. Our data indicate further investigation of MC extract as a therapeutic adjuvant for HFD-induced pancreatic injury, acting via anti-inflammatory and antioxidant mechanisms, is worth carrying out.

Comparison of salpingectomy and tubal detorsion procedures after experimental ischemia-reperfusion injury in a rat fallopian tube model: biochemical and histopathological evaluation

To compare salpingectomy and detorsion procedures and investigate the biochemical and histopathological changes in the fallopian tubes in the experimentally isolated fallopian tube torsion model in rats. Experimental study. Experimental surgery laboratory in a training and research hospital. Twenty-seven Sprague-Dawley rats in the reproductive period. Group 1, control group (n = 6); group 2, bilateral total salpingectomy group after 4 hours of tubal ischemia (n = 7); group 3: 4 hours of bilateral tubal ischemia plus 1 week of reperfusion (n = 7); and group 4, 4-hour period of bilateral tubal ischemia plus 30 days of reperfusion (n = 7). A 22-gauge catheter was administered before and after surgery using methylene blue through the uterine horn of the rat to evaluate tubal patency. Preoperative and postoperative serum antimüllerian hormone (AMH) levels, histopathological examination of the rat tuba uterine and histopathological damage scores, antioxidant compounds (superoxide dismutase [SOD], catalase, and glutathione peroxidase [GSH-Px]), and oxidative stress end product levels (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]). Although a significant difference was observed in the tissue SOD, GSH-Px, MDA, and 8-OHdG values, no significant difference was observed between the groups in serum samples. The tissue SOD and tissue GSH-Px levels in group 2 significantly decreased, and a significant increase was observed in the tissue MDA and 8-OHdG values in group 2. Among the histopathological parameters, epithelial changes, vascular congestion, and the total fallopian tube mean damage score of 4 showed a significant decrease in group 4. When the methylene blue transitions before and after ischemia-reperfusion injury were compared, the values of the methylene blue transition after ischemia-reperfusion injury in groups 2-4 significantly decreased. When the serum AMH levels were analyzed, the postoperative AMH value in group 2 significantly increased. This study reveals that biochemical and histopathological improvement is observed in the fallopian tube tissues gradually when the detorsion procedure is performed for the necrotized tubal tissue instead of salpingectomy. Although there is restoration of epithelial integrity after reperfusion, tubal passage remains absent. This study was approved by the Local Ethics Committee for Animal Experiments of the Health Sciences University, Istanbul Hamidiye Medicine Faculty (approval number 27.05.2022-9269). The study followed the ethics standards recommended by the Declaration of Helsinki.

Investigation of the effects of white tea on liver fibrosis: An experimental animal model.

Liver fibrosis is a common, progressive disease that affects millions of patients worldwide. In this study, it was aimed at investigating the effect of white tea on liver fibrosis in an in-vivo environment by creating an experimental liver fibrosis model on rats. In this study, an experimental liver fibrosis model was created with carbon tetrachloride (CCl4) in Sprague-Dawley rats to investigate the effect of white tea on liver fibrosis. Rats are treated with CCl4 (1 mL/kg) to constitute the liver fibrosis model. White tea was given adlibitum with drinking water. As a result of the study, liver tissue hydroxyproline levels were found to be significantly lower (p = .001) in the white tea group. Histopathologically, it was found that the liver tissue histopathological damage score (LHDS) and fibrosis scoring were significantly lower (p < .001) in the white tea group. However, although it was not statistically significant in the group given white tea, compared with the fibrosis group, it was found that the malondialdehyde (MDA) level in the liver tissues was lower, the glutathione (GSH) level was higher, and the serum alanine aminotransferase (ALT) levels were lower. The study explained the effect of white tea on liver fibrosis and suggested that white tea might be beneficial in reducing the progression of liver fibrosis.

Ameliorating effects of Acacia arabica and Ocimum basilicum on acetic acid-induced ulcerative colitis model through mitigation of inflammation and oxidative stress

IntroductionUlcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum. The disease is characterized by oxidative stress and severe inflammation. Research has shown the anti-oxidative and anti-inflammatory effects induced by consuming the Acacia arabia and Ocimum basilicum. The present study aimed to evaluate the effect of treatment with O. basilicum together with A. arabica on healing, inflammation, and oxidative stress in the course of experimental colitis in rats. MethodsA total number of 50 male rats were selected and randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with a 4 % acetic acid solution. Four days after the colitis induction, the rats were orally treated for the next 4 days with saline or a combination of A. arabica and O. basilicum (1000 mg/kg) or sulfasalazine (100 mg/kg). ResultsAcetic acid-induced colitis increased the colon's macroscopic and histopathological damage scores; increased colon levels of MDA (Malondialdehyde), MPO (Myeloperoxidase), TNF-α (Tissue necrosis factor α), IL6 (Interleukin 6), and IL17 (Interleukin 17); and decreased SOD (Superoxide Dismutase), GPx (Glutathione Peroxidase), and IL10 (Interleukin 10) levels in the treated rats compared with the control group (P < 0.001). Overall, a combination of A. arabica and O. basilicum reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, and MDA, MPO, TNF-α, IL6 (P < 0.001), and IL17 (P < 0.01) levels of the colon. Furthermore, it increased SOD, GPx, and IL10 levels compared to the colitis group (P < 0.01). ConclusionA. arabica and O. basilicum have improving effects on UC by reducing inflammation and oxidative stress.

Therapeutic efficacy of β-sitosterol treatment on Trypanosoma congolense infection, anemia development, and trans-sialidase (TconTS1) gene expression.

African animal trypanosomiasis hinders sustainable livestock productivity in sub-Saharan Africa. About 17 million infected cattle are treated with trypanocides annually but most of the drugs are associated with drawbacks, necessitating the search for a promising chemotherapeutic agent. In this study, the effects of β-sitosterol on Trypanosoma congolense infection were investigated along with its effect on the trans-sialidase gene expressions. Oral treatment with β-sitosterol at 15 and 30 mg/kg body weight (BW) for 14 days significantly (p < 0.05) reduced parasitemia and ameliorated the parasite-induced anemia. Also, the parasite-induced increase in serum urea level and renal histopathological damage scores in addition to renal hypertrophy was significantly (p < 0.05) reverted following treatment with 30 mg/kg BW β-sitosterol. The compound also significantly (p < 0.05) down-regulated the expression of TconTS1 but not TconTS2, TconTS3, and TconTS4. Correlation analysis between free serum sialic acid with the TconTS1 and TconTS2 gene variants revealed negative correlations in the β-sitosterol-treated groups although they were non-significant (p > 0.05) in the group treated with 15 mg/kg BW β-sitosterol. Similarly, a non-significant negative (p > 0.05) correlation between the biomolecule and the TconTS3 and TconTS4 gene variants was observed in the β-sitosterol-treated groups while positive correlations were observed in the infected untreated control group. The observed effect of β-sitosterol on T. congolense infection could make the compound a possible template for the design of novel trypanocides.

Targeting Autophagy, Apoptosis, and SIRT1/Nrf2 Axis with Topiramate Underlies Its Neuroprotective Effect against Cadmium-Evoked Cognitive Deficits in Rats.

Cadmium is an environmental toxicant that instigates cognitive deficits with excessive glutamate excitatory neuroactivity in the brain. Topiramate, a glutamate receptor antagonist, has displayed favorable neuroprotection against epilepsy, cerebral ischemia, and Huntington's disease; however, its effect on cadmium neurotoxicity remains to be investigated. In this study, topiramate was tested for its potential to combat the cognitive deficits induced by cadmium in rats with an emphasis on hippocampal oxidative insult, apoptosis, and autophagy. After topiramate intake (50 mg/kg/day; p.o.) for 8 weeks, behavioral disturbances and molecular changes in the hippocampal area were explored. Herein, Morris water maze, Y-maze, and novel object recognition test revealed that topiramate rescued cadmium-induced memory/learning deficits. Moreover, topiramate significantly lowered hippocampal histopathological damage scores. Mechanistically, topiramate significantly replenished hippocampal GLP-1 and dampened Aβ42 and p-tau neurotoxic cues. Notably, it significantly diminished hippocampal glutamate content and enhanced acetylcholine and GABA neurotransmitters. The behavioral recovery was prompted by hippocampal suppression of the pro-oxidant events with notable activation of SIRT1/Nrf2/HO-1 axis. Moreover, topiramate inactivated GSK-3β and dampened the hippocampal apoptotic changes. In tandem, stimulation of hippocampal pro-autophagy events, including Beclin 1 upregulation, was triggered by topiramate that also activated AMPK/mTOR pathway. Together, the pro-autophagic, antioxidant, and anti-apoptotic features of topiramate contributed to its neuroprotective properties in rats intoxicated with cadmium. Therefore, it may be useful to mitigate cadmium-induced cognitive deficits.

Effects of allium cepa on ovarian torsion-detorsion injury in a rat model.

Ischemia/reperfusion (I/R) damage following detorsion treatment, tissue fibrosis, and adhesions cause secondary tissue damage in the ovaries. Many studies have been evaluated to minimize antioxidant damage in ovarian reserve loss while minimizing I/R damage. However, no study observed long-term effects on the ovarian torsion model in rats. In this study, we evaluated the profibrotic effects of A. cepa on an ovarian torsion model on rats. Group I (n=7) rats were the sham group. Group II (n=7) rats were the torsion group and Group III (n=7) rats were the torsion + A. cepa group. To observe the long-term effects of allium cepa, rats were fed for 21 days. Cellular damage I/R is evaluated by histopathological damage score, and transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) is measured to analyze the profibrotic effect. A. cepa altered cellular damage due to improvement in the histopathological damage score with A. cepa intake. However, the profibrotic mediators TGF-β1 and α-SMA are non- significantly changed by the A. cepa (p=0.477 and p=0.185 respectively). A. cepa is a potent protective on cellular tissue, minimizing I/R damage on ovarian tissue histologically. Our study implies that A. cepa does not affect fibrosis-related mediators in the rat ovary.

Effect of Moringa Leaves Ethanolic Extract (Moringa oleifera, Lam.) on Testicles Histopathological Structure in Metabolic Syndrome Rat Model

&lt;p&gt;&lt;strong&gt;Introduction:&lt;/strong&gt; Metabolic syndrome was a collection of various disorders that can significantly increase the risk of experiencing insulin resistance, atherosclerotic cardiovascular disease, vascular complications, and diabetes mellitus. The detrimental effect of this condition has led to the development of various treatments options, such as Moringa leaves extract (Moringa oleifera), which was suspected to have ameliorative effects. Therefore, this study aimed to determine the effect of Moringa leaves extract on the histopathological appearance of the testes of Wistar rats induced with metabolic syndrome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This was an experimental design study, with a post-test-only control group, involving 30 Wistar rats (Rattus norvegicus). Metabolic syndrome was induced in the samples through the administration of high-fat and fructose feeds along with streptozotocin and nicotinamide. Furthermore, the moringa leaves extract was administered to the treatment groups in different doses of 150, 250, and 350 mg/kg BW. Testicular histopathological damage scores were then assessed on each group. The Kruskal-Wallis test which followed by Mann-Whitney test was used to determine the significant differences between the groups, while the correlation was analyzed using Spearman test.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were significant differences in the histopathological scores between the treatment and control groups. Furthermore, the Wistar rats treated with Moringa extract showed better histopathological scores (2.1±0.64) compared to those without the treatment (2.7±0.54), p&amp;lt;0.05. The results also showed that higher doses of the extract significantly correlated with better outcome in testicular histopathological structure of metabolic syndrome rat model (p=0.000, r=-0.396).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Moringa leaves ethanolic extract treatment improved testicular histopathological appearance in Wistar rats induced with metabolic syndrome.&lt;/p&gt;

Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota

Introduction: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. Methods: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated. Results: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1β and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus. Conclusion: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage.

Methotrexate (MTX) is a cytotoxic immunosuppressant that is widely used in the treatment of tumours, rheumatoid arthritis and psoriasis. This study aims to evaluate the effects of whey proteins on MTX-induced liver and kidney damage by focusing on oxidant–antioxidant systems and eating habits. The study was conducted in four groups of thirty Sprague–Dawley rats (control, control + whey protein concentrate (WPC), MTX, MTX + WPC). A single dose of 20 mg/kg MTX was administered intraperitoneally to the MTX groups. Control and MTX groups were given 2 g/kg WPC by oral gavage every day for 10 d. At the end of day 10, blood samples were drawn and liver and kidney tissues were removed. MTX administration increased the lipid peroxidation level and decreased glutathione level, superoxide dismutase and glutathione-S-transferase activities in the liver and kidney. Administration of WPC significantly reduced the damage caused by MTX in the liver and kidney. While a decrease in serum urea level and an increase in serum creatinine level were detected in the MTX group, WPC administration reversed these results up to control group levels. Administration of WPC to the MTX group significantly reversed the histopathological damage scores of the liver and kidney. WPC administration ameliorated the MTX-induced oxidative damage in the liver and kidney tissues due to its antioxidant properties. Liver and kidney damage can be prevented by using whey proteins as a nutraceutical in MTX therapy. In conclusion, whey proteins demonstrated a protective effect against MTX-induced liver and kidney damage.

The effects of smoking on genotoxic and histopathologic damage in exfoliated oral epithelial cells and the periodontium: A cross-sectional study.

Smoking negatively affects the prognosis of periodontal disease by impairing tissue healing. While micronucleus is the most popular parameter for demonstrating DNA damage, inflammatory cell and vascular densities are the most evaluated parameters for determining histopathologic changes in the periodontium. This study aimed to study the effects of periodontitis and cigarette smoking on genotoxic changes in exfoliated oral epithelial cells and histopathologic changes in periodontal tissue. A cross-sectional study was conducted between November 2018 and July 2019 at a dental university hospital in Turkey, and registered as NCT05484765. Eighty systemically healthy subjects were divided into four groups according to periodontal status and smoking habits: 20 smokers with generalized periodontitis (SGP), 20 nonsmokers with generalized periodontitis (NGP), 20 smokers with healthy periodontium (SHP), and 20 nonsmokers with healthy periodontium (NHP). For each study participant, full-mouth clinical periodontal parameters (CPPs) were measured, smear samples were taken from buccal and gingival mucosa, and periodontal tissue was biopsied from the maxillary molars. Cytogenetic and histopathologic assays (primary and secondary outcomes) were conducted using Feulgen reaction and hematoxylin-eosin staining, respectively. The mean CPPs of healthy periodontium groups were lower than generalized periodontitis groups. No significant differences were found between other groups regarding CPPs. Buccal micronuclei counts in groups decreased with the highest to lowest counts occurring in the order SGP > SHP > NGP > NHP. Gingival micronuclei counts in groups decreased from SGP > SHP > NGP = NHP. The most intense inflammatory cell and vascular densities occurred in SGP and NGP groups, respectively; and the mildest values were in healthy periodontium groups. Histopathological damage score decreased significantly by group in order SGP > NGP > SHP > NHP. The synergy arising from the combination of smoking and periodontitis exposures exacerbates genotoxic and histopathologic damage in oral cells and the periodontium.

Vitamin C elicits protection against cylophosphamide-induced nephrotoxicity in rat animal model

Background: Cyclophosphamide (CPD) causes renal cell toxicity due to its toxic metabolites. Objectives: This study aimed to evaluate the nephroprotective effect of vitamin C at 125 mg/kgBW, 250 mg/kgBW, and 500 mg/kgBW doses based on the biomarker level of urea, creatinine, parameter of urinalysis and renal histopathology. Material and Methods: The experimental animals consisted of 25 rats (Rattus norvegicus) that were divided into 5 treatment groups: healthy control, placebo (water for injection + CPD 250mg/kgBB), and 3 vitamin C treatment groups (125, 250, or 500 mg/kgBW + CPD 250mg/kgBB). Results: The results of blood biomarker, urine analysis, and histopathological analysis showed that CPD induced nephrotoxicity characterized by an increase in urea levels from 21.79 mg/l to 156.65 mg/l, creatinine from 0.375 to 0.717 mg/l, urine protein from 0 to 2.7, with histopathological damage scores from mild to severe (scores 1-3). In the treatment groups, the average damage score was 1-2 (mild score). However, of the three doses used, only the 500 mg/kg dose had significantly improved biomarkers compared to the placebo group, including the urea, creatinine, and urine protein levels, as well as histopathological scores (p&lt;0.05). Conclusions: Vitamin C at a dose of 250 mg/kgBW was able to prevent the increase of urea, creatinine, and urine protein levels, however, a higher dose (500 mg/kg) was required to provide optimal protection against renal structural damage caused by cyclophosphamide.

TIMP-2 and IGFBP7 in human kidney biopsies in renal disease.

Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are markers of tubular stress and urinary [TIMP-2]*[IGFBP7] is an established biomarker for risk assessment of acute kidney injury. There are no studies of expression profiles or localization of these markers in human renal tissue with confirmed renal disease. We analysed 37 kidney biopsies of patients with renal disease and 10 non-diseased control biopsies for TIMP-2 and IGFBP7 expression using immunohistochemistry. Changes in glomerular morphology were evaluated by a semi-quantitative glomerulosclerosis score (GSI) and tubular interstitial changes were graded by the tubular injury score (TSI) using periodic acid-Schiff-stained paraffin sections. Interstitial fibrosis and tubular atrophy (IF/TA) were graded according to the Banff classification. Urinary [TIMP-2]*[IGFBP7] was collected at the time of biopsy. TIMP-2 and IGFBP7 had significantly greater expression in kidney biopsies from patients with renal disease compared with control tissue, especially in the tubular compartment. Here, IGFBP7 was detected in proximal and distal tubules while TIMP-2 was predominantly localized in the collecting ducts. Renal injury significantly correlated with staining intensity for TIMP-2 and IGFBP7: GSI weakly correlated with glomerular TIMP-2 (r=0.36) and IGFBP7 (r=0.35) and TSI correlated with tubular TIMP-2 (r=0.41) and IGFBP7 (r=0.43). Urinary [TIMP-2]*[IGFBP7] correlated weakly with the histopathological damage score but not with glomerular and tubular expression. Our findings underline the role of TIMP-2/IGFBP7 as an unspecific marker of renal injury that is already in use for early detection of acute kidney injury.

The effect of combining basil seeds and gum Arabic on the healing process of experimental acetic acid-induced ulcerative colitis in rats

Background & aimUlcerative colitis (UC) is a chronic recurrent inflammatory disease of the large intestine and rectum that oxidative stress and severe inflammation are the main features of this disease. Previous studies have shown that separate consumption of basil and gum arabic can reduce inflammation and oxidative stress. The aim of the study was evaluating the effect of treatment with basil seeds given together with gum arabic on healing, inflammation and oxidative stress in the course of experimental colitis in rats. Experimental procedureA total number of 50 male rats were used, randomly assigned to five groups of 10 rats each. Colitis was induced in rats by enemas with 4% solution od acetic acid. Four days after induction of colitis, rats were treated for next 4 days with saline or combination of basil seeds plus gum arabic (1 mg/kg) or sulfasalazine (100 mg/g) rectally. The experiment was terminated after last dose of treatment. Rats without induction of colitis were used as a sham group. ResultsAcetic acid-induced colitis increased the macroscopic and histopathological damage scores of the colon as well as colon levels of MDA(Malondialdehyde), MPO(Myeloperoxidase), TNFα(Tissue necrosis factor α), IL6 (Interleukin 6)and IL17(Interleukin 17) and decreased SOD(Superoxide Dismutase), GPx (Glutathione Peroxidase) and IL10 (Interleukin 10) levels compared with the control group(P < 0.001). Treatment with basil and gum arabic reduced macroscopic and histopathological damage scores (P < 0.01) of the colon, MDA, MPO, TNFα, IL6(P < 0.001) and IL17 (P < 0.01) levels of the colon and increased SOD, GPx and IL10 levels compared to the colitis group (P < 0.01). ConclusionRectal administration of combination of basil seeds plus gum arabic after induction of colitis, exhibits antioxidant and anti-inflammatory effects, and accelerates the healing of the colon in experimental colitis evoked by acetic acid.