Gilaburu (Viburnum opulus L.) fruit extract has potential therapeutic and prophylactic role in a rat model of acetic acid-induced oxidant colonic damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied. AIM OF THE STUDY: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC. MATERIALS AND METHODS: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-ß1, smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3rd day. RESULTS: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1ß, IL-6, IL-8), MMP-9, TGF-ß1, smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-ß1 measurements significantly. CONCLUSIONS: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis.

Incidence of Thromboembolism in COVID-19 Patients in Intensive Care Units: A Retrospective Cohort Analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection was declared a pandemic, causing high mortality and morbidity worldwide. It predisposes patients to both arterial and venous thromboembolism, which causes high mortality, and is one of the most serious complications of the disease. OBJECTIVE: The aim of this retrospective study was to determine the frequency of thromboembolic events in patients diagnosed with COVID-19 in the intensive care unit (ICU) and to identify the factors causing thromboembolism. MATERIAL AND METHODS: The digital records of patients admitted to the adult ICU of Derince Training and Research Hospital, Kocaeli, Turkey, with a diagnosis of COVID-19 between March 13, 2020, and December 31, 2021, were retrospectively reviewed. RESULTS: Data of 484 patients, 248 (51.2%) female and 236 (48.8%) male, aged between 18-98 years were analyzed. The overall, arterial and venous incidence of thromboembolism was 14.8%, 11.3%, and 3.5%, respectively. There was no significant association between COVID-19 variants and the development of thromboembolism. The effect of various patient variables on the development of thromboembolism was evaluated, including cardiovascular disease (p<0.001), age (p=0.003), use of acetylsalicylic acid (ASA) (p<0.001), antiplatelet therapy (p<0. 001), acute physiology and chronic health evaluation (APACHE) II score (p=0.003), D-dimer (p=0.015), fibrinogen (p=0.032), ferritin (p=0.015), prothrombin time (PT) (p=0.015), international normalized ratio (INR) (p=0.012), troponin (p=0.012) values at the ICU admission were found statistically significant. The cut-off values were 2.565 (µg/mL) for D-dimer, 435.51 (mg) for fibrinogen, 633.55 (ml/ng) for ferritin, 1.155 for INR, and 0.085 (ng/mL) for troponin. CONCLUSION:  Although low-molecular-weight heparin (LMWH) is the first choice, it may be appropriate to add ASA and other antiplatelet agents to reduce the risk of thromboembolism in patients with high thromboembolic risk including advanced age, cardiovascular disease, and elevated levels of D-dimer, troponin, ferritin, and fibrinogen.

Investigation of Eating Habits in Patients with Functional Dyspepsia.

BACKGROUND: Nutritional habits of patients with functional dyspepsia can affect the progression of functional dyspepsia. We aimed to determine the foods and dietary habits that may cause symptoms of postprandial fullness, early satiety, epigastric pain, and epigastric burning in functional dyspepsia patients. METHODS: Sixty functional dyspepsia patients, who were diagnosed according to Rome IV criteria in the endoscopy unit of a gastroenterology institute, were included in the study. Data on the demographic characteristics, anthropometric measurements, nutritional habits, and food consumption frequency questionnaire of functional dyspepsia patients were collected. RESULTS: Postprandial fullness was found more common in those who preferred roasting as a cooking method. There was no significant difference between symptoms and meal frequency. Epigastric burning and pain were found to be more pronounced in women, and alcohol consumption was less in patients who experienced more epigastric pain. In non-smoker participants, the complaint of early satiety was lower. It was found that broccoli, radish, celery, green olives, and olive oil consumption was less in participants who experienced excessive postprandial fullness. Patients with stomach pain consumed less dry fruits, green olives, butter, alcohol, and fast food. It was found that patients with stomach burning consumed less alcohol and fast food. CONCLUSION: In conclusion, functional dyspepsia patients should avoid or reduce consuming broccoli, radish, celery, green olives, olive oil, dry fruits, and butter which may trigger symptoms. Reducing consumption of these foods, abandoning unhealthy cooking methods such as roasting, reducing smoking, and reducing consumption of alcohol and fast food might be beneficial for relieving symptoms.

Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes

Abstract Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.

Halofuginone improves caustic-induced oxidative injury of esophagus in rats.

BACKGROUND: The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats. MATERIALS AND METHODS: Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity. RESULTS: GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone. CONCLUSION: In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats.

Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-ß1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

Halofuginone Alleviates Burn-Induced Hepatic and Renal Damage in Rats.

The aim of this study was to evaluate the possible protective effects of halofuginone on burn-induced oxidative injury of the liver and kidney. For the induction of burn, backs of Wistar albino rats were shaved and exposed for 10 seconds to water bath at 90°C, whereas rats in the control group were exposed for 10 seconds at 25°C. Rats were then administered either saline (1 ml/kg) or halofuginone (100 µg/kg/day) intraperitoneally and decapitated at the 24th hour (early burn) or on the 7th day (late burn). Serum concentrations of creatinine, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase were determined. Renal and hepatic tissue samples were used for microscopic analysis, and glutathione, malondialdehyde, and myeloperoxidase activity and chemiluminescence levels were measured. Halofuginone treatment improved renal functions in late burn group and hepatic functions in early burn group as demonstrated by decreased serum creatinine, blood urea nitrogen, and alanine aminotransferase levels. Increased serum lactate dehydrogenase level measured in late phase was reduced by halofuginone treatment. Generation of reactive oxygen metabolites measured by chemiluminescence, indicating burn-induced renal and hepatic oxidative injury in both the early and late burn groups, was reduced by halofuginone. Increased hepatic malondialdehyde levels accompanied with high microscopic damage scores were reversed by halofuginone in early burn group, while depleted renal glutathione levels were replenished. The present findings demonstrate that halofuginone preserved renal and hepatic functions and alleviated oxidative tissue damage insulted by burn trauma, suggesting an anti-inflammatory and antioxidant potential for halofuginone in providing protection against burn-induced renal and hepatic injury.

Treatment with either obestatin or ghrelin attenuates mesenteric ischemia-reperfusion-induced oxidative injury of the ileum and the remote organ lung.

To evaluate the effects of exogenous ghrelin or obestatin on intestinal injury and accompanying pulmonary injury, intestinal ischemia-reperfusion (I/R) was induced in rats by obstructing the superior mesenteric artery for 60min, whereas laparotomy was performed in the sham group. At the beginning of the 90-min reperfusion period, the rats were injected with obestatin (100µg/kg), ghrelin (10ng/kg), or saline intravenously (iv). At the end of reperfusion, the blood, ileum, and lung samples were taken for the histological and biochemical assays. In the saline-treated I/R group, the increased serum interleukin (IL)-1ß level, high damage scores, and elevated tissue malondialdehyde level and collagen content in both tissues were significantly reduced by obestatin or ghrelin. Increased ileal myeloperoxidase activity of the saline-treated I/R group was reduced by treatment with obestatin or ghrelin, whereas increased pulmonary myeloperoxidase activity was reduced with administration of obestatin. Increased DNA fragmentation in the ileum of the saline-treated I/R group was reduced by both peptides. Elevated luminol-lucigenin chemiluminescence levels and nuclear factor kappa B (NF-κB) messenger RNA (mRNA) expression in the ileum of the saline-treated-I/R group were significantly decreased by obestatin or ghrelin treatment. I/R-induced depletion of the antioxidant glutathione in both ileal and pulmonary tissues was prevented with either obestatin or ghrelin treatment. Administration of either obestatin or ghrelin exerts similar protective effects against I/R-induced ileal and pulmonary injury, thus warranting further investigation for their possible use against ischemic intestinal injury.

The antifibrotic drug halofuginone reduces ischemia/reperfusion-induced oxidative renal damage in rats.

AIM: The objective of the present study was to evaluate the protective effects of halofuginone against renal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Wistar albino rats were unilaterally nephrectomized and the left renal pedicles were occluded for 45 min to induce ischemia and then reperfused for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with either halofuginone (100 µg/kg/day) or saline 30 min prior to ischemia and the dose was repeated in the late reperfusion groups. In the sham groups, rats underwent unilateral nephrectomy and were treated at similar time points. The animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and kidney samples were obtained. RESULTS: I/R injury increased renal malondialdehyde levels, myeloperoxidase activity and reactive oxygen radical levels, and decreased the renal glutathione content. Halofuginone treatment was found to reduce oxidative I/R injury and improve renal function in the rat kidney, as evidenced by reduced generation of reactive oxygen species, depressed lipid peroxidation and myeloperoxidase activity, and increased glutathione levels. CONCLUSIONS: The present findings demonstrate the anti-inflammatory and antioxidant effects of halofuginone in renal I/R injury, supporting its potential use where renal I/R injury is inevitable.

The effect of phosphodiesterase-5 inhibition by sildenafil citrate on inflammation and apoptosis in rat experimental colitis.

AIMS: To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant-antioxidant status and apoptosis in rats with colitis. MAIN METHODS: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30 mg/ml; 0.8 ml) given intrarectally to Sprague-Dawley rats. Sildenafil (25 mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7 days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25 mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25 mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays. KEY FINDINGS: The macroscopic lesion score of the colitis group was reduced by SIL (p < 0.01) and this effect was abolished by l-NAME (p < 0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p < 0.01 and p < 0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p < 0.001). Sildenafil also reduced the elevated MPO of the colitis group (p < 0.001) and this effect was reversed by L-NAME (p < 0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p < 0.001 and p < 0.01, respectively). SIGNIFICANCE: Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant-antioxidant status, prevention of apoptosis, superoxide production and cytokine release.

Halofuginone, a specific inhibitor of collagen type 1 synthesis, ameliorates oxidant colonic damage in rats with experimental colitis.

To evaluate the effect of halofuginone on trinitrobenzene sulfonic acid (TNBS)-induced colonic injury, rats were given halofuginone (40 microg/kg, intraperitoneally) or saline 1 h before the induction of colitis, and the injections were continued twice daily for 3 days until they were decapitated. High macroscopic and microscopic damage scores, elevated colonic wet weights, colonic myeloperoxidase activity, malondialdehyde and tissue collagen level, and luminol chemiluminescence values, and marked reduction in glutathione level of the saline-treated colitis group were all reversed by treatment with halofuginone. In conclusion, halofuginone exerts beneficial effects in TNBS-induced colonic inflammation in rats. The anti-inflammatory effects of halofuginone appear to involve suppression of neutrophil accumulation, preservation of endogenous glutathione, and inhibition of reactive oxidant generation. Halofuginone also shows antifibrotic effect via inhibition of tissue collagen production. The present data encourage possible use of the antifibrotic halofuginone as an anti-inflammatory agent in improving oxidative injury in colitis.

Halofuginone has a beneficial effect on gentamicin-induced acute nephrotoxicity in rats.

The aim of this study was to investigate the putative beneficial effect of halofuginone on gentamicin-induced nephrotoxicity in rats. Sprague-Dawley rats were treated with gentamicin sulphate (GEN; 80 mg/kg) or saline intraperitoneally (i.p.) for 7 days. Halofuginone was administered (0.1 mg/kg/day; i.p.) following GEN or saline injections. Blood and urine samples were collected to measure the renal function tests. Kidneys were excised for histological evaluation and for the measurement of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, and chemiluminescence (CL). Halofuginone treatment to animals with GEN-induced renal injury caused a significant decrease in serum blood urea nitrogen level and reduced the elevated MDA, GSH content, and MPO activity. It was also effective in reversing the elevated CL values of rats with GEN-induced nephrotoxicity and preserving renal morphology, as examined microscopically. In conclusion, halofuginone was beneficial in GEN-induced acute nephrotoxicity. The mechanism could be attributed, at least in part, to decreased tissue leukocyte infiltration and reactive metabolite production.

Alpha-lipoic acid improves acetic acid-induced gastric ulcer healing in rats.

To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.

Serum prolidase and IGF-1 as non-invasive markers of hepatic fibrosis during four different periods after bile-duct ligation in rats.

AIM: Our aim was to study the correlation of serum prolidase and insulin like growth factor-1 to liver collagen and assess their utility as markers of fibrosis during four different periods of hepatic injury and fibrosis after bile-duct ligation in rats. METHODS: Forty-eight Wistar albino rats were included in the study and divided into six groups. Seven rats served as the control group (Control), while seven rats had a sham operation (Sham group). Thirty-four rats underwent bile-duct ligation. Bile-duct ligated (BDL) animals were sacrificed at the end of the first week (Group 1; n = 8), second week (Group 2; n = 8), third week (Group 3; n = 9), or fourth week (Group 4; n = 9) after BDL. Liver collagen, liver prolidase, and serum prolidase and IGF-I, were determined. RESULTS: There was a positive correlation between liver collagen and serum prolidase (r(s): 0.843, P < 0.001) levels and a negative correlation among liver collagen and serum IGF-1 levels (r(s): -0.667, P < 0.001). The peak levels of liver collagen and serum prolidase were reached in the third week while the lowest levels of IGF-1 were found at the end of the third week. CONCLUSION: Serum prolidase and IGF-1 either independently or in combination correlate with liver collagen content in hepatic fibrosis.