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OBJECTIVES: The aim of the study is to examine the effect of Ambroxol on TNF-α and IL-1β released after liver ischemia-reperfusion injury. BACKGROUND: Many drugs are being tried to reduce ischemia-reperfusion injury, which is life threating problem after many liver surgeries. In this study, it was investigated whether Ambroxol reduces the release of pro-inflammatory cytokines released after liver ischemia-reperfusion injury. METHODS: Twenty-four Wistar albino rats were divided into 3 groups as Control (CTR; n=8), hepatic ischemia reperfusion (H-IR; n=8) and hepatic ischemia reperfusion+Ambroxol (H-IR+AMB; n=8). In H-IR+AMB group, Ambroxol (30 mg/kg) was administered orally 30 minutes before ischemia period. In H-IR and H-IR+AMB groups underwent 45 minutes of hepatic ischemia followed by a 60-minute reperfusion period. After reperfusion period, tissue and blood samples were collected from euthanised animals. ALT, AST, ALP, LDH, TNF-α, IL-1β concentrations and liver tissues were evaluated. RESULTS: Serum ALT, ALP, AST, LDH, TNF-α and IL-1β values were lower in the H-IR+AMB group compared to the H-IR group. In the histopathological examination, hepatocyte degeneration and congestion in the H-IR group were higher than in the H-IR+AMB group. CONCLUSION: It was determined that Ambroxol treatment suppressed the production of pro-infl ammatory cytokines TNF-α and IL-1β in rats undergoing hepatic ischemia reperfusion (Tab. 1, Fig. 2, Ref. 28). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]

Objective: Agmatine, the decarboxylation product of arginine produced by arginine decarboxylase, is a novel neurotransmitter and exists in the mammalian brain. Agmatine has been reported to modulate cognitive functions, including learning and memory. Methods: In the present study, we evaluated the effects of agmatine on cognitive performance and oxidative damage in intracerebroventricular (i.c.v.) streptozotocin (STZ) model of Alzheimer's disease (AD). Adult male Sprague-Dawley rats were injected STZ (3mg/kg, i.c.v, bilaterally) on days 1 and 3. The learning and memory patterns were assessed by using passive avoidance, Morris water maze, and closed field activity tests. Also, malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity have been determined as the parameters of oxidative damage. The behavioral tests were performed after 14 days from the first injection of STZ. Rats with impaired learning and memory performance were treated with intraperitoneal (i.p.) agmatine (40 mg/kg) twice daily for 7 days. After agmatine treatment, rats were subjected to the aforementioned behavioral tests again. Immediately after decapitation of the rats, the brains were collected and analyzed for oxidative damage parameters. Results: Agmatine improved the STZ-induced both spatial and emotinal memory impairment and oxidative damage. Findings of the study demonstrated the effectiveness of agmatine in reversing the cognitive deficits as well as the oxidative damage caused by i.c.v STZ. Conclusion: Taken together, our results have provided experimental evidence suggesting a possible therapeutic potential of agmatine as a regulator in etiopathogenesis of neurodegenerative diseases such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Oxidative stress, in particular lipid peroxidation, induces collagen synthesis and causes fibrosis. The aim of this study was to assess the antioxidant and antifibrotic effects of erdosteine on liver fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in Wistar albino rats by bile duct ligation (BDL). Erdosteine (10 mg/kg, orally) or saline was administered for 28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were determined to assess liver functions and tissue damage, respectively. Pro-inflammatory cytokines, TNF-α, IL-1β and IL-6 and antioxidant capacity (AOC) were assayed in plasma samples. Liver tissues were taken for determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH, and plasma cytokines were elevated in the BDL group as compared to controls and were significantly decreased by erdosteine treatment. Hepatic GSH level and plasma AOC, depressed by BDL, were elevated back to control level with erdosteine treatment. Furthermore, hepatic luminol and lucigenin chemiluminescence (CL), MDA level, MPO activity and collagen content in BDL group increased dramatically compared to control and reduced by erdosteine treatment. Since erdosteine administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that erdosteine with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. [ABSTRACT FROM AUTHOR]

Provides information on a study that determined whether melatonin protects the rat bladder against contractile dysfunction and oxidative damage induced by reperfusion of the urinary tract followed by abdominal aorta ligation. Methodology of the study; Results and discussion on the study.

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases. [ABSTRACT FROM AUTHOR]

Chronobiology, which studies biological rhythms and their impacts on health, presents a potential avenue for treating amyotrophic lateral sclerosis. Clock gene-related therapies, focusing on genes responsible for regulating biological rhythms, may hold promise in the treatment. Among these clock genes, nuclear receptor subfamily 1 Group D member 1 (NR1D1) plays a vital role in neurodegenerative diseases. In this particular study, it was aimed to investigate the potential of FDA-approved drugs commonly used in amyotrophic lateral sclerosis treatment and melatonin, a hormone known for its role in regulating sleep-wake cycles, as ligands for clock gene-related therapy. The ligands were subjected to molecular docking and molecular dynamics simulation methods against the NR1D1 clock gene. These results suggested that combining melatonin with FDA-approved medications commonly used in the treatment might yield positive outcomes. This study provides preliminary data and lays the groundwork for future investigations involving in vitro (laboratory-based) and in vivo (animal or human-based) research on chronotherapy. In summary, this research highlights the potential of clock gene-related therapy utilizing melatonin in conjunction with FDA-approved drugs for amyotrophic lateral sclerosis treatment, offering insights into novel treatment strategies. The findings underscore the need for further studies to explore the effectiveness of this hypothetical approach in experimental and clinical settings. [ABSTRACT FROM AUTHOR]

Activation of pro-inflamatuar pathways play major role in formation of major complications as a result of burns. This study was planned to investigate the protective effect of Silk Fibroin in lung injury caused by burn in the experimental rat model. After rinsing the skin of rats under ether anesthesia, the exposed back region, covers 30% of the total body, was kept in the 90 °C water bath for 10 s. The control rats were kept in the 25 °C water bath for 10 s. Immediately after burning process, silk fibroin was administered orally at a dose of 600 mg/kg. After 24 h following burning from all groups the levels of TNF-α, IL-1β in blood samples and the MDA, GSH and the activity of MPO were determined from taken lung tissues. Moreover, the expression of Bcl-2/Bax, Caspase-3 and Caspase-9 were determined. Significant increase in TNF-α, IL-1β, Casp-3 and Casp-9 levels were observed in the Silk Fibroin-treated burn group ( p < 0.05) whereas for ratio of Bcl-2/Bax, a significant reduction was observed compared to control group ( p < 0.05). Increased levels of TNF-α, IL-1β, Caspase-3 and Caspase-9 in Silk Fibroin-treated burn groups were found to be reversed. Silk fibroin can be an effective biomaterial in diminishing burn injury in tissue and apoptosis. [ABSTRACT FROM AUTHOR]

In this study, we aimed to determine the protective effect of grape seed extract against mesenteric ischemia/reperfusion (I/R) injury in rats. In addition, an in silico molecular docking study was performed to compare the effects of natural compounds in grape seed extract on myeloperoxidase (MPO) enzyme at the molecular level. In addition to MPO activity, malondialdehyde (MDA) and glutathione (GSH) activities were also measured in the intestinal tissue samples. Serum cytokines, TNF-a and IL-1ß, were measured to assess systemic tissue damage. Mesenteric GSH decreased significantly after ischemia/reperfusion, while MDA levels and MPO activity increased significantly. Binding interactions were detected by the binding mode of analysis, and the study compared the binding affinities of compounds at the active site of myeloperoxidase and glutathione peroxidase. As a result, it was found that procyanidins (B1-B4), which are predominantly present in GS extract, have the highest binding affinity and molecular interaction. [ABSTRACT FROM AUTHOR]

With the ongoing pandemic declared by the World Health Organization, the number of hospitalizations and deaths caused by COVID-19 is increasing dramatically. As new variants of SARS-CoV-2 emerge, new combination therapies are needed to reduce the risk of COVID-19spreadduring this time of increased transmission risk. In this case, it is vitalto strengthen the immune system against highly inflammatory conditions such as the cytokine storm caused by COVID-19. This brief review highlights the benefits of taking melatonin and the new antiviral drug molnupiravir together in the treatment of COVID-19. Webelieve that this combination therapy against COVID-19 would be of great benefit and should be considered as an adjuvant therapy in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Aim: Reactive oxygen species play an important role in the pathophysiology of intestinal ischemia/reperfusion (I/R) injury by causing apoptosis. The present study aimed at exploring the possible protective effect of Saint John’s Wort (SJW) extract in I/R injury. Materials and Methods: Twenty four healthy male Wistar rats of 6 to 8 weeks old weighting averagely 200 to 250 g were studied. They were fed on standard rat food and drinking water at room temperature with 12/12 hours periods of day and night. SJW (300 mg/kg, peroral) or saline was given by oral route for 3 days prior to ischemia, 30 minutes before the ischemia, and just before reperfusion. To the rats in the control group, sham operation and application of saline were done. Levels of TNF-α, IL-1β and LDH were measured in the serum samples. In the small bowel tissue, levels of malonaldehyde (MDA) and glutathione (GSH) and activity of myeloperoxidase (MPO) and Na-K ATPase and level of caspase-3/β-actine and Bcl-2/β-actine were measured. Results: I/R increased serum levels of LDH, TNF-α and IL-1β, small bowel level of MDA and MPO whereas it decreased level of GSH and activity of Na-K ATPase in the small bowel tissue. The level of caspase-3/β-actine increased while the level of Bcl-2/β-actine decreased in the I/R group compared to the controls. With the application of SJW, these values approached the control levels. Conclusion: These results indicate that SJW recovers small bowel function by reducing oxidation injury during I/R. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the efficacy of tadalafil against pentoxifylline in rat model of ischemic colitis (IC). Material-Methods: Thirty-two Wistar albino rats were subjected to laparotomy and left colon devascularization to create an IC model and then randomly placed into four groups. Group-1 (sham group) was administered 0.9% NaCl following laparotomy, group 2 (control group) was administered 0.9% NaCl following induced IC, group 3 was given pentoxifylline ( n = 8), and group 4 was given tadalafil. On the third day; macroscopic findings, Gomella's ischemic area and Wallace scoring, histopathological analysis, and Chiu scoring were performed, and malondialdehyde (MDA) measurement in ischemic colon tissue was carried out through chemical analysis. Results: Significant differences were observed in acidic fluid, bowel dilatation, and serosal change ( p < .05). The ischemic area measured 63.3 mm2 in the control group, 2.8 mm2 in the pentoxifylline group ( p = .0001), and 2.4 mm2 ( p = .0001) in the tadalafil group. A significant difference was seen between the sham group and the control and pentoxifylline groups ( p < .01), in terms of Wallace score and Chiu classification. Similarly, a significant difference was determined between the control group and pentoxifylline and tadalafil groups ( p < .01), but no significant difference was established between the pentoxifylline group and tadalafil group ( p = .33). MDA measurement was found on an average to be 63.7 in the control group, 22.7 in group 3 and 22.8 in group 4 ( p = 001). Conclusion: Although tadalafil is superior to pentoxifylline, both drugs are considered to have positive effects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril. Methods: Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90 °C (burn) or 25 °C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken, nNOS was studied in brain areas by immunohistochemistry. Results: There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups, nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p < 0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p = 0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p < 0.05). Conclusions: Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of ursodeoxycholic acid (UDCA) on liver regeneration following partial hepatectomy in rats with non-alcoholic fatty liver disease (NAFLD). Methods: UDCA was administered to seven rats (group 1) and physiological saline was administered both to seven rats (group 2) with NAFLD and to seven rats with normal livers (group 3). All rats underwent two-thirds hepatectomy and the remnant liver tissues were removed 48 h later. Mitotic index (MI) and levels of proliferating cell nuclear antigen (PCNA), glutathione (GSH) and malondialdehyde (MDA) were assayed. Results: MI and PCNA levels in group 2 were significantly lower than in groups 1 and 3, but the values in groups 1 and 3 were similar. The GSH levels of group 2 were significantly lower than those of group 3 in the hepatectomy tissues, and lower than those of groups 1 and 3 in the remnant tissues. The differences between GSH levels in groups 1 and 3 were not significant. MDA levels in hepatectomy and remnant tissues were significantly higher in group 2 compared to groups 1 and 3; values in groups 1 and 3 were similar. Conclusion: UDCA increases regeneration after partial hepatectomy in rats with NAFLD, possibly due to an attenuating effect on oxidative stress. [ABSTRACT FROM AUTHOR]