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In recent decades, chemotherapy has significantly improved cancer survival, yet its adverse effects on non-cancerous tissues raise increasing concerns. In this context, growing attention has been focused on natural compounds that may be useful in mitigating the undesirable effects of chemotherapeutic agents. Here, we aimed to demonstrate that Cytosporone B (CsnB) is a potent agent for counteracting the cardiovascular effects induced by Imatinib. To this end, 12-week-old male Wistar rats were studied; they were divided into three groups as follows: (1) control, (2) Imatinib-treated (Imatinib: 60 mg/kg/day, per os), (3) Imatinib + CsnB-treated (CsnB: 5 mg/kg/day, i.p.). After the two-week-long experimental period, rats were euthanized. Their hearts were used for the following biochemical measurements: NADPH oxidase (NOX4), high mobility group box 1 (HMGB1), peptidylarginine deiminase 4 (PAD4), inducible nitric oxide synthase (iNOS) expression, tumor necrosis factor-alpha (TNF-α) level, and myeloperoxidase (MPO) activity. Imatinib caused a marked upregulation of key inflammatory and oxidative markers, including HMGB1, TNF-α, MPO, iNOS, PAD4, and NOX4 in cardiac tissue; however, CsnB treatment mitigated these elevations, implying its role in opposing Imatinib-induced inflammatory and oxidative processes in the heart. Our findings suggest that CsnB holds promise as a cardioprotective agent capable of modulating Imatinib-induced adverse cardiac effects.

Several substances with antioxidant and anti-inflammatory properties are currently being investigated as potential adjunctive or standalone treatments for inflammatory bowel disease (IBD). One such substance is resveratrol (RES), also known as 3,5,4′-trihydroxy-trans-stilbene, a natural dietary polyphenol with diverse health-promoting effects. In this study, male Wistar–Hannover rats received oral RES supplementation at doses of 5, 10, or 20 mg/kg/day for 28 days. On day 25 colitis was induced using intracolonic administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Based on histological and planimetric analysis, the 10 mg/kg dose significantly reduced colonic ulceration and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) expression compared to the TNBS group. Immunohistochemistry also revealed that RES at this dose attenuated the intensity of TNF-α receptors, namely TNFR1 and TNFR2. Furthermore, the concentration of lipocalin-2 (Lcn-2) was significantly elevated in TNBS-induced colitis. In conclusion, our findings suggest that RES may exert its protective effects partly through the modulation of TNF receptor signaling in TNBS-induced colitis.

BGP-15, a poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor exerts cardioprotective effects; however, the underlying mechanisms remain unclear. Therefore, our study aimed to investigate the effects of BGP-15 on the imatinib (Imtb)-induced cardiac inflammation at the biochemical level. Male rats were divided to control, Imtb-treated (60 mg/kg/day for 14 days), and Imtb + BGP-15-treated animals. In this group Imtb was co-administered with BGP-15 at the dose of 10 mg/kg/day. At the end of the experiment, nuclear factor-kappa B/p65 (NF-κB/p65), nuclear transcription factor erythroid-2 related factor (Nrf2), heme oxygenase-1 (HO-1), high mobility group box 1 (HMGB1), and myeloperoxidase (MPO) were measured by Western blot. Chemokine and interleukins (ILs) were determined by Legendplex. Additionally, cardiac specific changes were visualized by immunohistochemistry. We demonstrated that Imtb increased NF-κB/p65, IL-6, IL-1β, IL-18, MCP-1, HMGB1, as well as the expression and activity of MPO. Conversely, the expressions of antioxidant Nrf2 and HO-1 were decreased. Administration of BGP-15 effectively mitigated these inflammatory alterations by significantly reducing pro-inflammatory cytokines and MPO activity, while simultaneously restoring and enhancing the levels of Nrf2 and HO-1, thereby promoting antioxidant defenses. The immunohistochemical staining further supported these biochemical changes. Our study provides new and comprehensive biochemical insight for managing Imtb-induced inflammatory responses via BGP-15-induced PARP1 inhibition.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral anti-diabetic drugs, implicated in pleiotropic secondary cardioprotective effects. The aim of the study was to unveil the unknown and possible cardioprotective targets that can be exerted by sitagliptin (Sitg) against ischemia-reperfusion (I/R) injury. Male wistar rats received 2 weeks? Sitg oral treatment of different doses (25, 50, 100, and 150 mg/kg/day), or saline as a Control. Hearts were then isolated and subjected to two different I/R injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for infarct size (IS) measurement, or: 10 min perfusion, 45 min regional ischemia and 10 min reperfusion for biochemical analysis: nitric oxide synthases (NOSs) and DPP-4 activity, glucagon-like peptide-1 (GLP-1), Calcium, transient receptor potential vanilloid (TRPV)-1 and calcitonin gene-related peptide (CGRP) levels, transient receptor potential canonical (TRPC)-1 and e-NOS protein expression. NOS inhibitor (L-NAME) and TRPV-1 inhibitor (Capsazepine) were utilized to confirm the implication of both signaling mechanisms in DPP-4 inhibition-induced at the level of IS. Findings show that Sitg (50 mg) resulted in significant decrease in IS and DPP-4 activity, and significant increase in GLP-1, NOS activity, e-NOS expression, TRPV-1 level and TRPC-1 expression, compared to controls. Results of CGRP are in line with TRPV-1, as a downstream regulatory effect. NOS system and transient receptor potential (TRP) channels can contribute to DPP-4 inhibition-mediated cardioprotection against I/R injury using Sitagliptin.

The global burden of cardiovascular diseases is indisputable, as it claims nearly 18 million lives a year. In this current study, we aimed to prove that exercise, a cornerstone in cardiovascular disease management, emerges as a powerful tool in the pathology of myocardial ischemia. Male rats were divided into three groups: pre-swimming training + isoproterenol (ISO) treated, isoproterenol-treated, and control-sedentary. Myocardial infarction was induced by the subcutaneous injection of 1.0 mg/kg ISO. After the subsequent rest period, the animals swam for 3 weeks, every day for 25 min. At the end of the experiment, the serum levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as well as the cardiac concentrations of reactive oxygen species (ROS), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined. Our results indicate that both cardiac injury biomarkers (ANP, BNP) and ROS levels were significantly lower in swimming rats compared to the sedentary animals. Moreover, the level of enzymatic components of the intracellular antioxidant system, CAT, SOD, and GPx were increased in swimming animals after ISO-induced myocardial infarction. Our findings support the fact that moderate-intensity swimming training can be efficiently used to prevent myocardial infarction-induced ischemic injury, by inhibiting ROS production and strengthening intracellular antioxidant defense.

Although the morphological features and functions of adipose tissue are well-described in obesity-prone animal models, less information is available on animals such as the stroke-prone spontaneously hypertensive (SHRSP) strain with cardiovascular abnormalities, which is not characterized by excessive adiposity. Our aim was to focus on lifestyle-induced (type of diet and physical exercise) effects on adipokine profile and lipid peroxidation in SHRSP rats. In our study, male Wistar-kyoto (control) and SHRSP rats were used. SHRSP rats were fed either standard chow or a high-fat diet with 40% fat content (HFD). One group of the animals was placed into cages fitted with a running-wheel; thus, the dietary and training period started at the same time and lasted for 12 weeks. At the end of the experimental period, adiponectin, leptin, omentin, and chemerin concentrations were determined from adipose tissue and serum. Besides adipokines, malondialdehyde (MDA) levels were also measured. Twelve weeks of HFD significantly decreased adiponectin and omentin concentrations of both adipose tissue and serum, which were ameliorated by physical exercise. Serum leptin, chemerin, and MDA values were elevated in HFD groups; however, physical exercise was able to mitigate these adverse changes. Our results underpin the crosstalk between lifestyle changes and dysfunctional adipose tissue in SHRSP rats.

Inflammatory bowel diseases (IBD) are chronic, immune-mediated disorders, which affect the gastrointestinal tract with intermittent ulceration. It is increasingly clear that neutrophil extracellular traps (NETs) seem to have a role in IBD; however, the associated pathogenesis is still not known. Furthermore, several conventional therapies are available against IBD, although these might have side effects. Our current study aimed to investigate the effects of hydrogen sulfide (H2S) treatment on NETs formation and on the expression of inflammatory mediators in experimental rat colitis. To model IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was administered intracolonically (i.c.) to Wistar–Harlan male rats. Animals were treated (2 times/day) with H2S donor Lawesson’s reagent per os. Our results showed that H2S treatment significantly decreased the extent of colonic lesions. Furthermore, the expression of members of NETs formation: peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (citH3), myeloperoxidase (MPO) and inflammatory regulators, such as nuclear transcription factor-kappa B (NF-κB) and high-mobility group box 1 (HMGB1) were reduced in H2S treated group compared to TNBS. Additionally, H2S donor administration elevated the expression of ubiquitin C-terminal hydroxylase L1 (UCHL-1), a potential anti-inflammatory mediator. Taken together, our results showed that H2S may exert anti-inflammatory effect through the inhibition of NETs formation, which suggests a new therapeutic approach against IBD.

Inflammatory bowel diseases (IBD) are chronic, inflammatory disorders of the gastrointestinal (GI) system, which have become a global disease over the past few decades. It has become increasingly clear that oxidative stress plays a role in the pathogenesis of IBD. Even though several effective therapies exist against IBD, these might have serious side effects. It has been proposed that hydrogen sulfide (H2S), as a novel gasotransmitter, has several physiological and pathological effects on the body. Our present study aimed to investigate the effects of H2S administration on antioxidant molecules in experimental rat colitis. As a model of IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used intracolonically (i.c.) to induce colitis in male Wistar–Hannover rats. Animals were orally treated (2 times/day) with H2S donor Lawesson’s reagent (LR). Our results showed that H2S administration significantly decreased the severity of inflammation in the colons. Furthermore, LR significantly suppressed the level of oxidative stress marker 3-nitrotyrosine (3-NT) and caused a significant elevation in the levels of antioxidant GSH, Prdx1, Prdx6, and the activity of SOD compared to TNBS. In conclusion, our results suggest that these antioxidants may offer potential therapeutic targets and H2S treatment through the activation of antioxidant defense mechanisms and may provide a promising strategy against IBD.

Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar–Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.

Inflammatory bowel diseases (IBDs) are autoimmune disorders of the gut. It is increasingly clear that voluntary exercise (VE) may exert protection against IBDs, but the exact background mechanism needs to be elucidated. In the present study, we aimed to investigate the possible role of NETosis and the antioxidant peroxiredoxin (Prdx) enzyme family in VE-induced protection. Wistar Han rats were randomly divided into two groups: sedentary (SED) and VE. After the 6-week voluntary wheel running, animals were treated with 2,4,6-trinitrobenzene sulphonic acid (TNBS) as a model of colitis. Here, we found that VE significantly decreased inflammation and ulceration of the colon in the VE TNBS group compared with SED TNBS. We also found that VE significantly decreased the expression of protein arginine deiminase 4 (PAD4) and myeloperoxidase (MPO), and markedly reduced citrullinated histone H3 (citH3) compared with SED TNBS. Furthermore, VE caused a significant increase in the levels of Prdx6 in the control and TNBS groups. Taken together, we found that a prior 6-week VE effectively reduces inflammation in TNBS-induced colitis, and we suggest that the protective effect of VE may be mediated via the inhibition of NETosis and upregulation of Prdx6 antioxidant.