ABSTRACT
BACKGROUND AND PURPOSE: Cancer is the primary cause of death in the world. Vanadium (IV) is a metal ion complex which has been proposed as a suitable candidate for cancer treatment. In this study, the interaction of the oxido-vanadium (IV) complex [VOL(bipy)] with salmon sperm DNA and Bovine Serum Albumin (BSA) was investigated through experimental and computational approaches. With the results of this experimental study, the mechanism and parameters related to the interaction of [VOL(bipy)] with DNA and BSA were determined. MATERIALS AND METHODS: The kinetic interaction of DNA and BSA with [VOL(bipy)] was determined using absorption titration and fluorescence quenching, respectively. Moreover, the possible interactions were calculated by molecular docking prediction using the available software. RESULTS: The binding constant (Kb) of the complex-DNA interaction was calculated to be 2.34×104 M-1, indicating a relatively strong interaction between the complex and DNA. It was found that the V(IV) complex interacted with DNA through the groove binding mode followed by partial intercalation into the DNA helix. The Kb values obtained for [VOL(bipy)]-BSA interaction were in the range of 1.07×103-5.82×104 M-1. The V(IV) complex was found to prefer the domain I binding pocket of BSA with the ΔGb value of -7.52 kcal/mol. CONCLUSION: Both experimental and computational analyses confirmed the interaction of the vanadium complex with DNA and BSA. The moderate affinity of [VOL(bipy)] for BSA indicates that this protein is a good candidate for transferring the complex.
Subject(s)
Antineoplastic Agents/chemistry , Coordination Complexes/chemistry , DNA, Neoplasm/chemistry , Schiff Bases/chemistry , Serum Albumin, Bovine/chemistry , Vanadates/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Cattle , Coordination Complexes/chemical synthesis , Humans , Kinetics , Molecular StructureABSTRACT
The aim of this study was to investigate effects of troxerutin (TRX) on endurance capacity, oxidative stress and matrix metalloproteinase-9 (MMP-9) levels in trained male rats. Forty male Wistar rats were divided into five groups. The control (Vehicle) and exercise training (5 days/week) with vehicle treatment (Exercise), exercise training with TRX treatment at 75 (Ex-TRX75), 150 (Ex-TRX150), and 300 mg/kg (Ex-TRX300). The treated groups received TRX by gavage every day while the other groups received water for 30 days. On the 30th day, rats were sacrificed immediately after exhaustive swimming test, and some biochemical parameters were measured. Exhaustion swimming time in the Ex-TRX75, Ex-TRX150 and Ex-TRX300 groups significantly increased 1.2-, 1.93- and 2.1-fold compared to the vehicle group, respectively. TRX significantly increased glucose level (P < 0.05) and reduced creatine kinase activity (P < 0.001) compared to the vehicle and exercise groups. TRX300 significantly reduced alkaline phosphatase and lactate dehydrogenase activities (P < 0.05) and blood urea nitrogen (P < 0.05) and MMP-9 levels (P < 0.05) compared to the vehicle and exercise groups. Additionally, TRX300 and TRX150 significantly increased superoxide dismutase activity compared to the vehicle group (P < 0.05). Our results provide experimental evidence in supporting clinical use of TRX as an effective agent against fatigue.
Subject(s)
Hydroxyethylrutoside/analogs & derivatives , Matrix Metalloproteinase 9/blood , Muscle Fatigue/physiology , Oxidative Stress/physiology , Physical Conditioning, Animal/physiology , Physical Endurance/physiology , Animals , Anticoagulants/pharmacology , Dose-Response Relationship, Drug , Hydroxyethylrutoside/pharmacology , Male , Muscle Fatigue/drug effects , Oxidative Stress/drug effects , Physical Conditioning, Animal/methods , Physical Endurance/drug effects , Rats , Rats, Wistar , Swimming/physiologyABSTRACT
Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke.
