The underlying mechanisms of Alzheimer's Disease (AD) are still unclear. It is suggested that poly(ADP-ribose) polymerase-1 (PARP-1) overactivation can cause neuroinflammation and cell death. In this study we searched the effects of nicotinamide (NA), endogenous PARP-1 inhibitor, on oxidative stress, apoptosis, and the regulation of PARP-1 and nuclear factor kappa B (NF-κB) in amyloid beta peptide (1-42) (Aβ(1-42))-induced neurodegeneration. Sprague-Dawley rats were divided into four groups as control, Aβ(1-42), Aβ(1-42) + NA(100 and 500 mg/kg). All groups were stereotaxically injected bilaterally into the hippocampus with Aβ(1-42) or saline. After surgery NA administrations were made intraperitoneally (ip) for 7 days. In order to investigate the effects of Aβ(1-42) and NA, protein carbonyls, lipid peroxidation, reactive oxygen species (ROS) production, glutathione (GSH) levels, activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), mitochondrial function, mRNA and protein levels of PARP-1, NF-κB, p53, Bax, and Bcl-2 were measured in specific brain regions such as cortex and hippocampus. Aβ(1-42) treatment only increased the oxidative stress parameters and caused decline in antioxidant enzyme activities, mitochondrial function, and GSH levels. Also, overexpression of PARP-1, NF-κB, p53, Bax, and the decreased levels of Bcl-2 were observed in Aβ(1-42)-treated group. NA treatments against Aβ(1-42)-upregulated Bcl-2 and downregulated PARP-1, NF-κB, p53, and Bax levels. NA treatments also decreased the oxidative stress parameters and elevated antioxidant enzyme activities, GSH levels, and mitochondrial function against Aβ(1-42) treatment. These data suggest that NA may have a therapeutic potential in neurodegenerative processes due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activity.
BackgroundThe wound healing process is complex and still poorly understood. Sericin is a silk protein synthesized by silk worms (Bombyx mori). The objective of this study was to evaluate in vivo wound healing effects of a sericin-containing gel formulation in an incision wound model in rats.Material/MethodsTwenty-eight Wistar-Albino rats were divided into 4 groups (n=7). No intervention or treatment was applied to the Intact control group. For other groups, a dorsal skin flap (9×3 cm) was drawn and pulled up with sharp dissection. The Sham operated group received no treatment. The Placebo group received placebo gel without sericin applied to the incision area once a day from day 0 to day 9. The Sericin Group 3 received 1% sericin gel applied to the incision area once a day from day 0 to day 9. Hematoxylin and eosin stain was applied for histological analysis and Mallory-Azan staining was applied for histoimmunochemical analysis of antibodies and iNOS (inducible nitric oxide synthase), and desmin was applied to paraffin sections of skin wound specimens. Parameters of oxidative stress were measured in the wound area.ResultsEpidermal thickness and vascularization were increased, and hair root degeneration, edema, cellular infiltration, collagen discoloration, and necrosis were decreased in Sericin group in comparison to the Placebo group and the Sham operated group. Malonyldialdehyde (MDA) levels were decreased, but superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were increased in the sericin group.ConclusionsWe found that sericin had significant positive effects on wound healing and antioxidant activity. Sericin-based formulations can improve healing of incision wounds.
Cypermethrin is a synthetic pyrethroid that belongs to a group of insecticides with low mammalian toxicity but high insecticidal activity. The present study was undertaken to evaluate subacute toxicity of orally administered cypermethrin in rats based on the haematological, enzymological, and histological brain examination. The study was conducted on 8-week old male Wistar rats and Kral 250 EC (250 g of cypermethrin/l) was orally administered (60, 150, and 300 mg/kg) for 28 consecutive day. Thus, the investigation covered four groups of animals: three experimental groups and one control group, of 20 rats each. Our results demonstrated that experimental groups receiving both 150 and 300 mg/kg cypermethrin treatment led to significant dose-dependent decrease in some haematological parameters [red blood cell (RBC) counts, haematocrite (Ht), thrombocyte, and mean corpuscular haemoglobin (MCH) values] at the end of the experiment. When compared with control animals, there were significant increases between initial body weights and final body weights of cypermethrin treated rats, but there was a significant decrease in brain/body weight ratio of the animals of all treated groups. Furthermore, there was no statistical difference between control group and all experimental groups for brain acetylcholinesterase (AChE) and blood cholinesterase (ChE) enzyme activities, although brain AChE activities were increased in rats treated with a dose of 150 and 300 mg/kg cypermethrin. Histologically, some deformation areas due to ischemia and pyknosis of the cytoplasm of the neurons were observed in brain tissues of rats treated with all doses of cypermethrin.
At present, an intensive effort for prevention of neuroma formation following peripheral nerve section continues. It has been recently suggested that surgical pinealectomy (Px) induces elevation of the collagen content in the granulation tissue of a wound, while melatonin application after Px suppresses elevation of the collagen accumulation in the tissue. The aim of the present study was to assess whether melatonin had the ability to suppress collagen production and neuroma formation following peripheral nerve transection. A total of 40 male rats (four groups of 10) were left intact (intact controls) or sham operated (sham group), were Px, or were Px and given melatonin (Px + melatonin group). All animals underwent a surgical intervention consisting of right sciatic nerve neurectomy. After 4 wk, the animals were killed following intracardiac perfusion. Gross morphology of neuroma formation in the proximal nerve segment was examined and proximal neuroma evaluated. Macroscopic and microscopic findings revealed that Px caused a proliferation of connective tissue and large neuroma formation at the proximal ends of transected nerves. Stereological analysis showed that there was a statistically significant reduction in connective tissue content of the same region in Px animals treated with melatonin (P < 0.005). The results achieved in a rodent model of sciatic nerve neuroma formation showed that there was a positive correlation between macroscopic and microscopic observations, and that melatonin enhanced axonal regeneration presumably due to its inhibitory effect on neuroma formation.
BACKGROUND: Cancer is a major public health problem in many areas of the world. Many anticancer drugs in current clinical use have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) is an oxygenated aromatic compound from monoterpene group. It is the main constituent of thyme essential oil and shows antioxidant, antiseptic and antiproliferative properties. The aim of this study is to determine the antiproliferative activity and apoptotic effect of thymol on prostate cancer (PC-3, DU145), breast cancer (MDA-MB-231), and lung cancer (KLN205) cell lines. METHODS: The cancer cells were treated with different concentrations of thymol (100, 200, 400, 600, 800 μM) at 24 h, 48 h and 72 h. The cell viability was investigated by MTT assay and analysis of apoptosis was determined with annexin V assay. RESULTS: The study showed the dose and time-dependent cytotoxic effect of thymol in PC-3, DU145, MDA-MB-231, and KLN205 cancer cell lines. Thymol signifi cantly induced apoptosis in all groups in a dosedependent manner. Statistical analysis showed a signifi cant difference between thymol-treated cell lines compared to the control (p < 0.001). CONCLUSION: The data in the present study demonstrated that thymol has apoptotic and antiproliferative properties in lung, breast and prostate cancer cell lines. Thymol could serve as a potential therapeutic agent in the future (Fig. 5, Ref. 26).
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