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This paper has been retracted.
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[This corrects the article DOI: 10.1371/journal.pone.0157431.].
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Co (II) complex (CMLA) was investigated to evaluate the rate of wound healing in rats. Animals were placed into four groups: gum acacia, Intrasite gel, 10 and 20 mg/ml of CMLA. Wounds were made on the dorsal neck area, then treated with Intrasite gel or CMLA; both of these treatments led to faster healing than with gum acacia. Histology of the wounds dressed with CMLA or Intrasite gel displayed a smaller scar width, required less time to heal and showed more collagen staining and fewer inflammatory cells in comparison to wounds dressed with the vehicle. Immunohistochemistry for Hsp70 and TGF-ß showed greater staining intensity in the treated groups compared to the vehicle group. Bax staining was less intense in treated groups compared to the vehicle group, suggesting that CMLA and Intrasite gel provoked apoptosis, responsible for the development of granulation tissue into a scar. CD31 protein analysis showed that the treated groups enhanced angiogenesis and increased vascularization compared to the control group. Furthermore, a significant increase in the levels of GPx and SOD and a decrease in MDA were also observed in the treated groups. This results suggest that CMLA is a potentially promising agent for the wounds treatment.
Subject(s)
Antioxidants , Cobalt , Coordination Complexes , Wound Healing/drug effects , Animals , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Cobalt/chemistry , Cobalt/pharmacology , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Rats , Rats, Sprague-Dawley , Schiff Bases/chemical synthesis , Schiff Bases/chemistry , Schiff Bases/pharmacologyABSTRACT
Manganese is a crucial element for health. In this study, the gastroprotective efficacy of Mn (II) complex (MDLA) against acidified ethanol (HCl/Ethanol)-induced gastric ulceration in rats was evaluated. The animals were distributed into 5 groups. Groups 1 and 2 received carboxymethylcellulose (CMC), group 3 was pretreated with omeprazole, and groups 4 and 5 were given 10 and 20 mg/kg of MDLA, respectively. After one hour, CMC and HCl/Ethanol were given to groups 2-5 whilst the animals in group 1 were ingested with CMC. After sacrifice, gastric lesions were evaluated by wall mucus, gross appearance, histology, antioxidant enzymes and immunohistochemistry. Group 2 displayed severe gastric damage with a significant reduction in wall mucus. Conversely, gastric lesions were reduced in groups 3-5 by 85.72%, 56.51% and 65.93%, respectively. The rats in groups 3-5 showed up-regulation of heat shock protein 70 (Hsp70) with down-regulation of Bcl-2-associated protein x (Bax). Pretreatment with omeprazole or MDLA led to an increase in the uptake of Periodic Acid Schiff (PAS) stain in the glandular part of the gastric tissue, raised levels of prostaglandin E2 (PGE2) and superoxide dismutase (SOD), and a reduction in malondialdehyde (MDA) concentrations. These results suggested the gastroprotective action of Mn (II) complex.
Subject(s)
Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/toxicity , Manganese/administration & dosage , Manganese/toxicity , Stomach Ulcer/drug therapy , Animals , Anti-Ulcer Agents/chemistry , Ethanol/administration & dosage , Female , Gastric Mucosa/drug effects , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Male , Manganese/chemistry , Omeprazole/administration & dosage , Rats, Sprague-Dawley , Schiff Bases , Stomach Ulcer/chemically induced , Toxicity Tests, AcuteABSTRACT
Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson's trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP (P < 0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-ß and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing.
Subject(s)
Antioxidants/metabolism , Chalcones/administration & dosage , Wound Healing/drug effects , Animals , Chalcones/chemical synthesis , Collagen/metabolism , Granulation Tissue/metabolism , Humans , Lipid Peroxidation , Male , Rats , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can result in peptic ulcer disease (PUD) which is a common condition worldwide. The aim of this study was to evaluate the antiulcer properties of (1-(4-hydroxy-phenyl)-3-m-tolyl-propenone) (HPTP) chalcone in rats using indomethacin as ulcerogenic agent. RESULTS: None of the rats showed symptoms of kidney and liver toxicity during the term of the study. Administration of HPTP had decreased the acidity, increased gastric wall mucus and flattening of gastric mucosa and reducing erosive gastric damage area. HPTP also showed dose dependent increase in SOD, GPx activity and PGE2 level and decrease MDA. H & E stain showed decreased infiltration of leucocytes with edema of submucosal layer. PAS staining showed intense uptake of magenta color of gastric wall mucus in rats fed with HPTP, and immunohistochemical staining of gastric mucosa revealed over-expression of HSP70 protein, down-expression of Bax protein and over expression of TGF-ß in rats administered with HPTP. CONCLUSION: This study has revealed that chalcone1-(4-hydroxy-phenyl)-3-m-tolyl-propenone can serve as a safe and effective antiulcer agent as it has been proved to increase pH and gastric wall mucus, increase GPx, SOD, PGE2, and decrease MDA level, ultimately, it has also contributes towards the over-expression of HSP protein andTGF-ß, and down-expression of Bax protein.