Comparison of Protective Effect of Aqueous and Ethanolic Extracts of Propolis against Gastric Ulceration in Rats.

This study focused on the protective effects of different types of propolis extracts on gastric mucosa in indomethacin-induced rats. The animals were divided into nine groups: control, negative control (ulcer), positive control (omeprazole), and experimental groups, which were summarized by 200, 400, and 600 mg/kg, bw for aqueous-based and ethanol, respectively. According to the histopathological evaluation, more than others, the doses of 200 and 400 mg/kg of aqueous-based propolis extracts had different degrees of positive effects on the gastric mucosa. Generally, the biochemical analyses of the gastric tissue showed a correlation with microscopic evaluations. According to the phenolic profile analysis, while pinocembrin (684.34±1.70 µg/ml) and chrysin (540.54±9.06 µg/ml) were the most abundant phenolics in the ethanolic extract, ferulic acid (53.77±0.07 µg/ml) and p-coumaric acid (52.61±0.42 µg/ml) dominated the aqueous-based extract. Also, the total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of the ethanolic extract showed almost nine-fold superiority compared to the aqueous-based extracts. Based on data from preclinical data, it was decided that the best doses for the main goal of the study were 200 mg and 400 mg/kg, bw for aqueous-based propolis extract.

The relationship between experimental 2,4-Dinitrophenol administration and neurological oxidative stress: in terms of dose, time and gender differences.

Although 2,4-DNP is claimed to promote fast weight reduction, it is also related with an intolerable high risk of serious side effects to various tissues. On the other hand, it is known to have neuroprotective effects. These different effects of 2,4-DNP may be due to the administration conditions. For this reason, in this study, it was aimed for the first time to clarify the oxidative changes that occur in the brain during the use of 2,4-DNP, depending on the dose, time and gender. For this purpose, 60 Wistar rats (30 male, 30 female) were divided into ten groups: control groups, short-term/long-term groups and low dose/high dose groups. Except for the control groups, 2,4-DNP was administered to the other groups by oral gavage. End of the experiment, thiobarbituric acid-reactive substances (TBARs), glutathione (GSH), nitric oxide (NOx) and ascorbic acid (AA) levels were measured in the brain tissues of sacrificed animals. 2,4-DNP administration showed attenuation impact on oxidative stress depending on both dose, time and gender. It can be said that it is more beneficial in terms of neuroprotection, especially in the short-term and male groups. In conclusion, our findings suggest that, depending on the dose, time, and gender, 2,4-DNP may be beneficial in the treatment of neurodegenerative disorders.

Investigation Covering the Effect of Boron plus Taurine Application on Protein Carbonyl and Advanced Oxidation Protein Products Levels in Experimental Alzheimer Model.

Alzheimer's disease (AD) is the most common form of dementia that occurs in the brain. This is a chronic neurodegenerative disease which is valid in 60-70% of all dementia patients. Boron, regarded as a potential antioxidant, has the effect of reducing oxidative stress. Taurine, as one of the thiol-containing amino acids, exists at different concentrations in both the neurons and glial cells of the central nervous system. It plays an important role in the protective and adjuvant therapies as an antioxidant due to its characteristics of maintaining the oxidant-antioxidant balance of the body as well as cell integrity and increasing body resistance. Based on this information, our objective was to reveal the effect of boron alone, taurine alone plus co-administration of taurine and boron application on brain tissue protein carbonyls (PC) and serum advanced oxidation protein products (AOPP) levels in the experimental Alzheimer's model. For this purpose, 5 groups were formed in our study which consisted of 30 Wistar albino male rats. The rats were given a single dose of STZ stereotaxically. At the end of this period, the rats were decapitated, plus their brain tissues and blood were removed. Our findings suggested that taurine alone and co-administration of boron and taurine had a decreasing effect on AOPP and PC levels of the experimental Alzheimer model of the rats.

Phenolic, Antioxidant, Antimicrobial, and In-vivo Wound Healing Properties of Potentilla erecta L. Root Extract in Diabetic Rats.

As stated in many ethnobotany studies, Potentilla genus is traditionally used in the treatment of wound healing. In this study, we aimed to investigate to time-course effects of the methanolic extract of Potentilla erecta (P. erecta) (MEPE) on diabetic wounds. The subject of the experiments was 36 Wistar rats, divided into three main groups: non-diabetic control (NDM), diabetic control (STZ-DM), and P. erecta-treated (MEPE). Diabetes was induced by streptozotocin (STZ). Full-thickness excisional skin wounds were opened in rats. The wounds were treated with P. erecta root extract in the MEPE groups. The wound area, wound contraction rate, collagen, thiobarbituric-acid reactive substances (TBARs), nitric oxide (NOx), and glutathione (GSH) levels in wound tissue were determined for the evaluation of the wound healing on days 0, 3 and 7. Phenolic compounds of MEPE were determined by RP-HPLC-UV. The antioxidant properties were spectrophotometrically determined and the antibacterial properties were tested using the microwell-dilution method. Our results demonstrated that MEPE significantly increased wound contraction rate compared to the STZ-DM group on days 3 and 7. MEPE treated rats showed a statistical increase in the levels of NOx, GSH, collagen and a statistical decrease in the levels of TBARs. Our results, for the first time, may indicate that P. erecta root extract improves and accelerates diabetic wound healing and also alters oxidative events.

The effect of a new wound dressing on wound healing: Biochemical and histopathological evaluation.

Electrospinning process has gained importance in the production of wound dressings in recent years. The wound dressings prepared by electrospinning method provide many advantages over conventional wound dressings. The aim of this study was to assess the histological, biochemical, and immunohistochemical evaluation of collagen/doxycycline loaded nanofiber wound dressing in both acute and chronic wound healing. Full-thickness wound model was created on rats and rats were divided in two main groups: normoglycemic (acute) and hyperglycemic (chronic) groups. Each group was divided into three sub groups: not treated (control) group, treated with nanofiber wound dressing group and treated with commercial product group. Wound closure rates were measured. Oxidative events were investigated by biochemical analyses. In addition to histological studies, matrix metalloproteinase, tissue inhibitor of metalloproteinase, vascular endothelial growth factor, basic-fibroblast growth factor, and von Willebrand factor levels were investigated with immunohistochemical studies. According to the biochemical analyses, it was concluded that the nanofiber wound dressing helps to increase antioxidant capacity and decrease lipid peroxidation. Immunohistochemical studies showed that nanofiber wound dressing enhanced angiogenesis and shortened the inflammatory phase. It was concluded that an effective and safe prototype nanofiber wound dressing, which has similar wound healing effect to the commercial product, has been developed to be used in acute or chronic wound treatment.

Protective effects of aqueous extracts of some honeys against HCl/ethanol-induced gastric ulceration in rats.

This study focused on the concept of the possible protective effect of some honey types against HCl/ethanol-induced gastric ulcers in male Wistar albino rats. Rats were pretreated with rhododendron, chestnut, and oak honey orally with doses of 1.25 and 2.5 g/kg, bw (body weight) for three consecutive days. On fourth day, nothing was applied, and after the administration of anesthesia on the fifth day, their stomachs were surgically removed to investigate the histopathological examinations. Besides analyses of some blood serum profiles and antioxidant parameters of gastric tissue, some biochemical properties of honeys were investigated to support the histopathological results. The degrees of ulcer lesions in all groups revealed a statistically significant difference (p = .011). Although this difference originated from the additional ulcerative inducing effect of some honeys, the lower concentration rhododendron honey indicated more promising data than the positive control group (pantoprazole) in consequence of the microscopic and macroscopic evaluations. PRACTICAL APPLICATIONS: As being a member of natural products, honey has acquired fame among the studies in recent years due to its versatility as a source of food and complementary medicine. For contributing to this argument, this comprehensive study was performed and results were focused on the lower concentration of rhododendron honey thanks to its clinical potential with protecting the gastric mucosa. According to the obtained results, our suggestion came into prominence that this honey might be protecting the mucosa, better than the different concentrations of chestnut and oak honeys, by being better-absorbed through the gastric mucosa.

Comparison of Oxidative Effects of Two Different Administration Form of Oxybutynin in the Potential Target Tissues.

Oxybutynin is an important anticholinergic agent that prevents uncontrolled contractions in the treatment of overactive bladder (OAB). However, drugs containing oxybutynin have significant side effects such as dry eyes, dry mouth, increased heart rate, constipation, blurred vision, and confusion. In recent years, new delivery methods for this agent are being searched. One of them is vaginal delivery. In this study, we aimed to compare the effects of oxybutynin on oxidative parameters in the potential target tissues of the oral and vaginal delivery. Female New Zealand white rabbits (n=12) were divided into two groups: oral delivery and vaginal delivery. The animals were sacrificed 48 h after administration and nitric oxide (NOx), thiobarbituric acid-reactive substances (TBARs), and glutathione (GSH) levels were determined spectrophotometrically in the aorta, salivary gland, and small intestine tissue samples. Vaginal delivery significantly decreased NOx levels in all tissue samples as compared to oral delivery (p < 0.05). Moreover, it reduced TBARs levels in salivary gland and aorta tissue samples (p < 0.05). In the light on these findings, it can be said that vaginal delivery may decrease the oxidant-induced side effects of oxybutynin as compared to oral delivery.

Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events.

The reasons that cause delay in wound healing in diabetes are a decrease in the level of growth factors secretion, an increase in the destruction of growth factors and in oxidative stress. Platelet derived growth factor (PDGF) is one of the important growth factors that play a role in all phases of wound healing. This study investigates time-dependent effects of topically PDGF-BB administration on oxidative events on the healing of dorsolateral-excisional wounds in diabetic rats. Forty-two female Wistar-albino rats with streptozotocin-induced diabetes were divided into four groups: control group, untreated group, chitosan-treated group, chitosan + PDGF-BB-treated group. Two identical full-thickness excisional skin wounds were made under anaesthesia in all rats except for the control group. In the PDGF-BB-treated and chitosan-treated groups, the wounds were treated topically PDGF-BB (7 ng/mL, single daily dose) and blank chitosan gel (equal amount) after wounding, respectively. After these administrations, on day 3 and day 7 of wound healing, rats were sacrificed. Thiobarbituric acid reactive substances, glutathione, nitric oxide, ascorbic acid levels, and superoxide dismutase activity in wound tissues were spectrophotometrically measured. PDGF-BB administration significantly increased TBARS levels and non-enzymatic antioxidant levels in early phase of diabetic wound healing. PDGF-BB dramatically reduced NOx levels on day 3 and sharply increased NOx levels on day 7 of wound healing. Consequently, PDGF-BB administration can be effective on oxidative balance in the early phase of diabetic wound healing.

Potential of morin and hesperidin in the prevention of cisplatin-induced nephrotoxicity.

Oxidative stress is one of the important mechanisms of cisplatin-induced nephrotoxicity. Therefore, this study was designed to explore the potential protective effects of morin and/or hesperidin on oxidative stress in cisplatin-induced nephrotoxicity. This study was performed on 42 Wistar rats. Rats were divided into seven groups: control, morin, hesperidin, cisplatin, cisplatin + morin, cisplatin + hesperidin, and cisplatin + morin + hesperidin. Morin and/or hesperidin were given for 10 consecutive days by oral gavage and on the 4th day a single dose of cisplatin (7 mg/kg) was injected intraperitoneally. After administrations, on the 11th day of the experiment the animals were killed, and malondialdehyde (MDA), nitric oxide (NOx), glutathione (GSH) levels and myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD) activity were measured. Cisplatin-treated rats showed increased levels of MDA, and decreased levels of NOx also activity of CAT. Morin and/or hesperidin pretreatment prevent oxidative stress in kidney tissue, while they increase the NOx level, CAT activity, and decrease MPO activity. In conclusion, morin + hesperidin pretreatment may have a significant potential for protection of cisplatin-induced nephrotoxicity.

Investigation of the effect of intracolonic melatonin gel formulation on acetic acid-induced colitis.

The aims of the present study were to develop a colon-specific gel formulation of melatonin with sodium alginate and to evaluate its in vitro characteristics and intracolonic performance on oxidative stress parameters, such as nitric oxide (NOx), malondialdehyde (MDA) and glutathione (GSH) levels in rats with acetic acid-induced colitis. The melatonin-alginate gel formulations were prepared and their physico-pharmaceutical properties were determined. Formulation M5, which contained 3% of sodium alginate and 20% polyethylene glycol, was used for in vivo studies. The in vivo studies were conducted in rats with acetic acid-induced colitis. NOx, MDA and GSH levels were determined and histological investigations were performed. It was found that formulation M5 was the most suitable formulation for the colon-specific melatonin gel, in terms of pH, viscosity, drug release and mucoadhesion properties. The MDA levels in the tissues of Group 2 (treated with an intracolonic gel formulation without melatonin) were found to be significantly higher than in Group 1 (the untreated group). NOx levels decreased with the intracolonic and systemic melatonin treatment in the colitis-induced rats. Neither intracolonic nor intra-peritoneal (IP) melatonin treatment affected GSH levels. The epitelization of the colon tissues in groups administered with intracolonic melatonin, IP melatonin, and the intracolonic gel formulation without melatonin was much better than that found in the untreated group. It was concluded that melatonin participated in various defense mechanisms against the colonic inflammatory process, and that the dose, route and formulation type were the most important parameters in the effectiveness of melatonin.

Effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats.

PURPOSE: The objective of this study was to show the effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats. METHODS: Male rats were divided into control (group 1) and splenectomized (group 2) groups, and after splenectomy, some rats were given Lactobacillus delbruckii subsp. bulgaricus (highest amount of extracellular polysaccharides, 211 mg/l) for 7 days (group 3) or were given the treatment for 7 days before and 7 days after splenectomy (group 4). The plasma and small intestine tissue thiobarbituric acid reactive substances (TBARS), sulfhydryl group, glutathione, ascorbic acid, and nitric oxide metabolites (NO x ) levels were determined by a spectrophotometer. RESULTS: We found increased TBARS levels in both the plasma and small intestine in the splenectomized rats compared to controls. L. delbruckii subsp. bulgaricus supplementation decreased the TBARS levels in the plasma in the splenectomized rats. In this study, the plasma TBARS and NO x levels were decreased by L. delbruckii subsp. bulgaricus supplementation after or both after and before splenectomy (groups 3 and 4). CONCLUSIONS: Together, these data suggest that. L. delbruckii subsp. bulgaricus supplementation is beneficial for decreasing lipid peroxidation and enhancing the antioxidant capacity of systemic and intestinal tissue in splenectomized rats.

A bioactive molecule in a complex wound healing process: platelet-derived growth factor.

Wound healing is considered to be particularly important after surgical procedures, and the most important wounds related to surgical procedures are incisional, excisional, and punch wounds. Research is ongoing to identify methods to heal non-closed wounds or to accelerate wound healing; however, wound healing is a complex process that includes many biological and physiological events, and it is affected by various local and systemic factors, including diabetes mellitus, infection, ischemia, and aging. Different cell types (such as platelets, macrophages, and neutrophils) release growth factors during the healing process, and platelet-derived growth factor is a particularly important mediator in most stages of wound healing. This review explores the relationship between platelet-derived growth factor and wound healing.

Investigation of the effects of local glutathione and chitosan administration on incisional oral mucosal wound healing in rabbits.

The aim of the present study was to investigate the effects of local glutathione (GSH) and chitosan applications on the oxidant events and histological changes that occur, during healing processes in rabbits with incisional intraoral mucosal wounds. For this purpose, discs containing glutathione and chitosan (1:1) were prepared and their physicochemical characteristics were evaluated. New Zealand white rabbits were used in in vivo studies. A standard incision was applied to the oral mucosa of rabbits. The rabbits were divided into four groups, being: an untreated incisional group (n=6), a group treated with discs containing GSH+chitosan (n=6), a group treated with discs containing solely chitosan (n=5) and a group treated with discs containing solely GSH (n=5). The levels of malondialdehyde (MDA), glutathione and nitric oxide (NOx) in the oral wound tissues were measured on the fifth day after the injury. Histological changes in the wound tissues were also investigated. The tissue MDA levels in the group treated with the disc containing GSH+chitosan were found to be lower than those in the other groups. There were no statistically significant differences in terms of tissue GSH and NOx levels between the group treated with the disc comprising GSH+chitosan and the control group that had untreated incision wounds. According to the histological findings, wound healing in the group treated with the disc containing solely chitosan was found to be better than in the other groups. The results of the experiments showed that the local application to the intraoral incision wounds of chitosan+GSH, and chitosan alone, can be effective in the wound healing processes of soft tissues and dental implants.

PDGF supplementation alters oxidative events in wound healing process: a time course study.

Platelet-derived growth factor (PDGF), an important stimulant, plays a role in almost all stages of wound healing process. In various studies, it has been shown that PDGF has healing effects in this process. In the present study, we especially focused on investigating the effects of exogenous PDGF administration on oxidative events during cutaneous wound healing process. Experiments were performed on 42 female Wistar-albino rats. Animals were divided into four groups: control, untreated, chitosan-treated and chitosan + PDGF-treated. Two uniform full-thickness excisional skin wounds were made under anesthesia in all animals except control group. In the chitosan + PDGF-treated groups, the wounds were treated topically with a single daily dose PDGF-BB (7 ng/ml) after wounding. In the chitosan-treated groups, the wounds were treated topically with equal amount of blank chitosan gel. After that, on the 3rd and 7th days of wound healing, the animals were killed. Thiobarbituric acid-reactive substances (TBARS), nitric oxide (NOx), ascorbic acid (AA), glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured spectrophotometrically in the wound tissues. PDGF significantly increased TBARS levels in early phase of wound healing. In contrast, it significantly decreased TBARS levels in later phase of healing. In the chitosan + PDGF-treated group, NOx levels decreased on days 3 and 7 when compared with the chitosan-treated groups. Non-enzymatic antioxidant levels were increased by PDGF administration and this may have contributed to increase in wound tissue antioxidant capacity. In the light of these findings, PDGF supplementation may have altering effects on oxidative events depending on the time in wound healing process.