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.

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.

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.

The combined effect of morin and hesperidin on memory ability and oxidative/nitrosative stress in a streptozotocin-induced rat model of Alzheimer's disease.

Alzheimer's disease (AD), the most frequent neurodegenerative disease within dementias, affects the CNS, leading to gradual memory issues and cognitive dysfunction. Oxidative stress in AD contributes to ongoing neuronal loss and hastens disease progression. Notably, the potent antioxidant compounds morin and hesperidin have demonstrated significant effectiveness in addressing oxidative stress. This study explores the impact of morin and hesperidin on behavior and oxidative stress in the streptozotocin (STZ)-induced AD rat model. The experiment involved five groups: control, STZ, STZ+morin, STZ+hesperidin, and STZ+morin+hesperidin. The rat model of AD was created by injecting STZ with the stereotaxic surgery. Morin and hesperidin were applied to the groups for 7-days. After the applications, the Morris water maze (MWM) and novel object recognition (NOR) tests were used and the rats were sacrificed. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), and protein carbonyl (PC) levels were measured. In the STZ group, the levels of NOx and PC exhibited a noteworthy increase compared to the control. Conversely, the application of morin and/or hesperidin treatments reduced NOx and PC levels compared to the STZ group. The co-administration of morin and hesperidin improved the antioxidant status and decreased lipid peroxidation in STZ-induced rats. In the STZ group, serum advanced oxidation protein products (AOPP) levels were statistically elevated compared to the control. However, in the treatment groups, morin and/or hesperidin successfully decreased AOPP levels to those observed in the control. The combined use of these flavonoids may have a neuroprotective effect regarding memory problems and decreasing oxidative/nitrosative stress.

Sinapic acid-loaded gel accelerates diabetic wound healing process by promoting re-epithelialization and attenuating oxidative stress in rats.

Impaired wound healing is a critical health concern for individuals with diabetes. Sinapic acid, a phyto-compound, has wound-healing potential owing to its various bioactivities. In this study, we explored the wound-healing ability of sinapic acid in diabetes. Full-thickness excisional wounds were created in streptozotocin-induced diabetic rats. Sinapic acid-loaded gels (1%, 2%, and 3%) were prepared and applied topically to diabetic skin wounds. On day 7 post-wounding, rats were sacrificed, and macroscopic, histopathological, and oxidative markers of wound healing activity were evaluated in the collected wound tissues. Sinapic acid-loaded gels showed better recovery in re-epithelialization (p < 0.05) and angiogenesis (p < 0.05) compared to the negative control group. Sinapic acid-loaded gels (1%, 2%, and 3%) showed 87.46%, 79.53%, and 68.78% wound contraction, respectively. They increased collagen content (28.05 ± 1.66, 17.30 ± 2.19, and 11.64 ± 1.25, respectively) and decreased malondialdehyde (MDA) levels (17.49 ± 1.61, 18.44 ± 1.24, and 19.16 ± 1.77, respectively) compared to the negative control group (6.76 ± 0.89, and 43.58 ± 3.70, respectively) (p < 0.05). Moreover, sinapic acid-loaded gel groups demonstrated enhanced antioxidant capacity (approximately 2-2.5-fold) compared to the negative control group (p < 0.05). Sinapic acid 1% loaded gel showed the best effect on the diabetic healing process, whereas sinapic acid 2% loaded gel and reference drug showed similar effects. The results of this study, for the first time, suggest that the topical application of sinapic acid can promote diabetic wound healing, especially at low doses.

Cinnamaldehyde and eugenol protect against LPS-stimulated oxidative stress and inflammation in Raw 264.7 cells.

Macrophages are leukocytes that play a strategic role in immune response and can be associated with various diseases due to their effects on the inflammation process and oxidative events. The current study was evaluated the anti-inflammatory and antioxidant properties of cinnamaldehyde and eugenol, which are phyto-compounds with numerous bioactive properties, on lipopolysaccharide (LPS)-induced macrophage cells. For this purpose, Raw 264.7 cells were incubated with cinnamaldehyde or eugenol (15, 25, and 50 µM) then stimulated with LPS. After 24 hr, tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6 levels (as inflammatory mediators), and malondialdehyde (MDA) and nitric oxide (NOx) levels as well as superoxide dismutase (SOD) and catalase (CAT) activities (as oxidative status markers) were determined in cell cultures. Cinnamaldehyde and eugenol pre-treatments decreased TNF-α, IL-1ß, and IL-6 levels as compared to LPS group at all concentrations. Furthermore, these pre-treatments increased SOD activity while decreased MDA and NOx levels as well as CAT activity at different concentrations. Our results demonstrated that these phyto-compounds have potential for the treatment of various diseases as protective agents against chronic inflammation and oxidative stress. PRACTICAL APPLICATIONS: Chronic inflammation and oxidative stress are complications that play a detrimental role in the pathophysiology of many diseases. Alternative treatment methods have been investigated to prevent them. Cinnamaldehyde and eugenol are phyto-compounds with high bioactivity that can be obtained from foods and spices. In this study, the protective effects of cinnamaldehyde and eugenol on lipopolysaccharide-induced oxidative stress and inflammation in macrophage cells were investigated. According to the obtained results, cinnamaldehyde and eugenol pre-treatments decreased inflammation and also reduced oxidative stress. Cinnamaldehyde and eugenol may be a better natural alternative protective agent for the chronic inflammation- and oxidative stress-related diseases.

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.

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.

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.

An ethnobotanical study on medicinal plants in Espiye and its surrounding (Giresun-Turkey).

ETHNOPHARMACOLOGICAL RELEVANCE: This paper provides significant ethnobotanical information on medicinal plants in Espiye in the Black Sea Region. Recording such data calls for urgency. This is the first ethnobotanical study in which statistical calculations about plants are carried out by means of FIC method in Northern (Espiye-Giresun) part of Turkey. This study aims to identify the wild plants collected for medicinal purposes by locals of Espiye which is located in the Black Sea Region of Turkey, and to identify the uses and local names of these wild plants. MATERIALS AND METHODS: A field study had been carried out for a period of approximately 2 years (2012-2014). During this period, information about medicinal use of 55 wild and 15 cultivated plants were collected. Demographic characteristics of participants, names of the local plants, their utilized parts and preparation methods were investigated and recorded. Through face-to-face interviews, we identified and recorded demographic characteristics of the respondents. We interviewed 128 persons who are over the age of 29. The plant taxa were collected within the scope of the study; and herbarium materials were prepared. In addition, the relative significance value of the taxa was determined, and informant consensus factor (FIC) was calculated for the medicinal plants included in the study. RESULTS: We have found out in the literature review of the plants included in our study that 70 plant taxa are already used for medicinal purposes while 3 plants are not available among the records in the literature. The most common families are Asteraceae, Rosaceae, Lamiaceae, Malvaceae, and Ericaceae. We include in our study and report for the first time the medicinal uses of Alchemilla crinita Buser, Stachys sylvatica L., and Thymus leucotrichus Hal. var. leucotrichus Hal. Names of local plants in Turkey vary especially due to vernaculars. The plants that the locals of Espiye use are called with the same or different local names in various parts of Anatolia. CONCLUSION: We found out that locals living in the research area use for therapeutic purpose 70 plants taxa which belong to 36 families. Turkish citizens with different ethnic backgrounds took the questionnaire. These people use these wild plants in treatment of several diseases. Comparison of the data obtained in this study with the experimental data obtained in the previous laboratory studies on the wild plants which grow in Espiye proved ethnobotanical usages to a great extent. Literature review indicated that the therapeutic plants that grow in Espiye are used in different parts of the world for the treatment of similar diseases.

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.