The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

OBJECTIVE: The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. MATERIALS AND METHODS: A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. RESULTS: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. CONCLUSION: It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.

Vitamins C and E protect from sepsis-induced lung damage in rat and CT correlation.

BACKGROUND: Sepsis is one of the leading causes of death in intensive care units worldwide. Vitamins C and E are natural antioxidants and anti-inflammatory agents. Suppressing the inflammation is an important treatment target because it plays a role in the pathophysiology of sepsis. The purpose of this study was to investigate the effect of vitamins C and E treatment in rats with sepsis-induced lung damage. METHODS: In this animal study, fecal intraperitoneal injection procedure (FIP) was performed on 30 of 40 rats included for creating a sepsis model. Rats were randomly assigned into four groups: Group 1, control group (no procedure was applied, n = 10), Group 2, FIP (untreated septic group n = 10), Group 3, FIP+vitC (treated with 500 mg/kg/day ascorbic acid, n = 10), and Group 4, FIP+vitE (treated with 300 mg/kg/day alpha-tocopherol, n = 10). Chest CT was performed in all rats and density of the lungs was measured by using Hounsfield unit (HU). Histopathological examination of lung damage was performed, and blood samples were collected for biochemical analysis. RESULTS: TNF-α, CRP, IL 1-ß, IL-6, and MDA plasma levels in groups treated with vitamin C or vitamin E were lower than in the FIP group. Histological scores in groups treated either with vitamin C or vitamin E were significantly lower as compared to those in the FIP group. The HU value of lung in groups treated wither with vitamin C or vitamin E were lower than that in the FIP group (p < 0.05). CONCLUSION: The rats treated either with vitamin C or E showed improved results for sepsis. We think that they can be used as adjuvant therapy for septic patients because of their effectivity and low costs (Tab. 3, Fig. 2, Ref. 27).

Preparation of Ethanol Extract of Propolis Loaded Niosome Formulation and Evaluation of Effects on Different Cancer Cell Lines.

Propolis is a candidate for cancer treatment with its activity against different tumor cells and, has a wide spectrum of biological and pharmacological activities due to the diversity of its components. In this study, antitumorigenic activities of ethanol extract of propolis (EEP) and ethanol extract of propolis loaded niosome (PLN) were compared using 2D and 3D cell culture. Niosome formulations were prepared by thin film hydration technique. Cell viability of EEP and PLN was analyzed on MCF7, A549, MDA-MB-231, SK-MEL, SK-BR-3, DU145 and L-929 cell lines using MTT assay. L929, MCF7 and A549 cells were cultured using the 3D petri dish technique and their spherical forms were obtained after 142 h. After 24 h, PLN and EEP application, cell viability analysis was performed on 3D cultures with WST assay. As a result, niosome formulations containing EEP showed higher activity than ethanol extract of propolis in cancer cells. While a slow decrease was observed in cell viability in EEP treated cancer cells, it was observed that the percentage viability rates decreased in a shorter time in PLN treated cancer cells. Also, PLN can be used as an anticancer activity drug such as Doxorubicin, but this is not the case for EEP.

The Effect of Botulinum Toxin on Flap Viability of the Posterior Thigh Perforator Flap in Rats.

BACKGROUND: The use of perforator propeller flaps in lower limb reconstruction has increased recently. Many pharmacological agents are used to increase flap viability. Botulinum toxin has been used in various types of flaps in the literature. However, there is no study regarding the use of botulinum toxin in the lower limb propeller flaps. This study investigates the effect of botulinum toxin administration on flap survival for lower limb propeller flap in rats. MATERIALS AND METHODS: The study included 20 male Wistar albino rats, divided into two groups with a flap rotation of 90° in group 1 and 180° in group 2. In both groups, botulinum toxin was administered to the right thigh and a physiological saline solution was applied to the left thigh. Five days later, flaps were elevated over the posterior aspect of the right and left thighs and inset after 90° and 180° rotation was performed. Histopathological, immunohistochemical, and necrosis area analyses were performed. RESULTS: Necrosis area, edema, polymorphonuclear leukocyte infiltration, and necrosis were found to be higher on the left side of the groups, whereas epidermal thickness, collagen density, vascularization, and hair root density were found to be higher on the right side of the groups. No significant difference was found between the right posterior thighs in either group on any parameter other than vascularization. Histopathologically and immunochemically statistically significant differences were found between the two groups. CONCLUSIONS: The present study found that botulinum toxin increases flap viability in lower limb perforator-based propeller flaps.

Comparison of the Effects of Electroacupuncture and Melatonin on Nerve Regeneration in Experimentally Nerve-Damaged Rats.

Background: Development of methods to accelerate nerve regeneration in peripheral nerve damage is important. Electroacupuncture is a new therapeutic method that combines traditional acupuncture with modern electrotherapy. Melatonin has been shown to reduce nerve damage. Objectives: In this study, we aimed to determine and compare the therapeutic effects of electroacupuncture and melatonin on rat sciatic nerve injury. Methods: A total of 56 adult male Wistar Albino rats were divided into four study groups with 14 animals in each group: intact control (group I), subcutaneous saline (group II), subcutaneous melatonin (group III), and electroacupuncture (group IV). Surgical procedure including unilateral (right) sciatic nerve injury was applied to groups II, III, and IV. Saline and melatonin started immediately after surgery for six weeks, while electroacupuncture was given two weeks after surgery for 3 weeks. Functional and histological assessments were used as outcome measurements. Results: Sciatic nerve damage caused a significant decrease in nerve conduction velocity. Both electroacupuncture treatment and melatonin treatment significantly increased the nerve conduction velocity. Both sciatic functional recovery and histological regeneration were faster in these treatment groups compared to the saline. However, no significant difference was observed between the two treatment groups. Conclusion: Electroacupuncture and melatonin are promising alternative treatment strategies for peripheral nerve damage and can be examined in detail in future studies.

The healing effects of Hyperium perforatum (St. John's Wort) on experimental alkaline corrosive eosephageal and stomach burns.

BACKGROUND: The most frequent etiologic cause is alkaline substances. We investigated the protective effects of the plant St. John 's Wort (Hypericum perforatum). METHODS: We included 42 Wistar albino rats weighing between 200-300 grams and divided into six groups as Group 1: Control, Group 2: Burn+Saline (BS), Group 3: Burn+St. John's Wort (BSJW), Group 4: Burn+Plasebo (BP), Group 5: St. John's Wort (SJW), Group 6: Placebo (P). After 15 days of treatment, esophagus, stomach and liver tissue samples were derived by dissection for histopathologic and biochemical markers. The cytotoxic effects of formulation on fibroblasts is evaluated in vitro on human dermoblast fibroblast line (HDFa, Gibco Invitrogen cell culture, C-013-5C). RESULTS: The weight of the rats increased in Group 1, 3, 4, 6, decreased in Group 2 and did not change in Group 5. In the BSJW group, submucosal collagen accumulation, muscularis mucosa damage, tunica muscularis damage and collagen accumulation in esophagus were similar to the control group but lesser than BS and placebo group. In the stomach, mucosal damage, gastric gland dilatation, submucosal polymorphonuclear infiltration were similar to the control group and lesser than the BS group. The lethal concentration of SJW was 2.58 gr/mL. CONCLUSION: SJW substrate is effective in protecting the esophagus and stomach in mild to moderate alcali corrosive burns in the subacute period. We should keep in mind the protective effects of STW substrate in alkaline corrosive burns of the gastrointestinal system.

Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats.

The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A), which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni), on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ). Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions.

Positive effects of ceftriaxone on pentylenetetrazol-induced convulsion model in rats.

AIMS: Many drugs have been associated with seizures as a side effect. Although they are defined as safe for nervous system. The effect on proconvulsant activity of beta lactam antibiotics have been also reported. We aimed to investigate whether ceftriaxone has an anticonvulsant effect on PTZ-induced seizures in rats. MATERIALS AND METHODS: 36 male Sprague-Dawley rats, 18 of them for EEG recording and 18 of them are for behavioral studies, were randomly divided in two groups: group A for EEG recordings and group B for behavioral assesment. About 70 mg/kg PTZ was used for behavioral studies after Ceftriaxone administiration. About 35 mg/kg PTZ were used for EEG recording after ceftriaxone administiration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale, first myoclonic jerk onset time, spike percentages, brain MDA and SOD levels were evaluated between the groups. RESULTS: First myoclonic jerk onset time was significantly shorter in saline group than both 200 and 400 mg/kg ceftriaxone groups (p < 0.05). Racine's convulsion scale was significantly lower in 200 and 400 mg/kg ceftriaxone groups than saline group (p < 0.01, p < 0.0001). Both of two ceftriaxone groups have lower spike percentages than the saline group (p < 0.05). Significantly lower MDA levels and higher SOD activity were determined in 200 mg/kg ceftriaxone group compared with the saline group (p < 0.05). CONCLUSION: Our study demonstrated that ceftriaxone has protective effects on PTZ-induced convulsions and on oxidative damage associated with PTZ.

Investigation of acute effects of Hypericum perforatum (St. John's Wort-Kantaron) treatment in experimental thermal burns and comparison with silver sulfadiazine treatment.

BACKGROUND: Hypericum perforatum (HP) (St. John's Wort-Kantaron) has been used widely for the treatment of burn injuries for many years in traditional Turkish medicine. The aim of study was to investigate HP treatment in experimental thermal burns and compare it with silver sulfadiazine (SS) treatment. METHODS: Thirty-five rats were randomly assigned to one of the five groups, 7 rats in each. A second-degree thermal burn was created on the dorsal sites of rats by exposing an area of 4×4 cm to 100 °C boiled water for 10 seconds. All groups were provided with irrigation for three (3) minutes with 50 cc saline solution (SS). Group 1 (Control Group) was not administered any treatment. Group 2 (Burn Control Group) was administered only irrigation, Group 3 (topical silver sulfadiazine [SS]) was administered SS twice a day, Group 4 (the Topical HP Group) was administered HP four times a day (every six hours), Group 5 (treatment with agent -gel-) was administered other topical material used for the preparation of HP four times a day (every six hours). Wound site healing on the skin was histopathologically evaluated. RESULTS: It was found that collagen discoloration of the HP treatment group was localized in the lower part of the epidermal layer and did not go up to the depth of dermis compared to the other groups, and epidermis, hair follicles and sebaceous glands remained protected compared to the groups administered burn, gel and SS in every hour of the experiment and it was the group closest to the control group structurally. It was determined that the epidermal thickness and the number of vessels of the HP Group were significantly higher compared to the other groups (p<0.05), which was the group closest to the control group in terms of these parameters and these numbers did not show any difference within hours (p>0.05). The number of degenerated hair follicles in the HP Group was significantly less than the other groups (p <0.05), and it was determined that the total number of hair follicles significantly increased in the twenty-fourth (p<0.05) and this number did not differ by the control group (p>0.05). CONCLUSION: Administration of HP four times a day within the first 24 hours is clearly effective in wound healing in the experimental thermal second degree burn modality and is significantly superior to SS treatment.

The effect of melatonin on a dorsal skin flap model.

BACKGROUND: Melatonin (Mel) has a very potent antioxidant activity, depending mainly on its capacity to act as an electron donor. Recently, the antioxidant property of Mel has been much emphasized. In this study, the dorsal skin flap model was used to investigate the effect of Mel in flap viability in rats. MATERIAL AND METHODS: Totally 28 Wistar Albino rats were divided into four groups: control group (C) (n = 7), local treatment group (L) (n = 7), systemic low-dose melatonin treatment group (LT) (n = 7), and systemic high-dose melatonin treatment group (HT) (n = 7). The necrosis rate of the skin flaps was observed seven days after the operation by a blinded observer. Oxidative stress was assessed by determining malondialdehyde (MDA) level, and effects of melatonin on antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were measured. Vascularity, epithelial thickness, and fibroblast proliferation of dorsal skin flaps were assessed histologically. RESULTS: Amount of MDA were found significantly lower (p < .05), and the flap viability, CAT, SOD, vascularity, fibroblast proliferation, and epithelial thickness were found significantly higher (p < .05) in groups HT than in groups C, L, and LT statistically. CONCLUSION: Our results showed that the usage on different doses of melatonin could play an important role in the process of flap viability and further studies will focus on these areas of interest.