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).

Anti-seizure effect of zinc on PTZ-induced epilepsy in rat model.

Epilepsy is a widespread and mainly severe neurological condition portrayed by recurring spontaneous seizures caused by the brain's abnormal electrical activity. According to new research, inflammation may be both a result and the cause of epileptic seizures. The highest zinc levels in the brain have been found in the hippocampus which is one of the most studied regions of the brain regarding epilepsy. Zinc may have an anti-inflammatory potential as zinc co-factors affect numerous biochemical and physiological reactions. In this study, we evaluated the effects of intraperitoneal zinc administration on seizure activity in murine PTZ model. Rats received either intraperitoneal (IP) zinc sulfate at two different dosages (50-100 mg/kg) or a placebo followed by pentylenetetrazole (IP), a strong seizure-inducing drug. The spike percentages were considerably lower in the PTZ (35 mg/kg) and 50 or 100 mg/kg zinc-treated groups (A3 and A4) than in the PTZ (35 mg/kg) and saline-treated group (A2; p may be used as an adjuvant therapy in combination with other antiepileptic drugs in the future (Tab. 3, Fig. 1, Ref. 27) Keywords: anti-seizure effect of zinc, epilepsy, abnormal electrical activity, antiepileptic drugs, rat model.

The Role of Ankaferd Blood Stopper and Oxytocin as Potential Therapeutic Agents in Endometriosis: A Rat Model.

To evaluate the potential effect of Ankaferd Blood Stopper (ABS) and oxytocin (OT) in an experimental endometriosis model, 18 female Sprague Dawley rats were used in this study. The animals were divided randomly into three groups after surgical induction of endometriosis: group 1: control group (isotonic NaCl, 1 mL/kg/day, intramuscular, n=6); group 2: OT group (OT, 80 U/kg/day, intramuscular, n=6); group 3: ABS group (ABS, 1.5 mL/kg/day, intraperitoneal, n=6). Each group was treated for four weeks (two times per week). Volumes of endometriotic explants were measured in biopsy samples for histopathological analysis. Vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and tumour necrosis factor (TNF-α) levels were measured in plasma and peritoneal fluid. Endometriotic explant volumes were significantly decreased after OT administration (P<0.0001). The epithelial score was significantly decreased in both treatment groups compared to the control group (P<0.05). TUNEL immunohistochemistry showed more apoptotic changes in the endometriosis foci (gland epithelium and surrounding tissue) in the OT group than in the control group (P<0.05). The levels of VEGF, MCP-1, and TNF-α were significantly reduced in the OT group (P<0.05), whereas no significant changes in protein levels were found in the ABS-applied group. The results indicate that OT has greater potential as a therapeutic agent in experimentally induced peritoneal endometriosis, where ABS, which is a VEGF modulator, appears to act through different mechanisms to show its palliative effects on a rat model of peritoneal endometriosis.

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.

The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model.

Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-ß-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-ß, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-ß, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy.

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.

Effect of oxytocin administration on nerve recovery in the rat sciatic nerve damage model.

BACKGROUND: Growth factors such as nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the healing process of nerve injury. Recent researches have also shown that oxytocin administration activates these growth factors of importance for the healing of nerve tissue. The objective of the present study was to evaluate the effects of oxytocin on peripheral nerve regeneration in rats. METHODS: Twenty-four male Sprague-Dawley rats were underwent transection damage model on the right sciatic nerve and defective damage model on the left sciatic nerve. The animals were assigned to one of two groups: control group or treatment group (received 80 mg/kg oxytocin intraperitoneally for 12 weeks). The sciatic nerve was examined, both functionally (on the basis of climbing platform test) and histologically (on the basis of axon count), 3, 6, 9, and 12 weeks after the injury. Also, stereomicroscopic and electrophysiological evaluations were carried out. RESULTS: Significantly greater improvements in electrophysiological recordings and improved functional outcome measures were presented in the treatment group at 12-week follow-up. Stereomicroscopic examinations disclosed prominent increases in vascularization on proximal cut edges in the oxytocin group in comparison with the control group. Higher axon counts were also found in this group. CONCLUSION: Intraperitoneal oxytocin administration resulted in accelerated functional, histological, and electrophysiological recovery after different sciatic injury models in rats.

Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model.

OBJECTIVE: To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment. METHODS: Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 µg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4°C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30°C for hormone assays. RESULTS: All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Müllerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group. CONCLUSION: G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.

High-dose atorvastatin ameliorates the uterine microenvironment in streptozotocin-induced diabetic rats.

Abstract The aim of this study was to investigate whether atorvastatin can ameliorate the uterine microenvironment in diabetes mellitus. Six non-diabetic (control) and 12 diabetic mature female Sprague-Dawley albino rats were used in this study. Diabetes was induced by intraperitoneal injections of 60 mg/kg streptozotocin, and 10 mg/kg/day of oral atorvastatin was administered for 4 weeks via orogastric tubes. The animals were euthanized, and blood samples were collected via cardiac puncture for biochemical analysis. Bilateral hysterectomy was performed for the histopathologic examination. Endometrial gland degeneration and stromal fibrosis scores concomitant with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) immunoexpressions were analyzed. The endometrial gland degeneration scores, stromal fibrosis scores and VEGF immunoexpression was significantly lower, and the EGFR immunoexpression was significantly higher in the atorvastatin-treated diabetic rats when compared to the non-treated diabetic group, suggesting that atorvastatin ameliorates the uterine microenvironment in diabetes mellitus.

Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome.

AIM: The aim of this study was to examine the effects of cholecalciferol on systemic inflammation and memory in the setting of fatty liver disease in rats. MATERIALS AND METHODS: To induce the development of fatty liver disease, the rats were fed a 35% fructose solution over 8 weeks. Group I (n=6) was designated as the control group and fed with standard rat chow. Group II (n=6) was provided with, standard rat chow, and 0.3 µg/kg/day of oral cholecalciferol over a duration of 2 weeks. In addition to standard rat chow, group III (n=6) and group IV (n=6) were given 4 mL of the 35% fructose solution per day via oral gavage for 8 weeks. However, group IV was also given 0.3 µg/kg/day of oral cholecalciferol over 2 weeks. After the treatment period, passive avoidance tasks were performed by all groups. The liver and brain were harvested for subsequent biochemical and histopathologic analyses. KEY FINDINGS: The development of fatty liver extends the memory latency period of passively avoiding tasks after 1 trial. Moreover, there were increases in brain TNF-α and plasma MDA levels according to two-way analysis of variance. Cholecalciferol supplementation decreased the latency period of passively avoiding tasks in rats with hepatosteatosis, and also significantly reduced brain TNF-α and plasma MDA levels. SIGNIFICANCE: Fatty liver may contribute to the development of systemic inflammation, which affects cognition and causes deficits in memory; however, the anti-inflammatory and antioxidant properties of vitamin D may improve the cognitive function of rats with hepatosteatosis.

Effect of oxytocin treatment on explant size, plasma and peritoneal levels of MCP-1, VEGF, TNF-α and histopathological parameters in a rat endometriosis model.

OBJECTIVE: To determine the effects of oxytocin (OT) on surgically induced endometriosis in a rat model. STUDY DESIGN: Twelve female Sprague-Dawley rats were included. After the implantation and establishment of autologous endometrium onto the abdominal wall peritoneum, the rats were randomly divided into two groups, treated with intramuscular oxytocin (OT group, 160µgkg/day, n=6) or isotonic NaCl solution (control group, 1mLkg/day, n=6) for 28 days. To evaluate the therapeutic effects of OT, the explant volumes were calculated and the levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and TNF-α were measured in plasma and peritoneal fluid. Endometriotic explants were examined histologically by semiquantitative analysis. RESULTS: After treatment, the mean endometriotic explant volume was decreased in the OT group (p=0.016). The histopathological score and VEGF immunoexpression of endometriotic explants were significantly lower in the OT group (p=0.007) than in controls (p=0.000). Inflammatory cytokine levels in plasma and peritoneal fluid were considerably decreased in the OT group. Moreover, TUNEL immunohistochemistry clearly demonstrated more apoptotic changes in the mononuclear cells of the OT group compared with controls. CONCLUSION: We suggest that oxytocin might be considered as a potential candidate therapeutic agent for endometriosis.

Comparison of melatonin and oxytocin in the prevention of critical illness polyneuropathy in rats with experimentally induced sepsis.

BACKGROUND: Critical illness polyneuropathy is an acute neuromuscular disorder of critically ill patients and is characterized by limb and respiratory muscle weakness. The purpose of the study was to evaluate the neuroprotective effects of melatonin (MEL) and oxytocin (OT) on the early stage of sepsis by recording compound muscle action potentials and measuring plasma tumor necrosis factor (TNF)-α levels, lipid peroxidation (malondialdehyde; MDA), and total antioxidant capacity. MATERIALS AND METHODS: One hundred adult male Sprague-Dawley rats were included in the study. The cecal ligation and puncture (CLP) procedure was performed to induce the sepsis model. MEL (10, 20, and 40 mg/kg), OT (0.4, 0.8, and 1.6 mg/kg), and a combination of MEL (20 mg/kg) and OT (0.8 mg/kg) were administered intraperitoneally in the first hour of surgery. Electromyography (EMG) studies were achieved 24 h after CLP surgery and then blood samples were collected for biochemical measurements. RESULTS: EMG findings revealed that compound muscle action potential amplitude was significantly decreased and distal latency was prolonged in the CLP group compared with the sham group (P < 0.05 and P < 0.0005). Moreover, the animals that received CLP surgery showed significantly higher TNF-α and MDA levels and lower total antioxidant capacity values than the sham group. The administration of MEL and OT to rats significantly abolished the EMG alterations and suppressed oxidative stress and TNF-α release in CLP-induced rats. CONCLUSIONS: The inflammatory processes and imbalance in oxidative/antioxidative status play important roles in the pathogenesis of critical illness polyneuropathy. We suggest that both oxytocin and melatonin may have beneficial effects against sepsis-induced polyneuropathy in critical illness.