Astrocyte response to melatonin treatment in rats under high-carbohydrate high-fat diet.

The involvement of consumption of high-carbohydrate high-fat (HCHF) diet in cognitive impairment is attributed, at least in part, to the activation of astrocytes, which contributes to the development of neuroinflammation, oxidative stress, and subsequent cognitive deficits. This study aimed to assess the influence of melatonin on cognitive impairment and astrogliosis induced by the HCHF diet in rats. Male Wistar rats were fed an HCHF diet for eight weeks to induce obesity and metabolic syndrome. Subsequently, they received oral melatonin treatment for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, alongside the HCHF diet. Cognitive function was evaluated using the Y-maze test, while the levels of proinflammatory cytokines, oxidative stress, and the number glial fibrillary acidic protein (GFAP) positive cells were assessed in the hippocampi and hypothalamus. The consumption of the HCHF diet resulted in weight gain, hyperlipidemia, impaired glucose tolerance, cognitive decline, neuroinflammation, oxidative stress damage, and astrogliosis in rats. Although melatonin treatment did not demonstrate beneficial effects on blood glucose and lipid metabolism, it improved the impaired working memory caused by the HCHF diet. Melatonin exhibited a dose-dependent reduction of astrogliosis, neuroinflammation, and lipid peroxidation while restored superoxide dismutase in the hippocampus and hypothalamus of HCHF diet-treated rats. These findings provide evidence that melatonin inhibits astrocyte activation, thereby attenuating inflammation and minimizing oxidative stress damage induced by the HCHF diet.

Assessment of melatonin's therapeutic effectiveness against hepatic steatosis induced by a high-carbohydrate high-fat diet in rats.

Several studies have demonstrated the protective effects of melatonin against metabolic diseases, such as liver steatosis. However, its therapeutic effects have received less scrutiny. The present study aimed to explore melatonin's therapeutic effectiveness in treating non-alcoholic fatty liver disease (NAFLD) induced by a high-carbohydrate high-fat (HCHF) diet in rats. The NAFLD was developed in male Wistar rats using an HCHF diet for 8 weeks. Afterward, they were given melatonin orally for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, along with the HCHF diet. In addition, six age-matched healthy rats received the highest dose of melatonin (30 mg/kg) for the same duration. Rats on the HCHF diet exhibited obesity, dyslipidemia, hyperglycemia, glucose intolerance, insulin resistance, inflammation, oxidative stress, and liver injury (steatosis). Melatonin treatment at 10 mg/kg and 30 mg/kg reduced body weight, adiposity index, oxidative damage, and inflammation but did not affect impaired glucose metabolism induced by the HCHF diet. Meanwhile, the highest dose of melatonin (30 mg/kg) reduced the liver steatosis index in HCHF rats but caused mild liver damage in healthy rats. In conclusion, using melatonin demonstrated positive outcomes in treating NAFLD induced by the HCHF diet in rats, with no noteworthy effects observed in healthy rats. A moderate dosage of 10 mg/kg of melatonin proved to be a safer and more efficient method for reducing HCHF diet-induced NAFLD in rats. Higher melatonin doses should be cautiously administered due to potential disruptions in lipid metabolism and the risk of liver complications.

Anti-inflammatory Effects of Ziziphus Jujube Mill on LPS-induced Acute Lung Injury in Mice.

Ziziphus Jujuba Mill (Z.J) is a well-known ethnomedical source of biologically active compounds with anti-inflammatory effects. However, its significance in acute lung injury (ALI) has never been studied. The present study aimed to explore whether Z.J could attenuate lipopolysaccharide (LPS)-induced inflammatory responses in an experimental model of ALI. Male BALB/c mice received an intratracheal administration of LPS (n=32) or phosphate buffer saline (PBS) (control, n=8). Within 1, 11, and 23 h post-LPS injection, mice were randomly assigned to receive intraperitoneal treatments of saline, dexamethasone (2 mg/kg), and 100 and 200 mg/kg of Z.J extracts, respectively. 24 h after intratracheal administration of LPS, bronchoalveolar lavage fluid and lung tissues were harvested and assessed for inflammatory cell influx, tumor necrosis factor-α (TNF-α) levels, and histological assessments. Treatment with Z.J extracts (100 and 200 mg/kg) and dexamethasone effectively reduced LPS-induced neutrophil and other inflammatory cell influx into the lung tissue compared to the untreated group. additionally, both doses of Z.J extracts (100 and 200 mg/kg) significantly ameliorated the lung wet-to-dry ratio and histopathological damage. Furthermore, compared to the untreated ALI mice, Z.J extract at the highest dose could significantly reduce the TNF-α level.   The present findings indicated that Z.J could effectively ameliorate LPS-induced ALI inflammatory responses and might be considered a promising alternative therapy for the ALI phenotype.

The maternal reduced uteroplacental perfusion model of preeclampsia induces sexually dimorphic metabolic responses in rat offspring.

BACKGROUND: Offspring born to preeclamptic mothers are prone to obesity, diabetes and hypertension in later life, but still, studies investigating the underlying mechanism are limited. Here, we aimed to investigate the impact of the reduced uteroplacental perfusion (RUPP) rat preeclampsia model on offspring metabolic outcomes. METHODS: Timed pregnant Wistar rats underwent RUPP or sham surgeries on day 14 of gestation. Glucometabolic parameters were evaluated on postnatal days (PND), 14 (childhood), and 60 (young adult). In addition, intraperitoneal glucose tolerance test (IPGTT), homeostatic model assessment of insulin resistance (HOMA-IR), immunohistochemical staining for insulin in pancreatic islets, arterial blood pressure and 24-h urine protein (24hUP) excretion were performed at PND60. RESULTS: Male, but not female, young adult rats (PND60) of RUPP dams exhibited an impaired IPGTT, decreased circulatory insulin and weakened pancreatic insulin immunoreactivity. Compared to the male offspring of the sham group, the body mass of male RUPP offspring significantly caught up after PND42, but it was not sex-specific. RUPP pups also exhibited upregulations in glucagon (only males) and ghrelin (both sexes with a more significant increase in males) during PND14-PND60. However, in sham offspring (both sexes), glucagon levels were downregulated and ghrelin levels unchanged during PND14-PND60. The blood pressure, HOMA-IR and 24hUP values did not alter in RUPP pups. CONCLUSIONS: The overall results suggest that maternal RUPP has negative and sex-specific impacts on insulin, glucagon and ghrelin regulations in offspring and that, as young adults, male RUPP rats may be more prone to develop obesity and diabetes.

Effect of red beetroot juice on oxidative status and islet insulin release in adult male rats.

INTRODUCTION: Beetroot is rich in inorganic nitrate and it has been shown that inorganic nitrate has beneficial effects on metabolic syndrome. This study aims to investigate the effect of red beetroot juice (RBJ) on carbohydrate metabolism in adult insulin-resistant rats. MATERIALS AND METHODS: Sixteen male Wistar rats (32 weeks old) were divided into two equal groups: control and RBJ. Treatment with drinking water (control) and 100% RBJ (RBJ) was lasted for 5 weeks. At the end of the 4th week the intraperitoneal glucose tolerance test was performed and at the end of the study period animals were sacrificed and blood and tissue (aorta, heart, and liver) samples were collected. Furthermore, pancreatic islets were isolated and their insulin secretion activity was investigated in different glycemic conditions. RESULTS: Compared to the control group, RBJ-treated rats showed lower blood glucose and insulin levels in the glucose tolerance test. Serum and tissue levels of nitric oxide in the RBJ group were significantly higher than those in the control group. The liver peroxidation and serum aspartate transaminase levels were significantly increased in the RBJ-treated animals compared to the control group. The islets of RBJ group exhibited lower insulin secretion, especially in 16.7 mM glucose concentration (supraphysiologic condition) than control group. CONCLUSIONS: RBJ consumption improves glucose metabolism in rats via increasing nitric oxide metabolites in an insulin-independent manner. However, future studies are needed to minimize the potential hepatic adverse consequences.

Investigating the effect of the Teucrium polium aqueous extract on the liver of the streptozotocin-induced diabetic rats.

OBJECTIVES: Teucrium polium (TP) has been traditionally used for treatment of the diabetes mellitus, kidney and liver diseases, and inflammations but some studies have reported the hepatotoxicity effects of this plant. Therefore, this study was conducted to investigate the effect of TP aqueous extract on the liver of the diabetic rats. METHODS: Adult male Wistar rats were randomly divided into five groups: (Control) Normal rats that were gavaged with normal saline (1 mL), (TP100) Normal rats (Non-diabetic) that were gavaged with TP (100 mg/kg), (DM) diabetic model rats, which became diabetic by intraperitoneal injection of streptozotocin (50 mg/kg), (DTP100) diabetic rats that were gavaged with TP (100 mg/kg), and (DTP200) diabetic rats that were gavaged with TP (200 mg/kg). The effects of the aqueous extract on the blood glucose, body weight, the activities of enzyme markers of liver damage (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) were investigated in the serum of the control and treated groups. At the end of study liver histopathology and the total antioxidant activity (TAA) test were evaluated. Finally, obtained data were analyzed by the SPSS software (version 16). RESULTS: Results showed that the AST and ALT levels were significantly increased in the diabetic rats (p<0.001). A comparison of 100 mg/kg and 200 mg/kg doses of TP administration in diabetic rats also showed a significant difference (p=0.01), indicating a better performance of 100 mg/kg dose. No significant difference was found between the control group and rats treated by the TP (TP100) (p=0.382). Also, triglyceride (TG) and cholesterol levels were significantly decreased in the treated groups compared to the diabetic untreated group. CONCLUSIONS: Findings of the study revealed no hepatotoxicity, and the hepatoprotective effects of the TP were proved in the present study.

The detrimental effect of cell phone radiation on sperm biological characteristics in normozoospermic.

Radiofrequency electromagnetic radiation emitted from cell phone has harmful effects on some organs of the body, such as the brain, heart, and testes. This study aimed to assess the effects of cell phones on sperm parameters, DNA fragmentation, and apoptosis in normozoospermic. Normal sperm samples were divided into two groups of control and case. The samples from the case were placed for 60 min at a distance of approximately 2.5 cm from the cell phone set in the active antenna position. Control samples were exposed to cell phones without active antennas. All specimens were analysed by World Health Organization criteria. Sperm viability, sperm with chromatin abnormality and maturity, DNA fragmentation, and apoptosis were examined. Viability and motility in the case were significantly lower than the control (p < .001, p = .004 respectively). The percentage of apoptotic sperms and DNA fragmentation were significantly higher in the case when compared with the control (p = .031, p < .001 respectively). The other parameters studied such as morphology, chromatin abnormality, and maturity showed no significant difference between the case and control groups. Cell phone waves had a detrimental effect on human sperm's biological features. Therefore, it is recommended to keep the cell phone away from the pelvis as much as possible.

Ethanolic extract of Achillea wilhelmsii C. Koch improves pulmonary function and inflammation in LPS-induced acute lung injury mice.

OBJECTIVES: Acute lung injury (ALI) is a life-threatening pulmonary dysfunction associated with severe inflammation. There are still no effective pharmacological therapies for the treatment of ALI. In this concern, several anti-inflammatory agents could be used as add-on therapy to inhibit inflammation. Achillea wilhelmsii (AW) C. Koch is a well-known medicinal plant in the Iranian ethnomedical practices with anti-inflammatory activity. This study was aimed to evaluate the efficacy of ethanolic extract of AW on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: The ALI model was established via the intra-tracheal (i.t.) administration of LPS (2 mg/kg) to male BALB/c mice. The ALI mice were divided into four groups (n=8 each) which intra-peritoneally (i.p.) treated with repeated doses of saline (model), dexamethasone (2 mg/kg), and AW (150-300 mg/kg) 1, 11 and 23 h post LPS administration. Twenty-four hours after the LPS challenge, bronchoalveolar lavage fluid (BALF) and lung tissue were evaluated for inflammatory cell influx, level of tumor necrosis factor-α (TNF-α) and histopathological changes. RESULTS: The AW (150-300 mg/kg) treated mice showed lower inflammatory cells infiltration in BALF and TNF-α level when compared to the model group. In addition, LPS induced several pathological alterations such as edema, alveolar hemorrhage and inflammatory cell infiltration into the interstitium and alveolar spaces. Treatment with AW significantly reduced LPS-induced pathological injury. CONCLUSIONS: Taken together, the data here indicated that AW may be considered as a promising add-on therapy for ALI.

Therapeutic potential of Ferula foetida(Bunge) Regel on gastric ulcer model in rats.

The plant Ferula foetida(Bunge) Regel (FFBR) has a long history in Asian traditional medicine. This study aimed to evaluate the ulcer healing potential of FFBR umbel ethanolic extract on acetic acid-induced chronic gastric ulcer in rats. First, the gastric ulcer model was imitated by serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed by ethanolic extract of FFBR umbel (100 mg/kg, 200 mg/kg, and 300 mg/kg), omeprazole (40 mg/kg), or saline for 12 days. Eventually, on the 13th day, animals were sacrificed, and their stomachs were taken out. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. In addition, the expression of NF-κB p65 was investigated by immunohistochemistry. Compared to the untreated rats with gastric ulcer, FFBR extract significantly decreased ulcer area even superior to omeprazole in a dose-dependent manner. Moreover, histological examination revealed that the extract (300 mg/kg) accelerated the epithelialization and differentiation of proliferative cells to mucosal tissue. The FFBR extract (300 mg/kg) increased tissue levels of VEGF and PGE2, but it did not affect MDA levels in rats with gastric ulcers. FFBR treatment (all doses) could significantly inhibit the expression of NF-κB p65 in gastric tissue. Taken together, experimental findings suggested that FFBR could accelerate the healing process of gastric ulcers in rats through mediating NF-κB and VEGF/PGE2 pathways.

The Ameliorative Impact of Centella asiatica on the Working Memory Deficit in Streptozotocin-induced Rat Model of Alzheimer Disease.

Introduction: Alzheimer disease (AD) is a complex neurodegenerative disorder with a progressive nature leading to neural damage and cognitive and memory deficit. The present study investigated the neuroprotective effects of Centella asiatica (CA) in Streptozotocin (STZ)-induced rat model of memory impairment and neuronal damage. Methods: The intracerebroventricular infusion of STZ (3 mg/rat) or saline (as the vehicle) was performed on days 1 and 3. CA (150 and 300 mg/kg/d) was administered through oral gavage for 21 days after model induction. We used the Y-maze test to assess the working memory-related performances of animals. Rats were then sacrificed, and their hippocampi were harvested for evaluation of neuronal density in the cornu ammonis (CA1, CA2, CA3) and Dentate Gyrus (DG) regions using stereology technique. Results: The intracerebroventricular infusion of STZ caused significant working memory impairment demonstrated in the Y-maze apparatus, with a significant decrease in alternative behavior compared to control animals (40.67±2.04 vs 73.00±1.88, P<0.0001). Oral administration of CA (150 and 300 mg/kg each day) for 21 days significantly improved STZ-induced working memory deficit (55.33±3.34 and 57.17±3.81 vs 40.67±2.04, P<0.013, P<0.004, respectively). Furthermore, 21 days of consecutive administration of CA significantly ameliorated STZ-induced neuronal loss in the CA1, CA2, and DG subfields of the hippocampus. Conclusion: Overall, these data demonstrate that CA increases neuronal density and improves cognitive impairment in the STZ-induced rat model of AD, thereby having promising therapeutic potential for neurodegenerative disorders. Accordingly, further studies are needed to determine the exact molecular mechanism of CA protective effects in brain disorders, particularly AD. Highlights: Centella asiatica (CA) improved the STZ-induced working memory deficit.CA could prevent hippocampal neural cell loss dose-dependent manner.CA improved memory through mitigating neuronal loss in hippocampus. Plain Language Summary: Memory loss is the first signs of dementia. It is well known that a healthy diet might be as good for your brain as it is for your heart. Numerous traditionally used medicinal herbs could significantly affect key events culminating in dementia and Alzheimer's disease. Centella asiatica, commonly known as Gotu Kola or Indian Pennywort, is a tropical, medicinal plant native to Southeast Asian countries. It is one of the becoming popular medicinal plants in the world. Centella asiatica (CA) is widely used in different traditional medicine systems for various purposes, such as reducing blood pressure, memory enhancement, and promoting longevity. In the present study, we tested the possible impact of CA leaf and stem extract in an animal model of memory damage. Memory impairment was induced in adult rats by intracerebral infusion of a neurotoxin chemical. Then, the memory-impaired animals were orally treated with 150-300 mg/kg of CA extract for 21 days. Finally, we tested their working memory by placing them in a Y-maze apparatus. Furthermore, their most involved brain part (hippocampus) was dissected, and its cell density was evaluated. Our findings exhibited that CA treatment considerably improved rats' memory performance, indicating by enhancing working memory score in the Y-maze task. In addition, CA treatment significantly prevented neuronal cell loss in the hippocampus of memory-impaired rats. This study shows that CA has beneficial effects on memory and cognitive function.

Investigating the effect of ethanolic extract of Commiphora myrrha (Nees) Engl. gum-resin against hepatorenal injury in diabetic rats.

PURPOSE: Management of hepatorenal complications in diabetic patients is still a challenge for clinicians. The study aimed to investigate the impacts of ethanolic extract of Commiphora myrrha (Nees) Engl.oleo-gum-resin (EEM) against hepatorenal injury in diabetic rats. METHODS: Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in adult male Wistar rats (n = 40); whereas, normal control rats (NC, n = 8) were treated with vehicle solution (citrate buffer, i.p.). Diabetic animals were gavaged with 500 mg/kg of metformin (MET500) and different doses of EEM (100, 300, and 500 mg/kg) once daily for 28 days. Diabetic model (DM) and NC groups were treated with normal saline. Various parameters like fasting blood glucose (FBG), plasma insulin, aspartate transaminase (AST), alanine transaminase (ALT), creatinine (Cr), urea, 24-h urine total protein (UTP), urine volume, and hepatorenal histopathology were assessed at the end of the study. RESULTS: Compared to the NC group, diabetic rats showed marked elevations in FBG, AST, ALT, urea, Cr, UTP, urine volume, and a significant reduction in insulin. Diabetic animals also exhibited severe histopathological alterations in liver and kidney tissues. The EEM treatment could not influence the biochemical and pathological alterations. Treatment with EEM at the dose of 300 mg/kg could slightly ameliorate some pathological alterations (fatty changes and tubular congestion) in hepatic and renal tissues. CONCLUSIONS: These findings demonstrated that EEM treatment at doses up to 500 mg/kg could not effectively slow down the pathological process of hepatorenal damage in diabetic rats.

Evaluation of the in vivo and in vitro safety profile of Cuscuta epithymum ethanolic extract.

OBJECTIVE: Cuscuta epithymum (CE) is one of the most popular medicinal plants in the world. However, detailed information about its toxicity is not available. Hence, this study aimed to evaluate the safety profile of CE ethanolic extract in vitro and in vivo. MATERIALS AND METHODS: The extract's in vitro toxicity profile was investigated on normal fibroblast and cervical cancer cells by cytotoxicity test. In the next step, acute oral and intraperitoneal (i.p.) toxicity of the CE extract was evaluated in Wistar rats and BALB/c mice, respectively. Sub-acute oral toxicity was also examined by administering repeated oral doses of the CE extract (50, 200, and 500 mg/kg) to Wistar rats for 28 days. RESULTS: The CE extract exhibited a significant cytotoxicity on both normal (IC50 0.82 mg/ml, p<0.001) and cancer cells (IC50 1.42 mg/ml, p<0.001). Acute oral administration of a single dose of CE extract (175-5000 mg/kg) did not cause mortality; however, its i.p. administration caused mortality at doses greater than 75 mg/kg (i.p. LD50 154.8 mg/kg). In the sub-acute toxicity test, no significant effects in terms of weight change, organ weights, blood chemistry, or kidney pathology were observed. However, at 200 and 500 mg/kg doses, the CE extract significantly increased liver pathological scores compared to the control group (p<0.05 and p<0.01, respectively). CONCLUSION: CE exhibited toxicities in i.p. acute and repeated oral dose administrations. It showed identical cytotoxicity against normal and cancer cells. This herb must be prescribed cautiously by traditional medicine practitioners.

The protective effect of crocin on cisplatin-induced testicular impairment in rats.

BACKGROUND: Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats. METHODS: Fifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25-100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses. RESULTS: Compared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39, p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL, p < 0.001), germinal layer area (25,886 vs. 35,320 µm2, p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg, p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg, p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area. CONCLUSIONS: These findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats.

In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria.

BACKGROUND: Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. METHODS: In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. RESULTS: Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. CONCLUSIONS: These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

Rosmarinic acid attenuates lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats.

It has been recently demonstrated that rosmarinic acid (RA) through modulation in the amyloidogenic pathway exhibit neuroprotective potential in Alzheimer's disease. However, its effects on non-amyloidogenic pathways such as neuroinflammation (NI) and oxidative stress have not been elucidated carefully. Hence, this study aimed to investigate the effect of RA on cognitive function, cortical and hippocampal oxidant-antioxidant balance, and proinflammatory cytokines production in lipopolysaccharide (LPS)-induced NI in rats. NI was induced by intracerebroventricular injection of LPS (50 µg/20 µL; 10 µL into each ventricle) in Wistar rats. RA (25 and 50 mg/kg.) was intraperitoneally administrated to the experimental groups 30 min before the LPS injection and continued once per day for seven days. Cognitive function was investigated by the Y-maze test, and the production of proinflammatory cytokines and oxidative stress markers were evaluated in their hippocampi (HIP) and prefrontal cortex (PFC). In addition, neuronal damage was evaluated in the HIP subfields histologically. The RA administration could alleviate cognitive impairments caused by NI in LPS-treated rats as evidenced by improved working memory and attenuated neuronal injury in the HIP subfields. RA treatment in a dose-dependent manner prevented the overproduction of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and IL-6 in both the HIP and PFC. RA significantly alleviated the HIP and PFC levels of malondialdehyde (MDA) and nitric oxide (NOx) and enhanced the superoxide dismutase (SOD) activity. These findings demonstrated that RA could also exert its neuroprotective effects by modulating non-amyloidogenic pathways such as inflammation and oxidative stress.

Intra-cerebroventricular Administration of Crocin Attenuates Sleep Deprivation-induced Hyperalgesia in Rats.

INTRODUCTION: Sleep deprivation can cause hyperalgesia and interfere with analgesic treatments. The aim of the present study was to establish an obligatory sleep-abstinence model and also evaluate the effects of Intracerebroventricular (ICV) injection of crocin on pain perception in Wistar rats. METHODS: In this experimental study, 35 adult male Wistar rats were randomly divided into 5 groups (n=7). The intra-ventricular cannulation was done for all rats before sleep deprivation. Sleep deprivation was performed by placing animals on a chamber equipped with an automatic animated conveyor (5 s with an interval of 3 min) for 72 h. Subsequently, the sleep-deprived animals received ICV injection of saline (MOD), Morphine 10 µg (MOR), Crocin 10 ug (Cr10), and Crocin40 µg (Cr40) using a microsyringe. Besides, a non-sleep-deprived group was allocated as a Control Group (NC) and only received an ICV injection of saline. Fifteen minutes after the ICV injections, pain perception was evaluated by the hot plate test (54±0.4°C). RESULTS: Compared with the NC group, latency significantly decreased in the MOD group (6.28±0.48 vs. 4.28± 0.48, P<0.0001). In comparison with the MOD group, both morphine (8.42±1.53) and crocin (7.60±1.45 for Cr10 and 8.14±0.89 for Cr40) could significantly increase latency in the sleep-deprived animals (P<0.0001). There was no statistically significant difference between the Cr10 and Cr40 (P=0.42), Cr10, and MOR (P=0.059) and Cr40 with MOR (P=0.86) groups. CONCLUSION: Our results indicated that crocin could attenuate hyperalgesia induced by sleep deprivation in rats.

Comparison of the Effects of Povidone-Iodine 5%, Polyhexamethylene Biguanide, and Chlorhexidine as a Preoperative Antiseptic in Endophthalmitis Prophylaxis in Patients Undergoing Phacoemulsification Cataract Surgery.

BACKGROUND: This study aims to compare the efficacy and toxicity of povidone-iodine (PI) 5%, polyhexamethylene biguanide (PHMB) 0.02%, and chlorhexidine 0.02% in patients undergoing phacoemulsification cataract surgery. MATERIALS AND METHODS: This single-center, randomized study was done on 330 patients who referred to Feiz hospital in Isfahan and scheduled for cataract surgery. They were assigned randomly to 1 of 3 groups of 110 eyes who received 1 drop of PI 5% in group 1, 1 drop of PHMB 0.02% in group 2 and 1 drop of chlorhexidine 0.02% in group 3. Pre-operative Cultures samples were obtained without any topical application and it was repeated 5 min after use of antiseptic solutions. Cultures were obtained from the inferior conjunctival fornix, using sterile culture swabs while avoiding contact to the eyelids and lashes. RESULTS: The numbers of colony-forming units (CFUs) did not differ significantly among the three groups (P = 0.149 and P = 0.260, respectively). After the intervention, CFUs numbers in the three groups were decreased with a significant difference in both blood and chocolate agars (P = 0.304 and P = 0.136, respectively). Of the 317 eyes, 108 (34.1%) showed no bacterial growth in the pre-preparation period, which was similar in the three groups. Staphylococcus epidermidis was the most common isolated bacteria. Conjunctival injection was significantly different among studied groups (P = 0.0001), five patients in iodine group had severe conjunctival injection and no one in the other group. SPE was significantly fewer in chlorhexidine group than PHMB and iodine groups (P = 0.0001). CONCLUSION: Pretreatment with 5% Povidone-Iodine (PVI) for at least 15 min or repeated applications over 10 min is effective in the reduction of conjunctival organisms, and results in less postoperative endophthalmitis.

Ethanolic extract of Iris songarica rhizome attenuates methotrexate-induced liver and kidney damages in rats.

OBJECTIVE: The long-term sequelae of methotrexate (MTX) remain the major cause of concern for both patients and therapists. Therefore, new approaches to decrease MTX side effects are needed. The study was carried out to evaluate the effects of Iris songarica Schrenk (IS) rhizome extract against MTX-induced hepatic and renal injuries in rats. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided into five groups (n=8) including control, MTX, IS50, IS150 and IS300. Control and MTX groups were only treated orally with saline; whereas, IS50, IS150 and IS300 groups were treated with IS extract at three different doses (50, 150, and 300 mg/kg, respectively). Besides, the MTX and experimental groups were received a single dose of MTX (20 mg/kg) intraperitoneally on day 4. On the ninth day, animals were sacrificed, blood transaminases, urea and creatinine were assessed and the concentration of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) were determined in both liver and kidney tissues. Moreover, hepatic and renal damages were evaluated histopathologically. RESULTS: MTX by increasing oxidative stress (MDA) and decreasing antioxidant capacity (SOD) induced hepatic and renal damages as confirmed by biochemical and histological parameters analyses. However, treatment with IS caused significant improvements in hepatic and renal histological architectures and SOD activity (p<0.01) along with reducing liver enzymes, urea, creatinine and MDA (p<0.01). CONCLUSION: The results of the present study showed that IS extract through antioxidant and probably anti-inflammatory activities, could effectively limit MTX-induced hepatic and renal injuries in rats.

Comparison of postoperative morbidity between conventional cold dissection and bipolar electrocautery tonsillectomy: which technique is better? / Comparação da morbidade pós-operatória entre tonsilectomia por dissecção a friotradicional e por eletrocautério bipolar: qual técnica é a melhor?

Abstract Introduction Tonsillectomy is one of the most common surgeries in the head and neck worldwide. This operation is carried out by different methods, the most frequent of which are the cold dissection and bipolar electrocautery techniques. Objective This study was conducted to assess and compare postoperative morbidity between cold dissection and bipolar electrocautery. Methods This prospective randomized clinical trial was performed on 534 patients who underwent tonsillectomy in Vali-e-Asr Hospital of Birjand, east of Iran from October, 2013 to October, 2015. The patients were systematically selected for cold dissection technique or bipolar electrocautery technique groups. Time of surgery, amount of intraoperative blood loss, postoperative hemorrhage, the intensity of local pain 4 and 24 hours after operation and nausea and/or vomiting were recorded and compared in the two groups to decide which technique is better. The data were analyzed in SPSS software (ver-22). The p-value less than 0.5 was considered significant. Results In this study, 51.7% of the cold dissection technique patients and 50.6% of the bipolar electrocautery technique participants were male. Compared to the cold dissection technique, the average intraoperative blood loss was significantly lower (p < 0.001) in the bipolar electrocautery technique group, while the intensity of local pain 4 and 24 hours after the operation was significantly higher (p < 0.001). Other variables showed no significant differences between the two groups. Conclusion Based on the findings of the present investigation, the bipolar electrocautery technique is suggested for tonsillectomy in children, while the cold dissection technique is preferred for adult patients.

Resumo Introdução A tonsilectomia é uma das cirurgias mais comuns de cabeça e pescoço em todo o mundo. Essa cirurgia é feita por diferentes métodos, os mais frequentes são a dissecção a frio e por eletrocauterização bipolar. Objetivo Este estudo foi feito para avaliar e comparar a morbidade pós-operatória na dissecção a frio e eletrocauterização bipolar. Método Este ensaio clínico prospectivo e randomizado foi feito em 534 pacientes submetidos a tonsilectomia no Vali-e-Asr Hospital de Birjand, no leste do Irã, de outubro de 2013 a outubro de 2015. Os pacientes foram selecionados de forma sistemática para o grupo submetido à técnica de dissecção a frio ou para o grupo com uso da técnica de eletrocauterização bipolar. Para a avaliação acerca da melhor técnica, os seguintes parâmetros foram registrados e comparados entre os dois grupos: tempo de cirurgia, quantidade de perda sanguínea intraoperatória, hemorragia pós-operatória, intensidade da dor local 4 e 24 horas após a cirurgia e ocorrência de náuseas e/ou vômitos. Os dados foram analisados no software SPSS (versão 22). O valor de p inferior a 0,5 foi considerado significante. Resultados Neste estudo, 51,7% dos participantes do grupo técnica de dissecção a frio e 50,6% do grupo técnica de eletrocauterização bipolar eram do sexo masculino. No grupo operado pela técnica de eletrocauterização bipolar a média de perda sanguínea intraoperatória foi significantemente menor (p < 0,001) em comparação à técnica de dissecção a frio, enquanto a intensidade da dor local 4 e 24 horas após a cirurgia foi significativamente maior (p < 0,001). As outras variáveis não apresentaram diferenças significantes entre os dois grupos. Conclusão Com base nos achados da presente investigação, para a tonsilectomia em crianças sugere-se o uso da técnica de eletrocauterização bipolar, enquanto a técnica de dissecção a frio é recomendada para pacientes adultos.

Preliminary In Vivo Safety Evaluation of a Tacrolimus Eye Drop Formulation Using Hydroxypropyl Beta Cyclodextrin After Ocular Administration in NZW Rabbits.

AIM: Tacrolimus is an immunosuppressive drug with higher potency compared to cyclosporine A (as a useful immunosuppressant). We prepared an ophthalmic solution formulation of Tacrolimus using hydroxypropyl beta cyclodextrin (HP-ßCD). In the present study, safety of this formulation was investigated in rabbits. MATERIALS AND METHODS: Formulation containing HP-ßCD, Tacrolimus, Polyvinyl alcohol (PVA) and Benzalkonium Chloride in PBS 7.4 was prepared. Tacrolimus concentration in ophthalmic preparation was 0.05% w/v. Ten male New Zealand white rabbits were housed in clean separated cages. One drop of Tacrolimus prepared formulation and a placebo formulation were applied every 12 hrs in the right and left eyes respectively, for 28 days. RESULTS: This new aqueous formulation of Tacrolimus could improve Tacrolimus solubility about 42 times. Clinical examinations on the 1st, 3rd, 7th, 14th and 28th days of study showed transient redness and conjunctivitis in some cases of both control and intervention groups that was not persistent. At the end of the study, there were no statistical differences between the two groups in corneal epithelial defect, redness or pathological evaluations. CONCLUSION: The results of this study suggest that eye drop formulation of CD-Tacrolimus is safe in preliminary evaluations and can be useful for further studies.