Zirconium dioxide nanoparticles induced cytotoxicity in rat cerebral cortical neurons and apoptosis in neuron-like N2a and PC12 cell lines.

During recent decades, the application of zirconium dioxide nanoparticles (ZrO2-NP) has been expanded in various fields ranging from medicine to industry. It has been shown that ZrO2-NP has the potential to cross the blood-brain barrier (BBB) and induce neurotoxicity. In the current study, we investigated the in vivo neurotoxicity, as well as, the cellular mechanism of ZrO2-NP toxicity on two neuronal-like cell lines, PC12 and N2a. PC12 and N2a cells were exposed to increasing concentrations of ZrO2-NP (0-2000 µg/ml) for 48 h. The apoptotic effect of ZrO2-NP was determined using annexin V/propidium iodide double staining (by flow cytometry), and western blot analysis of relative apoptotic proteins, including caspase-3, caspase-9, bax, and bcl2. Based on our results, ZrO2-NP at concentrations of 250-2000 µg/mL increased both early and late-stage apoptosis in a concentration-dependent manner. Moreover, the expressions of cleaved-caspase-3 and -9 proteins and the bax/bcl2 ratio were significantly increased. In addition, oral administration of ZrO2-NP (50 mg/kg) to male Wistar rats for 28 days led to the loss of neuronal cells in the cerebral cortex. Taken together, our findings highlighted the role of apoptosis on cytotoxicity induced by ZrO2-NP.

The effect of melatonin on cognitive functions following coronary artery bypass grafting: A triple-blind randomized-controlled trial.

Background: Cognitive dysfunction presents one of the chief causes of postoperative morbidity. Melatonin as a neurohormone can improve neurocognitive functioning and sleep disorders. We evaluated the effect of melatonin on the postoperative cognitive function of patients undergoing coronary artery bypass grafting (CABG). Materials and Methods: A triple-blind randomized-controlled trial was conducted on 66 CABG candidates in Namazee Hospital (Shiraz, Iran). Patients were assigned equally into two groups receiving melatonin 10 mg or a placebo daily for 4 weeks before surgery and 2 days after surgery in the intensive care unit. The Mini-Mental State Examination (MMSE), Tower of London (ToL), and Wechsler Adults Intelligence Scale-Revised (WAIS-R) cognitive function tests were performed in both groups 4 weeks before surgery (time point 1), 2 days after surgery (time point 2), and 6 weeks after initial administration of melatonin (time point 3). Results: The mean change score (time point 3-time point 1) differed significantly between the two groups in the MMSE (P ≤ 0.001), ToL total score (P = 0.001), and WAIS-R general IQ (P ≤ 0.001), picture completion (P ≤ 0.001), vocabulary (P = 0.024), and digit span (P = 0.01). On the other hand, no significant differences were detected in the WAIS-R block design, ToL total time delay, ToL total lab, and ToL total result scores. Conclusion: The MMSE and WAIS-R tests revealed that melatonin might have prophylactic effects against postoperative cognitive disturbance in patients undergoing elective CABG.

Linalool attenuated ischemic injury in PC12 cells through inhibition of caspase-3 and caspase-9 during apoptosis.

Numerous studies have indicated the pharmacological properties of linalool, a volatile terpene alcohol found in many flowers and spice plants, including anti-nociceptive, anti-inflammatory, and neuroprotective activities. The aim of this study was to explore the mechanisms of neuroprotection provided by (±) linalool and its enantiomer, (R)-(-) linalool against oxygen, and glucose deprivation/reoxygenation (OGD/R) in PC12 cells. PC12 cells were treated with (±) linalool and (R)-(-) linalool before exposure to OGD/R condition. Cell viability, reactive oxygen species (ROS) production, malondialdehyde (MDA) level, DNA damage, and the levels of proteins related to apoptosis were evaluated using MTT, comet assay, and western blot analysis, respectively. IC50 values for the PC12 cells incubated with (±) linalool and (R)-(-) linalool were 2700 and 2600 µM after 14 h, as well as 5440 and 3040 µM after 18 h, respectively. Survival of the ischemic cells pre-incubated with (±) linalool and (R)-(-) linalool (100 µM of both) increased compared to the cells subjected to the OGD/R alone (p < .001). ROS and MDA formation were also decreased following incubation with (±) linalool and (R)-(-) linalool compared to the OGD/R group (p < .01). In the same way, pre-treatment with (±) linalool and (R)-(-) linalool significantly reduced OGD/R-induced DNA injury compared to that seen in OGD/R group (p < .001). (±) Linalool and (R)-(-) linalool also restored Bax/Bcl-2 ratio and cleaved caspase-3 and caspase-9 (p < .001, p < .01) following ischemic injury. The neuroprotective effect of linalool against ischemic insult might be mediated by alleviation of oxidative stress and apoptosis.

Adequacy of maternal anesthesia depth with two sodium thiopental doses in elective caesarean section: a randomized clinical trial.

BACKGROUND: Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. METHODS: In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. RESULTS: Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. CONCLUSION: 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. TRIAL REGISTRATION: IRCT No: 2016082819470 N45 , 13/03/2019.

Evaluation of high-dose atorvastatin pretreatment influence in patients preconditioning of post coronary artery bypass graft surgery: A prospective triple blind randomized clinical trial.

Context: Atorvastatin is considered as lipid reductive drugs with anti-inflammatory and pleotherapic effects in coronary artery bypass graph (CABG). Aim: This study is conducted to evaluate the effects of atorvastatin in CABG. Setting and Design: Patients with a coronary bypass graph procedure in Nemazee hospital in Shiraz were divided into two 50-groups receiving high-dose (80 mg) and low-dose (20 mg) atorvastatin. Materials and Methods: Troponin I, creatinine kinase-MB (CK-MB), atrial fibrillation (AF) after CABG, duration of mechanical ventilation, inotrope duration of consumption, blood sugar profile, liver and renal function, death during 30 days of CABG, MACE (major advance cardiac events) during admission in ICU, and 1 month follow up were surveyed. Statistical Analysis: Collected data were analyzed by independent and paired t-test and Chi square. Results: AST was increased, ALT, ALK-P after CABG were decreased, and urine volume in the second day of admission in ICU was increased in the high-dose group. There was an increase and following decrease in blood sugar of patients in the high-dose after CABG. An inflammatory marker after CABG was raised in both groups, ck-mb had an increase, and then followed by a reduction. Troporin had no significant differences between groups. Patients with high-dose atorvastatin had better glomerular filtration rate and renal performance. Along with decreasing AF in the case group, hemodynamics' disorder reduced and there was less bleeding. Conclusion: According to the above, it seems that a short-time prescription of high dose of atorvastatin in CABG can lead to better renal function, decreasing of arrhythmia and AF.

Safranal protects against ischemia-induced PC12 cell injury through inhibiting oxidative stress and apoptosis.

Safranal, isolated from saffron (Crocus sativus L.), is known to possesses neuroprotective effects. In this study, the neuroprotective potential of safranal against PC12 cell injury triggered by ischemia/reperfusion was investigated. PC12 cells were pretreated with safranal at concentration ranges of 10-160 µM for 2 h and then deprived from oxygen-glucose-serum for 6 h, followed by reoxygenation for 24 h (OGD condition). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2,7-dichlorofluorescin diacetate (DCF-DA), and comet assays were used to measure the extent of cellular viability, reactive oxygen substances (ROS), and DNA damage, respectively. Also, propidium iodide (PI) flow cytometry assay and western blotting of bax, bcl-2, and cleaved caspase-3 were performed for assessment of apoptosis. OGD exposure reduced the cell viability and increased intracellular ROS production, oxidative DNA damage, and apoptosis, in comparison with untreated control cells. Pretreatment with safranal (40 and 160 µM) significantly attenuated OGD-induced PC12 cell death, oxidative damage, and apoptosis. Furthermore, safranal markedly reduced the overexpression of bax/bcl-2 ratio and active caspase-3 following OGD (p < 0.05). The present findings indicated that safranal protects against OGD-induced neurotoxicity via modulating of oxidative and apoptotic responses.Graphical abstract The schematic representation of the mode of action of safranal against PC12 cells death induced by oxygen-glucose-serum deprivation and reoxygenation (OGD-R).

Clinical and microbiological features of candiduria in critically ill adult patients in Shiraz, Iran (2016-2018): deviations from international guidelines and fluconazole therapeutic failure.

Candiduria is common among patients admitted to intensive care units (ICUs); however, clinical and microbiological data are limited, which accounts for non-compliance with international guidelines, including over treatment of asymptomatic candiduria that promotes antifungal resistance. This prospective study included adult patients admitted to ICUs of five referral hospitals in Shiraz, Iran, during 2016-2018. Species were identified by MALDI-TOF MS, and antifungal susceptibility was assessed according to CLSI M27-A3/S4. Among 2086 patients, 162 and 293 developed candiduria and bacteriuria, respectively. In total, 174 yeast isolates were collected; 88.5% were Candida albicans (91/174; 52.2%), C. glabrata (38/174; 21.8%), and C. tropicalis (25/174; 14.3%). Antifungal resistance was rare; only two isolates (one C. tropicalis and one C. krusei) were fluconazole resistant. Symptomatic candiduria was noted in 31.4% of patients (51/162); only 37% (19/51) of them were treated and 36.82% (7/19) showed fluconazole therapeutic failure. Two symptomatic patients developed candidemia shortly after candiduria. Among asymptomatic patients, 31.5% (35/111) were overtreated with fluconazole. The mortality rate was 25.3% (41/162); it did not differ between symptomatic and asymptomatic patients. Our results indicate that deviation from standard-of-care treatment for candiduria is a matter of concern given the high rate of fluconazole therapeutic failure among patients with symptomatic candiduria. LAY SUMMARY: Candiduria is an underestimated clinical presentation among critically ill patients and detailed data are scarce in this regard. Given the high rate of fluconazole therapeutic failure and development of candidemia in some cases, the mistreatment of candiduria should not be overlooked by clinicians.

The Effect of Melatonin on the Serum Level of Interleukin 6 and Interleukin 9 in Coronary Artery Bypass Grafting Surgery.

OBJECTIVE: Cardiopulmonary bypass has been recognized as one of the main causes of systemic inflammatory response syndrome, leading to post-operative complications. The aim of this study was to investigate the effect of melatonin on the serum levels of interleukin 6 (IL-6) and IL-9 in patients undergoing coronary artery bypass grafting surgery. METHODS: Forty-four patients undergoing elective coronary artery bypass surgery were randomly allocated into two study groups of melatonin (n = 23) and placebo (n = 21). Patients in the melatonin group received two melatonin tablet, 5 mg daily for 3 days before surgery, 10 mg tablet (two doses of 5 mg) 1 h before induction of anesthesia and finally, 10 mg melatonin tablet in the intensive care unit, placebo group patients received placebo at the same time periods. Serum levels of IL-9 and IL-6 were measured as baseline (T1), before induction of anesthesia (T2), 6 and 24 h after off pump (T3, T4). Data were analyzed using SPSS 23 software (IBM Corp., Armonk, NY, USA). RESULTS: The mean serum level of IL-6 was significantly lower in the melatonin group at T3 and T4 (p ＜ 0.05). Also, in both groups, serum levels of IL-6 in T3 showed a significant increase compared to T1. Serum levels of IL-9 had no significant difference between the two groups at T1, T2, T3, and T4. CONCLUSION: The results of this study showed that pre-operative melatonin administration could modify inflammatory cytokines secretion such as IL-6 while it has no significant effect on the serum levels of IL- 9. Neither of the changes was clinically significant.

Effect of rutin on oxidative DNA damage in PC12 neurons cultured in nutrients deprivation condition.

OBJECTIVES: Rutin is a flavonoid with potent antioxidant property, which exhibited cytoprotective effects in several models of neuronal injury. This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation (SGD) as an in vitro model of neurodegeneration and ischemia. MATERIALS AND METHODS: The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin or α-tocopherol (positive control) and then further incubated for 12 hr in SGD condition. Then, cell viability, DNA fragmentation, lipid peroxidation, generation of reactive oxygen species (ROS), and the expression of proteins involved in apoptosis were determined. RESULTS: The SGD condition significantly decreased viability of the cells, which was accompanied by a significant rise in the generation of ROS and lipid peroxidation. Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation. In addition, rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins (Bax, caspase-3, caspase-9) and increasing the level of anti-apoptotic protein Bcl-2. CONCLUSION: This study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition. Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders.

A comparative, single-blind, randomized study on quetiapine and aripiperazole augmentation in treatment of selective serotonin reuptake inhibitor refractory obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder, of unknown etiology, that affects 2.5% of the population. An appropriate therapeutic response to conventional treatment is seen. Some studies use augmentative treatment by antipsychotics, glutamatergic, lithium, buspirone, and others agents to improve the therapeutic response. In this study, we aimed to evaluate the efficacy and tolerability of aripiprazole and quetiapine as augmentative treatments in patients with selective serotonin reuptake inhibitor (SSRI) refractory OCD. The OCD patients were initially treated for 12 weeks with a SSRI. If after 12 weeks their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score was more than 16, they were randomly assigned to either the aripiprazole or the quetiapine augmentation group for an additional 12 weeks. There were no significant differences in age, sex, education, marital status, or score of Y-BOCS and Clinical Global Impression-Severity Scale (CGI-S) between groups (p > 0.05) at the outset of the study. Significant differences were noted after 1 month when compared with results at 2, 3, and 4 months in both groups (p < 0.001). Both quetiapine and aripiprazole may be effective and well-tolerated augmentative agents in the treatment of SSRI-refractory OCD. Because of positive results, aripiprazole may be considered more effective and may have a more rapid onset in terms of therapeutic response.

A Comparison Between Thiopental Sodium and Propofol for Induction of Anesthesia in Elective Cesarean Section Using Bispectral Index and Isolated Forearm Technique: A Randomized, Double-Blind Study

Objective: Although regional anesthesia is the most frequently used method for selected surgical approaches, general anesthesia (GA) is still common. Awareness and recall of events are among the main hazards during GA, particularly in Caesarean Section (C/S). In this study, we decided to compare depth of anesthesia, that was measured by Bispectral index (BIS) and isolated forearm technique (IFT) in GA, induced by propofol vs. thiopental for elective C/S. We also aimed to determine the incidence of postoperative recall using these two anesthetic medications. Methods: Ninety parturient were allocated to receive either thiopental (group T) or propofol (group P) with blocking on a 1:1 ratio. All patients underwent standard GA. BIS and IFT were used to monitor depth of anesthesia at different predetermined perioperative events. All patients were evaluated for recall of the events. Results: No patient recalled the perioperative events during the follow up period. BIS scores were significantly lower in group P compared with group T after induction of GA until discontinuation of volatile anesthetics (p < 0.001). IFT values were signifi cantly higher in thiopental group in time interval of induction to skin incision comparing to propofol group (p < 0.050). Conclusion: The current study suggests regarding better effect of propofol on decreasing of awareness during anesthesia and surgery, it seems to be better to use propofol in cases where we are forced to use GA in cesarean section.

Evaluation of hyoscine N-butyl bromide efficacy on the prevention of catheter-related bladder discomfort after transurethral resection of prostate: a randomized, double-blind control trial.

BACKGROUND: Transurethral resection of prostate (TURP) is the most common treatment for benign prostatic hyperplasia (BPH). Urinary tract catheter is inserted post-operatively which results in catheter-related bladder discomfort (CRBD) in many patients. The purpose of this study was to assess the preventive effect of hyoscine N-butyl bromide on CRBD caused by a urinary tract catheter after TURP surgery in patients with BPH. METHODS: Twenty-four and twenty-six patients in the treatment and control groups were enrolled, respectively. At the end of the surgery, slow intravenous injection of 20 mg hyoscine N-butyl bromide was administered to the patients of treatment group. The severity of CRBD was followed up at five different time periods and up to 2 h after surgery. RESULTS: On arrival to PACU and after 30 min of injection, statistically significant less CRBD was seen in the treatment group comparing to the control group (P ≤ 0.05 and P ≤ 0.007). The total utilized meperidine dose during PACU stay and the time to discharge for the intervention group were significantly lower than those for the control group (P ≤ 0.0001) with no significant difference in adverse effects (P > 0.05). CONCLUSIONS: Hyoscine N-butyl bromide could reduce the severity of CRBD related to TURP in patients with BPH and their need for analgesic consumption either. It shortened the length of stay in the recovery room. Regarding its availability and low cost, it can be an effective pain relief drug for CRBD discomfort related to TURP in BPH patients.

Berberine protects against glutamate-induced oxidative stress and apoptosis in PC12 and N2a cells.

OBJECTIVES: Neurodegenerative diseases have been associated with glutamatergic dysfunction. Berberine, an isoquinoline alkaloid broadly present in different medicinal herbs, has been reported to have neuroprotective effect. In the present study, the effects of berberine against glutamate-induced oxidative damage and apoptosis were investigated. MATERIALS AND METHODS: The cultured PC12 and N2a cells were pretreated (2 hr) with varying concentrations of berberine (50-1000 µM), followed by exposure to glutamate (10 mM) for 24 hr. The cells viability, intracellular reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) content, superoxide dismutase (SOD) activity, DNA fragmentation and the expressions of pro-apoptotic (cleaved caspase-3 and bax) and anti-apoptotic (bcl-2) proteins were then measured. RESULTS: In both cell lines, pretreatment with berberine (especially at low concentrations) significantly decreased ROS generation, lipid peroxidation, and DNA fragmentation, while improving glutathione content and SOD activity in glutamate-injured cells. Moreover, berberine showed anti-apoptotic effects by reducing the glutamate-evoked caspase-3 and bax/bcl-2 overexpression. CONCLUSION: The results of present study suggest that berberine protects against glutamate-induced PC12 and N2a cells injury by decreasing oxidative stress and subsequently inhibiting apoptosis. This is relevant to berberine treatment in neurodegenerative disorders, such as dementia (Alzheimer's disease), seizures, and stroke.

Evaluation of the Effect of Aminophylline in Reducing the Incidence of Acute Kidney Injury After Cardiac Surgery.

OBJECTIVES: Acute renal failure is a common complication of major cardiovascular surgeries (One-third of patients). Adenosine release as a vascular vasodilator increases after cardiac surgery, which reduces renal and glomerular blood flow and subsequently causes kidney ischemic damage. The present study aimed at evaluating the impact of aminophylline as an adenosine receptor antagonist on renal function after cardiac surgery hoping to find an appropriate method to reduce acute kidney injury. METHODS: The patients in the intervention group received 5 mg/kg aminophylline bolus after induction of anesthesia; then, 0.25 mg/kg/hr of the drug was administered intraoperatively and up to 48 hours after surgery in the ICU cardiac surgery. Similar volume of normal saline was injected to the patients of the second group. Serum BUN, Cr, and GFR were measured pre- and postoperatively and 3 days postsurgery. Patients' 24- hour urine output and RIFLE were also calculated. RESULTS: Those patients who received medication were extubated earlier (P = 0.018) and received lower amount of inotropic drugs (P < 0001). According to the RIFLE criteria, most of the patients experienced no change or even improved GFR and Cr amounts compared to the control group (p < 0.05). GFR and Cr value of all the patients with Cleveland score, less and more than 6, showed a significant difference between the 2 groups (P = 0.001 and P = 0.01, respectively). According to the RIFLE criteria, most of the patients experienced no change or even improved GFR. CONCLUSIONS: Aminophylline in cardiac surgery can reduce the frequency of acute kidney injury according to RIFLE criteria and could be used in the prevention of AKI as a safe and efficient modality in high-risk patients. Also, the use of this drug may reduce the need for inotropic medication at the time of surgery, intensive care unit stay length, and extubation time.

Protective Effect of Diospyros kaki against Glucose-Oxygen-Serum Deprivation-Induced PC12 Cells Injury.

Ischemic cerebrovascular disease is one of the most common causes of death in the world. Recent interests have been focused on natural antioxidants and anti-inflammatory agents as potentially useful neuroprotective agents. Diospyros kaki (persimmon) has been shown to exert anti-inflammatory, antioxidant, and antineoplastic effects. However, its effects on ischemic damage have not been evaluated. Here, we used an in vitro model of cerebral ischemia and studied the effects of hydroalcoholic extract of peel (PeHE) and fruit pulp (PuHE) of persimmon on cell viability and markers of oxidative damage mainly intracellular reactive oxygen species (ROS) induced by glucose-oxygen-serum deprivation (GOSD) in PC12 cells. GOSD for 6 h produced significant cell death which was accompanied by increased levels of ROS. Pretreatment with different concentrations of PeHE and PuHE (0-500 µg/mL) for 2 and 24 h markedly restored these changes only at high concentrations. However, no significant differences were seen in the protection against ischemic insult between different extracts and the time of exposure. The experimental results suggest that persimmon protects the PC12 cells from GOSD-induced injury via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of persimmon for managing cerebral ischemic and other neurodegenerative disorders.

Mechanism of protective effect of lettuce against glucose/serum deprivation-induced neurotoxicity.

OBJECTIVES: The present study investigated the protective effect of ethyl acetate fraction of lettuce (Lactuca sativa) against glucose/serum deprivation (GSD)-induced neurotoxicity, a model which simulates neuronal damage during ischemia. METHODS: Two neuron-like cells, N2a and PC12, were cultivated for 12 hours in GSD condition in the absence or presence of the lettuce fraction. The cell viability, DNA damage, and proapoptotic or antiapoptotic proteins levels were determined using MTT, comet, and immunoblotting assays, respectively. In addition, the intracellular reactive oxygen species and lipid peroxidation levels were measured by fluorimetric methods. RESULTS: In both N2a and PC12 cells, GSD condition significantly decreased the cell viability which was accompanied by increased intracellular reactive oxygen species production, lipid peroxidation level, and oxidative DNA damage. All the GSD-induced neurotoxic changes were inhibited by the lettuce fraction. Lettuce also suppressed the elevated Bax and caspase-3 proteins and decreased Bcl-2 induced by GSD in PC12 cells. DISCUSSION: The present study revealed that lettuce exerts neuroprotective effect through decrease of oxidative stress and inhibition of proapoptotic pathways. Therefore, it has the potential to be used for the management of ischemia-induced neuronal damage.

Water-soluble compounds of lettuce inhibit DNA damage and lipid peroxidation induced by glucose/serum deprivation in N2a cells.

Oxidative stress, increase of lipid peroxidation and resultant DNA damage are associated with pathophysiology of many human diseases such as acute and chronic CNS injuries and diseases, cancer, and also aging. This work was done to investigate whether water fraction from the hydroalcoholic extract of green leaf lettuce (Lactuca sativa L.) can protect N2a cells against glucose/serum deprivation (GSD)-induced lipid peroxidation and DNA fragmentation. The cells were cultivated for 12 h in GSD condition in the absence or presence of the lettuce fraction. The total antioxidant ability of the lettuce water fraction was determined using ferric reducing antioxidant power (FRAP) assay. The intracellular lipid peroxidation was evaluated by malondialdehyde (MDA) level. DNA damage was determined using single cell gel electrophoresis. Using FRAP assay, the antioxidant activity of lettuce water fraction was found to be 574 micromol/g, which is equivalent to 64.1 mg of pure ascorbic acid. Exposure of the cells to GSD condition led to a significant increase of MDA level and DNA fragmentation. Lettuce extract at 400 microg/mL could decrease the elevated intracellular lipid peroxidation and DNA damage. The present study demonstrates that lettuce exerts genoprotective effect through inhibition of oxidative stress.

Genotoxicity and cytotoxicity of mineral trioxide aggregate and calcium enriched mixture cements on L929 mouse fibroblast cells.

Mineral trioxide aggregate (MTA) has shown good biocompatibility in several studies. In the present study, the genotoxic and cytotoxic effects of calcium enriched mixture (CEM) were evaluated compared with MTA using MTT and single-cell gel (comet) assays with serial ascending concentrations (0 to 1,000 µg/mL) of tested materials. Cytotoxicity data indicated that there is no significant difference between CEM and MTA at all concentrations except for the full concentration (1,000 µg/mL); CEM had lower cytotoxicity. Genotoxic effects were more evident with CEM at concentrations of 15.6 and 250 µg/mL; however, was less than that of MTA at concentrations of 500 and 1,000 µg/mL. The cytotoxicity and genotoxicity effects of the two experimental groups generally increased with consistency. Under the conditions of this study, CEM is biocompatible in terms of cyto- and genotoxicity. It appears to be an alternative to MTA as an endodontic biomaterial offering several advantages.