In Vivo Biocompatibility of an Ionic Liquid-protected Silver Nanoparticle Solution as Root Canal Irrigant

Introduction: The aim of this study was to assess the biocompatibility of positively charged imidazolium-based ionic liquid-protected nanosilver solution (AgNPs) root canal irrigant. Methods and Materials: Eighteen male 4- to 5-month old Sprague-Dawley rats, weighing 200-300 gr were selected and randomly divided into 5 groups: Normal saline 0.9% (group 1), 5.25% NaOCl (group 2), 2.5% NaOCl (group 3), 2.0% chlorhexidine solution (group 4) and AgNPs at 5.7×10-8 M/L (group 5) were randomly injected in 5 sites of dorsal skin of each rat. Tissue inflammatory reaction were evaluated histopathologically after 2 h, 48 h and 14 days. Statistical analysis was done with SPSS version 21 and the Kruskal-Wallis H and Dunn tests were used to find statistically significant differences. The level of significance was set at 0.05. Result: All solutions irritated the highest tissue response after 48 h. Group 1 showed lower inflammatory response compared to groups 2 and 4 (P<0.05). Group 2 displayed higher inflammatory response in comparison with group 5 (P<0.05). Tissue reaction to group 5 was not more severe than the reaction to group 3 or 4. It also would irritate less inflammatory response compared to group 2 (P<0.05). Conclusion: Comparing with NaOCl and CHX, it is possible to label AgNPs as a tissue compatible agent. Keywords: Biocompatibility; Root Canal Irrigant; Silver Nanoparticl

Pharmacognostic and Anti-Inflammatory Properties of Securigera securidaca Seeds and Seed Oil

Background and objectives: Although weed plants are considered undesirable in a particular situation, some weed seeds can be a valuable and cheap source of therapeutic natural compounds. Securigera securidaca (L.) Degen & Dorfl (Fabaceae) is widely distributed in Europe, Australia and Asia as a weed plant. This study investigated the bioactive compounds of S. securidaca seeds as well as its potential anti-inflammatory properties. Methods:  The fatty acid and sterol content were investigated with gas chromatography–mass spectrometry (GC-MS) and phenolic compounds were detected using high performance thin layer chromatography (HPTLC). The thermostability of the oil was studied using differential scanning calorimetry (DSC). Formalin-induced paw licking test and myeloperoxidase activity were investigated. The study was conducted by creating six groups of rats including a control group (vehicle-treated rats, 250 µL/kg, i.p.), formalin group (50 µL of 2.5% formalin), positive control (paracetamol, 100 mg/kg, i.p), and groups of S. securidaca seed oil (250, 500, 1000, 2000, and 4000 μl/kg, i.p). Results: S. securidaca seeds contained a high level of polyunsaturated fatty acid content including linoleic acid (64.602 ± 0.793%) and oleic acid (15.353 ± 0.461%). Stigmasterol and campesterol were not detected in the oil but it contained esterified β-sitosterol (6.621 ± 0.08 mg/g). The seed oil couldn’t create a significant reduction in the MPO activity. It showed a slight but not significant effect on formalin-induced pain reduction. Conclusion: The seed is a rich source of linoleic acid which makes it a good candidate to be used in the pharmaceutical industry

In Vitro Evaluation of Dynamic Viscosity, Surface Tension and Dentin Wettability of Silver Nanoparticles as an Irrigation Solution

Introduction: The aim of this study was to evaluate dynamic viscosity, surface tension and dentin wettability of a newly introduced imidazolium-based silver nanoparticle solution (Im AgNP) in comparison with three common root canal irrigants. Methods and Materials: The irrigants were Im AgNPs at 5.7×10-8 mol/L-1, 5.25% Sodium hypochlorite (NaOCl), 2% Chlorhexidine (CHX) and 17% Ethylenediaminetetraacetic acid (EDTA) and distilled water (control group). Dynamic viscosity was measured using rotational digital viscometer at 25, 37, 45 and 60°C. Surface tension was evaluated using dynamic contact angle analyzer at room temperature (25°C). Wettability was assessed by contact angle measurement for five groups of 10 dentin samples after each group was treated in each irrigant for 10 min. One-way ANOVA, and post hoc Tukey’s test were used for statistical analysis. Significance was set at P<0.05. Results: Dynamic viscosity of all irrigants decreased as the temperature increased. 17% EDTA was the most viscous solution in all examined temperatures (P<0.05). Viscosity of Im AgNP solution at 25, 37 and 45°C was significantly lower than that of 17% EDTA and 5.25% NaOCl (P<0.05). Im AgNPs exhibited a higher surface tension than other irrigants except distilled water. The wettability of dentin increased when it was in contact with 2% CHX and 5.25% NaOCl while Im AgNPs decreased the wettability of dentin surfaces (P<0.05). Conclusion: Im AgNP irrigant has the potential to reach apical portions of root canals due to its lower viscosity compared to the other tested irrigants. However, it may not bring better penetration inside dentinal tubules because of its higher surface tension. Furthermore, Im AgNPs can influence physiochemical properties of dentin by decreasing its surface wettability.Keywords: Irrigant; Silver Nano Particle; Surface Tension; Viscosity; Wettabilit

Factors affecting drug-induced liver injury: antithyroid drugs as instances

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed

Hepatoprotective effects of Artemia salina L. extract against carbon tetrachloride-induced toxicity

The protective effects of Artemia salina L. extract was examined against carbon tetrachloride (CCl4)-induced cell toxicity. In the in vitro model of study, markers such as cell viability, cellular reduced and oxidized glutathione, and lipid peroxidation in HepG2 cells was evaluated. Human liver cancer cell line HepG2 was treated with CCl4 and Artemia salina extract, and markers of hepatotoxicity were investigated. Artemia salina extract showed significant dose-dependent protective effects against the cytotoxicity of CCl4. This extract was able to normalize the levels of GSH, and thiobarbituric acid-reactive (TBARs), which were altered due to CCl4 intoxication in HepG2 cells. As the oxidative stress markers were ameliorated, it might be concluded that Artemia salina extract possesses protective effects probably due to its antioxidant constituents.</p

Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice

Introduction: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice. Methods: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey’s multiple comparison test. Results: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115). Conclusions: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity

Carnosine Supplementation Mitigates Brain Tissue Markers of Oxidative Stress in a Rat Model of Fulminant Hepatic Failure

Fulminant hepatic failure is a deleterious clinical complication, which leads to hyperammonemia. Ammonia is a noxious neurotoxic agent, which affects brain tissue through different mechanisms. On the other hand, it is well-known that oxidative stress and its consequences play a major role in the pathogenesis of ammonia-induced brain injury. Carnosine is a dipeptide abundantly found in the human central nervous system (CNS). This peptide is widely investigated for its neuroprotective properties. The current study aimed to evaluate the effect of carnosine supplementation on oxidative stress markers in the brain tissue of a rat model of fulminant hepatic failure and hyperammonemia. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. On the other hand, brain tissue markers of oxidative stress including reactive oxygen species (ROS) formation, lipid peroxidation, tissue glutathione content, and total antioxidant capacity were measured. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including ROS formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was evident in the brain of thioacetamide-treated animals. It was found that carnosine supplementation (250, 500, and 1000 mg/kg) decreased serum markers of liver injury, mitigated brain, and plasma ammonia level, and alleviated brain tissue markers of oxidative stress. These data suggest carnosine as a potential neuroprotective agent with therapeutic capability against ammonia-induced CNS injury.</p

Taurine Alleviates Brain Tissue Markers of Oxidative Stress in a Rat Model of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a serious clinical complication, which could lead to coma and death if not appropriately managed. There is agreement on the predominant role of ammonia in the etiology of HE. Brain is one of the most critical organs affected by ammonia. The critical role of oxidative stress and its consequences in the pathogenesis of ammonia-induced brain injury have been revealed before. On the other hand, there is no promising therapeutic option against ammonia neurotoxicity. Taurine is one of the most abundant amino acids in the human body. Several pharmacological roles including brain protecting properties have been attributed to this amino acid. The current study was designed to evaluate the role of taurine supplementation on HE-induced oxidative stress in the brain tissue. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. Moreover, markers of oxidative stress in the brain of hyperammonemic animals were assessed. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was detected in the brain tissue of thioacetamide-treated animals. It was found that taurine treatment (250, 500, and 1000 mg/kg, i.p) alleviated brain tissue markers of oxidative stress and decreased serum biomarkers of liver injury. Furthermore, lower plasma and brain ammonia were detected in taurine-treated animals. These data suggest taurine as a potential protective agent with therapeutic capability against HE-associated central nervous system complications.</p

Wound Healing Activity of a New Formulation from Platelet Lysate

Platelet-rich plasma (PRP) is an attractive preparation in regenerative medicine due to its potential role on the healing process in different experimental models. This study was designed to investigate the wound healing activity of a new formulation of PRP. Different gel-based formulations of PRP were prepared. Open excision wounds were made on the back of male Sprague-Dawley rats, and PRP gel was administered topically once daily until the wounds healed completely (12 days). The results revealed that the tested PRP formulation significantly accelerated the wound healing process by increasing the wound contracting, tissue granulization, vascularization, and collagen regeneration. Interestingly, we found that there were no significant differences between PRP formulation and its gel base in all above mentioned parameters. Although this investigation showed that PRP formulation had significant wound healing effects, but the PRP gel base also had significant wound healing properties. This might indicate the wound healing properties of the PRP gel ingredients in the current investigation.</p

The Hepatoprotection Provided by Taurine and Glycine against Antineoplastic Drugs Induced Liver Injury in an Ex Vivo Model of Normothermic Recirculating Isolated Perfused Rat Liver

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.</p