| کلیدواژههای انگلیسی مقاله |
Anesthetics, Local drug-related side effects and adverse reactions, Safety, Liver failure, Rats, Sprague-Dawley, What&,rsquo s Known Amide-based local anesthetics are extensively used for pain management in outpatient surgeries. To date, most studies have mainly focused on the neurological side effects caused by amide-based local anesthetics. What&,rsquo s New This is the first experimental study comparing the safety and side effects of five commonly used amide-based local anesthetics in rats. Articaine and prilocaine with felypressin induced the least effect on hepatic enzymes of rats with abnormal hepatic function. However, in rats with normal hepatic function, lidocaine caused the least hepatic damage. IntroductionAmide-based local anesthetics are extensively used for pain management in outpatient surgeries. 1, In comparison with ester local anesthetics, amide-based local anesthetics are preferred by medical practitioners because of their rapid and stable anesthesia. 2, All types of anesthetics have certain adverse side effects and cause a wide range of symptoms such as neurological signs (mental disorientation), seizures, and cardiac effects (hypotension and cardiac depression). 3,- 5, Following the administration of these anesthetics, their concentration in the bloodstream rises and subsequently, the nervous system is depressed. Since the main metabolism of amide-based local anesthetics is through the hepatic system, 6, a major concern surrounds the safety of these anesthetics in patients with hepatic injury. In individuals with insufficient liver function, the metabolic activity is impaired, resulting in an inability to process these anesthetics. Consequently, the concentration of the drugs in their blood flow remains high leading to possible toxic levels. 7, However, despite the risk of toxicity, amide-based anesthetics remain the most commonly used anesthetics underscoring the importance of safety measures before their administration.To date, most studies have mainly focused on the neurological side effects caused by amide-based local anesthetics. 8,, 9, Although the use of these types of anesthetics is generally considered to be safe, 2, literature on their safety in patients with hepatic injury is scarce. Therefore, the present study aimed to evaluate the hepatic effects of commonly used amide-based local anesthetics in rats with and without induced hepatic failure. To the best of our knowledge, this is the first experimental study that compares five of the most common local anesthetics in order to determine their effect and safety in the setting of hepatic failure.Materials and MethodsThe present randomized experimental study was conducted from September 2015 to September 2016 at the Animal Laboratory Center affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. A total of 96 male Sprague-Dawley rats aged 8 weeks and weighing 140&,plusmn 10 g were obtained from the animal laboratory. Initially, all rats were weighed to inhibit any discrepancies. The rats were housed in standard cages with 12-hour daylight (starting at 8,00 am) at an ambient temperature of 22&,plusmn 2 &,deg C with 55% relative humidity. The rats were given a 5-day acclimatization period with free access to standard chow and water. 10, The usage of and care for rats were in accordance with the Guidelines for Laboratory Animal Care. 11, The study protocol was approved by the Ethics Committee of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1396.48).Based on a simple random sampling method, the rats were divided into three groups. The first group (n=16) served as the control group and was randomly divided into two equal subgroups. Half of the rats received intraperitoneal administration of paracetamol to induce liver failure without local anesthesia. The other half received no medication. The second group (n=40) included rats with induced liver failure that were subjected to local anesthesia. All rats in this group received intraperitoneal administration of paracetamol and were then randomly divided into five equal subgroups. Each subgroup was administered a different type of amide local anesthetic, namely lidocaine, prilocaine with felypressin, lidocaine with epinephrine, mepivacaine, or articaine. The third group (n=40) included rats without liver failure that were subjected to local anesthesia. The rats in this group were divided into five equal subgroups and were administered a local anesthetic agent similar to the second group. All of the drugs were made by EXIR Inc., Tehran, Iran.Liver failure was induced by administration of 1 g/kg body weight paracetamol intraperitoneally using insulin syringes. 12, After four hours, the first blood samples were obtained to evaluate the severity of induced liver damage based on liver enzyme levels, namely aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT). Then, based on the pharmacological toxicity, the rats were administered the maximum recommended doses of the local anesthetic agents through the oral mucosa. 13,- 15, The dosages for each type of amide local anesthetic were, 5 mg/kg lidocaine, 8 mg/kg prilocaine with felypressin, 7 mg/kg lidocaine with epinephrine, 5 mg/kg mepivacaine, 7 mg/kg articaine, and 7 mg/kg prilocaine. Second blood samples were obtained four hours after the first blood samples to compare liver enzyme levels.Statistical AnalysisThe data were analyzed using SPSS software for Windows, version 20.0 (SPSS Inc., Chicago, IL, USA). The Kolmogorov-Smirnov test was used to examine the normal distribution of data. The independent t test and one-way ANOVA test were used to compare the means of normally distributed quantitative data between the different groups. Tukey&,rsquo s HSD post hoc test was used to evaluate differences between the subgroups. Data were presented as mean and standard deviation (SD). P&,lt 0.05 was considered statistically significant. ResultsBaseline and pre-intervention hepatic enzyme levels in the rats of each subgroup are presented in table 1,. There was no significant difference in the initial levels of liver enzymes between different anesthetic agents in both groups (with and without liver failure). After the administration of anesthetics, there was an increase in enzyme levels in all groups. The extent of change in AST, ALT, and GGT levels was significantly higher in rats with induced liver failure compared with those without induced liver failure (P&,lt 0.001). NoneLidocaine (mg)Lidocaine with epinephrine (mg)Prilocaine with felypressin (mg)Mepivacaine (mg)Articaine (mg)P value*,Without liver failureAST41.86&,plusmn 2.7941.87&,plusmn 2.8541.85&,plusmn 2.8542.02&,plusmn 2.5641.78&,plusmn 2.8341.80&,plusmn 2.750.981ALT29.87&,plusmn 3.5629.85&,plusmn 3.6729.86&,plusmn 3.5629.87&,plusmn 3.5029.88&,plusmn 3.5629.87&,plusmn 3.670.990GGT6.50&,plusmn 0.776.54&,plusmn 0.796.56&,plusmn 0.786.55&,plusmn 0.806.52&,plusmn 0.796.50&,plusmn 0.780.251With liver failureAST1957.62&,plusmn 101.921834.87&,plusmn 293.901978.62&,plusmn 298.551869.37&,plusmn 101.152061.61&,plusmn 174.901968.50&,plusmn 150.150.290ALT750.75&,plusmn 94.20786.75&,plusmn 92.73772.50&,plusmn 60.19739.00&,plusmn 64.21775.50&,plusmn 55.66785.85&,plusmn 66.360.736GGT6.62&,plusmn 0.746.37&,plusmn 0.516.87&,plusmn 0.846.12&,plusmn 0.646.37&,plusmn 0.516.62&,plusmn 0.740.211*One-way ANOVA test (Tukey post hoc), AST, Aspartate aminotransferase, ALT, Alanine transaminase, GGT, Gamma-glutamyl transpeptidase, Data are presented as mean&,plusmn SD |
| نویسندگان مقاله |
Rasoul Gheisari |
Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
Peyman Arasteh |
Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Firuzeh Estakhri |
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Hesamoddin Eatemadi |
Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
Aida Jamshidi |
Student Research Committee, Shiraz Dental School, Shiraz University of Medical Sciences, Shiraz, Iran
Mohammad Javad Khoshnoud |
Department of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Maral Mokhtari |
Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
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