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Volume 12, Issue 3 (12-2022)                   cmja 2022, 12(3): 260-269 | Back to browse issues page


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Dobakhti F, Yazdinezhad A, Khaleghi H, Naghibi T. Effect of Aqueous Extract of Lettuce on the Outcome of Patients With Traumatic Brain Injury in the Intensive Cares: A Randomized Clinical Trial. cmja 2022; 12 (3) :260-269
URL: http://cmja.arakmu.ac.ir/article-1-892-en.html
1- Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Science, Zanjan, Iran.
2- Department of Pharmacognosy, Faculty of Pharmacy, Zanjan University of Medical Science, Zanjan, Iran.
3- Department of Anesthesiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
4- Department of Anesthesiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. , tnaghibi@zums.ac.ir
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Introduction
Every year, 5.48 million people suffer from Traumatic Brain Injury (TBI). One of the patient’s defense responses to trauma is inflammation. Chronic and severe inflammation can cause harmful complications in the body. Inflammation causes the release of various mediators that play an important role in breaking the blood-brain barrier and resulting in cerebral edema. Various studies have used steroids and non-steroidal anti-inflammatory drugs for the treatment of inflammation caused by TBI. However, due to the side effects of these drugs, such as increased bleeding, platelet disorders, reduced immunity and lack of proper effect, they are not widely used. Therefore, finding a more appropriate method to reduce inflammation caused by TBI seems necessary.
Lettuce (Lactuca sativa) is an edible and annual plant. Various studies have shown the anti-inflammatory effects of lettuce. In a study conducted by Zekkori et al in 2021, the anti-inflammatory, antimicrobial and antibacterial effects of lettuce were reported. Giacomo et al. showed the anti-inflammatory effects of lettuce based on the mechanism of cyclooxygenase reduction. Since brain injuries, especially at young ages, are common in Iran and are one of the main causes of death, the present study aims to investigate the anti-inflammatory effects of lettuce on the outcomes of patients with TBI hospitalized in the Intensive Care Units (ICUs).
Methods
This is a single-center, randomized, double-blind controlled clinical trial (ID: IRCT20151210536). Participants were 32 patients with TBI hospitalized in the Intensive Care Unit (ICU) of a hospital in Zanjan, Iran. Preparation of lettuce extract was done by the hot water percolation method using water at a ratio of 10 in 1 (volume in weight) for 4 hours at 80°C. Of 32 patients, two patients were excluded. The remaining were divided into two groups of intervention (n=15) and control (n=15) by the block randomization method. The intervention group was prescribed lettuce extract on the first day of hospitalization. Then, they received 250 g lettuce extract twice a day for 7 days. The control group was given a placebo. Patients did not know about the type and method of treatment used due to their low consciousness level. The researchers were blind to the group allocation. Acute Physiology and Chronic Health Evaluation (APACHE) form II (a tool for estimating mortality rate) was filled for all patients during admission. C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were checked on the first, third and sixth days. The time and duration of being connected to the ventilator, the time of starting vasopressor use, the number of days requiring vasopressor, the number of days hospitalized in the ICU, the Glasgow Coma Scale (GCS) score at the time of discharge and the mortality of the patients were recorded. Ventilator-associated pneumonia based on the Clinical Pulmonary Infection Score (CPIS) was checked on the third and sixth days. Kolmogorov Smirnov test, independent t-test, repeated measures ANOVA, and chi square test were used to analyze the data.
Results
The amount of total phenol based on standard gallic acid was 68.4 mg/g of plant extract and the amount of total flavonoids based on quercetin was 23.8 mg/g of plant extract. There were 12 men and 3 women in the lettuce group and 9 men and 6 women in the placebo group, and no statistically significant difference was observed between the two groups (P=0.319). The highest age was 81 years in the lettuce group and 84 years in the control group. The lowest age in both groups was 18 years. Mean age (P=0.268), Apache score (P=0.449), and GCS score at the time of admission (P=0.220) had no significant difference between the two groups. There was no difference between the two groups in terms of the duration of being connected to the ventilator (P=0.970), the duration of needing a vasopressor (P=0.288), the number of days hospitalized in the ICU (P=0.418), and GCS score at the time of discharge (P=0.8). The inflammatory markers of IL-6 and CRP were the same between the two groups at the beginning of the study. There was no statistically significant difference between the two groups on the third and sixth days (Table 1). 


In the repeated measures ANOVA, a statistically significant difference was observed in the CRP level among three time points (baseline, day 3, day 6) in both intervention (P=0.037) and control (P=0.019) groups. There was also a statistically significant difference in the IL-6 level among three time points in both intervention (P=0.041) and control (P=0.034) groups. Two people (13.3%) died in the intervention group and 3 people (20%) died in the control group. There was no statistically significant difference in the death rate between the two groups (P=0.95). One patient (6.6%) In the intervention group and 2 patients (3.13%) in the control group had ventilator-associated pneumonia on the third day. On the sixth day, 3 patients (20%) in the intervention group and 5 patients (3.33%) in the control group ha ventilator-associated pneumonia. There was no statistically significant difference between the two groups in ventilator-associated pneumonia on the third (P=0.293) and sixth (P=0.841) days.
Discussion 
Aqueous extract of lettuce has no positive effect on the healing process of patients with TBI which can be due to the small sample size, the short study duration, the illness of the patients, and the influence of confounding factors such as acidosis (which was not investigated in this study) and the difference in the lettuce cultivation method compared to previous studies. There is a need for more clinical trials with a larger sample size.

Ethical Considerations
Compliance with ethical guidelines

The present study was approved by the ethics committee of Zanjan University of Medical Sciences (Code ZUMS.REC.1394.175) and has been registered in the Iran Clinical Trials Registration Center (Code IRCT201512105363). Informed consent was obtained from the patients' families before the start of the study.

Funding
The present study was a part of thesis of third author at Zanjan University of Medical Sciences, which was financially supported by the vice-Chancellor of Research and Technology of the university.

Authors' contributions
Designing and conducting this study: Taraneh Naghibi and Aliraza Yazdinejad; Helping in the data analysis and interpretation of the results: Hamid Khaleghi; conducting the study and prepared the manuscript: Faramarz Dobakhti.

Conflicts of interest
There is no conflict of interest in this research.

Acknowledgements
The researchers are grateful to the personnel working in Ayatollah Mousavi Educational Hospital, as well as all the research units of Zanjan University of Medical Sciences.


References
  1. McDonald SJ, Sharkey JM, Sun M, Kaukas LM, Shultz SR, Turner RJ, et al. Beyond the brain: Peripheral interactions after traumatic brain injury. Journal of Neurotrauma. 2020; 37(5):770-81. [DOI:10.1089/neu.2019.6885] [PMID]
  2. Ng SY, Lee AYW. Traumatic brain injuries: Pathophysiology and potential therapeutic targets. Frontiers in Cellular Neuroscience. 2019; 13:528. [PMID] [PMCID]
  3. Iaccarino C, Carretta A, Nicolosi F, Morselli C. Epidemiology of severe traumatic brain injury. Journal of Neurosurgical Sciences. 2018; 62(5):535-41. [DOI:10.23736/S0390-5616.18.04532-0]
  4. Postolache TT, Wadhawan A, Can A, Lowry CA, Woodbury M, Makkar H, et al. Inflammation in traumatic brain injury. Journal of Alzheimer›s Disease. 2020; 74(1):1-28. [DOI:10.3233/JAD-191150] [PMID] [PMCID]
  5. Wang H, Lynch JR, Song P, Yang HJ, Yates RB, Mace B, et al. Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Experimental Neurology. 2007; 206(1):59-69. [PMID]
  6. Cervellati C, Trentini A, Pecorelli A, Valacchi G. Inflammation in neurological disorders: The thin boundary between brain and periphery. Antioxidants & Redox Signaling. 2020; 33(3):191-210. [DOI:10.1089/ars.2020.8076] [PMID]
  7. Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Experimental Neurology. 2016; 275(Pt 3):367-80. [PMID] [PMCID]
  8. Kalra EK. Nutraceutical-definition and introduction. AAPS PharmSci. 2003; 5(3):27-8. [DOI:10.1208/ps050325] [PMID] [PMCID]
  9. Shi M, Gu J, Wu H, Rauf A, Emran TB, Khan Z, et al. Phytochemicals, nutrition, metabolism, bioavailability, and health benefits in lettuce-A comprehensive review. Antioxidants. 2022; 11(6):1158. [DOI:10.3390/antiox11061158] [PMID] [PMCID]
  10. Sepehri NZ, Parvizi MM, Habibzadeh S, Handjani F. Lettuce as an effective remedy in uremic pruritus: Review of the literature supplemented by an in silico study. Evidence-Based Complementary and Alternative Medicine. 2022; 2022:4231854. [DOI:10.1155/2022/4231854] [PMID] [PMCID]
  11. Zekkori B, Bentayeb A, Ed-Dra A, Filali FR, Sbai A, Chlif N, et al. Effect of hydro-alcohol solvent polarity on the antioxidant, antibacterial and anti-inflammatory activities of four moroccan lettuce varieties (Lactuca sativa L.): A comparative study. Carpathian Journal of Food Science & Technology. 2021; 13(4):133-49. [Link]
  12. Pepe G, Sommella E, Manfra M, De Nisco M, Tenore GC, Scopa A, et al. Evaluation of anti-inflammatory activity and fast UHPLC-DAD-IT-TOF profiling of polyphenolic compounds extracted from green lettuce (Lactuca sativa L.; var. Maravilla de Verano). Food Chemistry. 2015; 167:153-61. [PMID]
  13. Serafini M, Bugianesi R, Salucci M, Azzini E, Raguzzini A, Maiani G. Effect of acute ingestion of fresh and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and antioxidant levels in human subjects. British Journal of Nutrition. 2002; 88(6):615-23. [DOI:10.1079/BJN2002722] [PMID]
  14. Giannoudis PV, Smith MR, Evans RT, Bellamy MC, Guillou PJ. Serum CRP and IL-6 levels after trauma. Not predictive of septic complications in 31 patients. Acta Orthopaedica Scandinavica. 1998; 69(2):184-8. [DOI:10.3109/17453679809117625] [PMID]
  15. Wible EF, Laskowitz DT. Statins in traumatic brain injury. Neurotherapeutics. 2010; 7(1):62-73. [DOI:10.1016/j.nurt.2009.11.003] [PMID] [PMCID]
  16. Lee EJ, Seo YM, Kim YH, Chung C, Sung HJ, Sohn HY, et al. [Anti-inflammatory activities of ethanol extracts of dried lettuce (Lactuca sativa L.)(Chinese)]. Journal of Life Science. 2019; 29(3):325-31. [Link]
  17. Kim MJ, Moon Y, Tou JC, Mou B, Waterland NL. Nutritional value, bioactive compounds and health benefits of lettuce (Lactuca sativa L.). Journal of Food Composition and Analysis. 2016; 49:19-34. [Link]
  18. Sayyah M, Hadidi N, Kamalinejad M. Analgesic and anti-inflammatory activity of Lactuca sativa seed extract in rats. Journal of Ethnopharmacology. 92(2-3):325-9. [PMID]
  19. Altunkaya A, Gökmen V, Skibsted LH. pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants. Food Chemistry. 2016; 190:25-32. [PMID]
  20. Adesso S, Pepe G, Sommella E, Manfra M, Scopa A, Sofo A, et al. Anti-inflammatory and antioxidant activity of polyphenolic extracts from Lactuca sativa (var. Maravilla de Verano) under different farming methods. Journal of the Science of Food and Agriculture. 2016; 96(12):4194-206. [DOI:10.1002/jsfa.7622] [PMID]
  21. Edziri HÁ, Smach MA, Ammar S, Mahjoub MA, Mighri Z, Aouni M, et al. Antioxidant, antibacterial, and antiviral effects of Lactuca sativa extracts. Industrial Crops and Products. 2011; 34(1):1182-5. [DOI:10.1016/j.indcrop.2011.04.003]
  22. Falleh H, Ksouri R, Chaieb K, Karray-Bouraoui N, Trabelsi N, Boulaaba M, et al. Phenolic composition of Cynara cardunculus L. organs, and their biological activities. Comptes Rendus Biologies. 2008; 331(5):372-9. [PMID]
  23. Fancello F, Multineddu C, Santona M, Molinu MG, Zara G, Dettori S, et al. Antimicrobial activities of virgin olive oils in vitro and on lettuce from pathogen-inoculated commercial quick salad bags. Food Control. 2022; 133:108657. [DOI:10.1016/j.foodcont.2021.108657]
  24. Ahmadi N, Fatemi H, Esmaielpour B, soltani- tolarood A. [Effect of bio-priming with plant growth promoting bacteria on growth and biochemical characteristics, phenol, flavonoid, vitamin C and nitrate in lettuce (Lactuca sativa L.) rabicon cultivar in different growth substrates (Persian)]. Journal of Soil and Plant Interactions -Isfahan University of Technology. 2020; 11 (2):41-59. [DOI:10.47176/jspi.11.2.18741]
Type of Study: Research | Subject: Clinical Medicine

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