Effect of Giving Snakehead Fish Extract ( Channa striata ) on Albumin, Neutrophil, and Lymphocyte Levels in Hypoalbuminemia Patients

: Hypoalbuminemia is a condition where the albumin level in the blood falls below normal. Hypoalbuminemia is known as a marker of protein energy malnutrition, inflammation, infection, liver disease, kidney disease and postoperative stress. In Indonesia, malnutrition hospital data shows 40-50% of patients have hypoalbuminemia or are at risk of hypoalbuminemia, 12% of them are severe hypoalbuminemia, and the hospitalization period for patients with hospital malnutrition shows 90% longer than patients with good nutrition. Decreased albumin levels can be associated with a decrease in the immune system and slow healing of tissues/wounds due to infection. Neutrophils and lymphocytes whose numbers increase when inflammation occurs. Oral administration of high protein with snakehead fish extract ( Channa striata ) is an alternative treatment for hypoalbuminemia. Objective: The purpose of this study was to determine the effect of snakehead fish extract (Channa striata) on albumin, neutrophil, and lymphocyte levels in hypoalbuminemic patients. Method: Articles are compiled using a systematic method literature review , involving national and international journals by taking journals through Google scholar, Pubmed, Research Gate, Scient direct. Results: There was an effect of giving snakehead fish extract on albumin levels, neutrophil values, and lymphocyte values in hypoalbuinemic patients and experimental animals. Conclusion: The content of amino acids, albumin, Zn, Fe, Cu and unsaturated fatty acids in snakehead fish ( Ophiocephalus striatus) is quite effective as an effort to increase albumin levels, decrease neutrophil and lymphocyte values when inflammation occurs in hypoalbuminemic patients.


INTRODUCTION
Hypoalbuminemia is a condition in which the albumin level in the blood falls below normal.Hypoalbuminemia is known as a marker of protein energy malnutrition, inflammation, infection, liver disease, kidney disease and postoperative stress (Levitt , D , 2016).Akirov's research, A (2017) showed that hypoalbuminemia was found in 19.8% of patients with nervous system disorders, 14.1% of patients with respiratory disorders, 12.9% of patients with circulatory system disorders, 10.2% of patients with gastrointestinal disorders, and about 10 ,2% of patients with disorders of the hepatobiliary system.Epidemiological data on hypoalbuminemia in Indonesia are generally still limited.In Indonesia, malnutrition hospital data shows that 40-50% of patients have hypoalbuminemia or are at risk of hypoalbuminemia, 12% of them are severe hypoalbuminemia, and the hospitalization period for patients with hospital malnutrition shows 90% longer than patients with good nutrition.Research by Kurniawan W, et al (2014) with a retrospective cohort design at a national referral hospital in Jakarta showed hypoalbuminemia in the elderly inpatient population with community pneumonia was 71.1% of 142 patients.
A meta-analysis found that for every 10 g/L decrease in serum albumin, mortality increased by 137% and morbidity increased by 89%.Research in 2014 in hospitals in Brazil showed that 9 and 10 elderly patients who were hospitalized experienced a decrease in serum albumin (Brock et al, 2016).In addition, not only reflects the nutritional status of the body, albumin also represents the level of inflammation that occurs (Rosyidi et al. , 2019 ).Decreased albumin levels can be associated with a decrease in the immune system and slow healing of tissues/wounds due to infection.The decrease in the immune system can be seen through indicators in the form of phagocytosis by white blood cells, antimicrobial proteins and the inflammatory response (Hamidin, 2014) .Neutrophils are the first cellular defenses whose numbers increase when inflammation occurs.Research Huang, J (2020) showed that there was a significant correlation between albumin levels and neutrophil inflammation indicators in patients with hypoalbuminemia with Covid-19.Other research shows the condition Hypoalbuminemia that reflects malnutrition results in reduced T lymphocyte activity.According to Aneja (2011), lymphocyte disorders and a decrease in the number of lymphocytes in the circulation and tissues result in organ failure.
Several studies have shown that giving snakehead fish extract ( Channa striata ) in the diet of hypoalbuminemic patients can increase albumin values.Snakehead fish ( Channa striata ) has a very high protein content when compared to other types of freshwater fish (Aisyatusoffi and Abdulgani, 2013).Research by Pratasari, et al (2017) stated that there are 15 types of amino acids found in snakehead fish protein which includes 9 types of essential amino acids.In addition to increasing albumin levels, several studies have shown an effect on the value of neutrophils and lymphocytes.Research by Pettalolo, S. R (2015) showed that there was an increase in the number of lymphocytes in the intervention of supplementing with snakehead fish extract 1500 mg and vitamin C 300 mg for 4 weeks.The potency of Channa striata (ECS) extract has been shown to have great potential in increasing the levels of albumin and amino acids in the blood.
Based on the description of the background, the researcher conducted a literature study on the effect of giving snakehead fish (Channa striata) extract on albumin, neutrophil, and lymphocyte levels in hypoalbuminemic patients.

METHODS
The type and method used is a literature study (Systematic Literature Review or Systematic Review).Database search using Google Scholar , Pubmed, research gate, dan scientists direct.Journals are selected based on inclusion and exclusion criteria, then tested using critical appraisal by following the journal selection stages on the PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analytic ) diagram with the journal selection stages including: identification, screening , eligibility .), and include (enter).

A. Study Characteristics
Based on the search results, there are 10 articles that meet the inclusion criteria related to the topic of the Literature Review.Journals that discuss the effect of giving snakehead fish extract to albumin levels (4 studies), the effect of giving snakehead fish extract to neutrophils (3 studies), the effect of giving snakehead fish extract to lymphocytes (2 studies), and there is one journal that discusses two variables, namely albumin and lymphocyte levels.

B. Characteristics of Respondents
Respondents in this study were patients with hypoalbuminemia and experimental animals.There are more than ten respondents in the study with an average age of 2-75 years, both male and female woman.The results of the characteristics of the respondents can be seen in Table 1.
There are 10 journals studied that show differences in the age characteristics of respondents with the largest frequency of respondents aged 18-75 years.There are 3 out of 10 journals showing that the male gender has the highest hypoalbuminemia compared to the female gender.There are 4 journals using experimental animals, 2 of which show the characteristics of male wistar rats weighing 200-250 grams, and active movement in healthy conditions.Based on 5 journals, patients with hypoalbuminemia occur in elderly patients, nephrotic syndrome, post-surgery, and HIV/AIDS.The average frequency of administration is 14-21 days.This is because albumin is a serum protein synthesized in the liver with a half-life of approximately 21 days (Soemantri, 2009).From 5 journals, the most dominant influence on the nephrotic syndrome group and the most significant increase was the administration of snakehead fish extract at a dose of 2x500 mg/day for 21 days (Muryawan, 2019).This indicates that the greater the dose and duration of administration of snakehead fish extract, the more effective the increase in albumin.Nephrotic syndrome causes the body to lack albumin, so that amino acids from the metabolism of snakehead fish extract are used for albumin synthesis.The level of albumin synthesis in children with nephrotic syndrome is higher than in normal children.The administration of snakehead fish extract containing leucine branded chain amino acid (BCAA) has a unique effect on activating the mammalian target of rapamycin (mTOR) so that it plays a role in ensuring adequate plasma albumin levels.Muryawan's research (2019) is in line with Gilda, G and Heru, M (2015) that serum albumin levels in patients with nephrotic syndrome, the group receiving snakehead fish extract experienced a significant increase.The increase in albumin levels was due to snakehead fish containing essential amino acids and better digestibility compared to vegetable protein because snakehead fish did not contain fiber.Snakehead fish contains amino acids, minerals, vitamins, and fatty acids, therefore various benefits include anti-inflammatory and antioxidant, in addition to acting as a source of protein.
Research by Mulyana, et al. (2017) the effect of giving snakehead fish extract in elderly patients with hypoalbuminemia showed that snakehead fish extract was associated with increased levels of albumin and IGF-1 levels.The elderly are at risk for malnutrition due to dietary restrictions and the catabolic conditions associated with their illness.IGF-1 levels are inversely related to markers of inflammation and oxidative stress and are then positively regulated by specific nutrients such as zinc, magnesium, selenium, along with energy and protein.Administration of snakehead fish extract led to higher levels of IGF-1 thereby reducing inflammation in patients, which may explain the correlation with increased albumin levels.
Research by Rosyidi, et al (2019) in 37 patients there were 12 men and 25 women, most of the patients spent 8-14 days for postoperative control found that preoperative and postoperative serum albumin levels did not have a significant difference.However, postoperative and posttreatment albumin levels had significant differences.Strict perioperative nutritional support and use of immune-modulating formulas have been shown to reduce complications after major surgery and hospitalization.

Table 2. Journal of Extraction Results The Effect of Giving Snakehead Fish Extract on Albumin Levels
No Author and year Frequency of Giving Results

1.
Roza Mulyana, et al (2017) Freeze dried snakehead fish extract 10 grams (2 sachets) for 14 days The results of the study show that there is a significant increase on albumin levels (P=0.003 ) with a mean of 0.5 g/dL.

2.
Geniza G, and Heru Muryawan (2015) VipAlbumin 2 x 150 mg capsules for 14 days The results of the study showed that there was an increase in albumin levels ( p = 0.015) with a mean (0.92±1.105 g/dL ) in the treatment group.

3.
Muhammad Heru Muryawan, et al (2019) EIG supplement 2 x 500 mg for 21 days The results of the study showed that there was an increase in albumin levels (3.6 ± 0.8 g/dL higher than the control 3.2 ± 0.8 g/dL (p<0.05)) 4.

Sri Sustenance Pettalolo (2015)
Pujimin capsules 1500 mg for 4 weeks The results of the study showed an increase in albumin levels in the treatment group (0.5 ± 0.7 g/L) only after administration of snakehead fish and vitamin C.  The results of the study showed a decrease in the number of lymphocytes in the inflammatory phase ( 3.8 ± 2,546 ) with a concentration of 100% 3. Sri Sustenance Pettalolo (2015) Pujimin capsules 1500 mg for 4 weeks The results of the study showed an increase in the number of lymphocytes in the treatment group ( 7.3 ± 12.6% )

D. Effect of Giving Snakehead Fish Extract (Channa striata) on Neutrophil
Based on 3 journals that examined the administration of snakehead fish extract on the value of neutrophils in rats with an inflammatory phase, it showed that there was a significant effect.However, this study has not been able to show its effect on reducing neutrophils in patients with hypoalbuminemia.The structure of the rat liver is similar to that of humans, although human hepatocytes are thicker and well defined than rat hepatocytes, and have a portal triad of v. port, a. Hepatica and bile ducts are similar to humans (Rogers, et al., 2012).So there is a difference in the determination of the dose in humans and mice.Determination of the dose of white rats based on Lawrance & Bacharach (1964) in Fatmawati 2018 by converting the dose that is generally drunk by humans (200 ml) with a conversion factor of 0.018 for mice.
Based on 3 journals, it was found that the average number of neutrophils in rats given 100% snakehead fish extract decreased more.According to Fadhila, et al (2018) that the content of unsaturated fatty acids in snakehead fish extract in the inflammatory phase can regulate postglandin synthesis which acts as a blood vessel vasodilator so that it regulates infiltration, neutrophil activation and can induce healing.This is supported by Sulistiawati (2018) that the more concentration of the active substance given, the more it decreases acute inflammatory cells.
The decrease in the average number of neutrophils in the treatment group of snakehead fish extract 25%, 50% and 100% was due to the presence of compounds in snakehead fish extract such as albumin, unsaturated fatty acids, minerals zinc (Zn), copper (Cu), and iron.(fe) (Agustin, et al, 2016).The content of compounds in snakehead fish acts as an anti-inflammatory effect that can increase albumin levels and reduce the number of neutrophils in hypoalbuminemia who are injured.Taslim et al (2022) research on hyperglycemic rats with wounds showed that the intervention group on day 10 experienced a decrease in neutrophils and an increase in albumin and lymphocyte values.A decrease in the percentage of neutrophils occurs when there is a decrease in the signal from the proinflammatory sticonyl-17 that suppresses its production in the bone marrow.An increase in albumin indicates that the body can resume its physiological function of synthesizing albumin when inflammation is reduced.

E. Effect of Giving Snakehead Fish Extract (Channa striata) on Lymphocytes
Decreased albumin levels can be associated with a decrease in the immune system and slow healing of tissues/wounds due to infection.Snakehead fish extract contains essential amino acids and as a source of antioxidants, where food sources of antioxidants are part of the components of the immune system.Research by Kasim, et al (2017) the addition of extract snakehead fish in the intervention group had an effect greater effect on the decrease in TNFα value, so it can be said that the effect of the amino acids contained in the supplement can activate T lymphocyte cells to inhibit various functions of activated macrophages.Giving snakehead fish extract dose 3x2 for 14 days showed that the immune function test by calculating TLC, got significantly different results between the intervention group and the control group (p=0.034) with an average increase before and after the intervention in the intervention group of 990.54 cells./mm.Izzaty, et al (2014) showed that the extract of haruan or snakehead fish could reduce the number of inflammatory phase lymphocytes in the healing process of the buccal mucosa of wistar rats with the best concentration of The content of albumin, Zn, Fe, Cu and unsaturated fatty acids are useful in reducing inflammation.Low albumin can cause low blood osmotic pressure, resulting in fluid seepage in the blood vessels .Therefore, the administration of snakehead fish extract is quite effective in giving hypoalbuminemia patients with inflammatory conditions, sepsis, and several other diseases to reduce the number of lymphocytes in the body when it increases.

Research by
Research by Pettalolo, S. R (2015) conducted an intervention in providing supplements of snakehead fish extract 1500 mg and vitamin C 300 mg for 4 weeks in 36 HIV/AIDS patients, including 5 patients with hypoalbuminemia.The increase in the number of lymphocytes in the snakehead fish extract group was associated with the presence of zinc which is known to affect immune function, restore the organism's immunity by increasing the activity of the catalase enzyme and superoxide dismutase (SOD) enzyme, then increasing the production of lymphokines, causing lymphocyte cells to be able to differentiate and proliferate.

CONCLUSIONS
The content of amino acids, albumin, Zn, Fe, Cu and unsaturated fatty acids in snakehead fish ( Ophiocephalus striatus) is quite effective as an effort to increase albumin levels, decrease neutrophil and lymphocyte values when inflammation occurs in hypoalbuminemic patients.
1. Giving snakehead fish ( Channa striata ) extract at a dose of 2x500 mg for 21 days is quite effective as an effort to increase albumin levels in hypoalbuminemic patients.2. The administration of snakehead fish ( Channa striata ) extract is quite effective as an effort to reduce the neutrophil value with a concentration of 100% in wistar rats, but has not shown any effect on hypoalbuminemic patients.
3. Giving snakehead fish ( Channa striata ) extract at a dose of 1500 mg for 4 weeks is quite effective as an effort to reduce lymphocyte values during inflammation and increase lymphocyte values in hypoalbuminemic patients.

Table 1 .
Characteristics of Respondents