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Medicine
DOI: 10.21070/acopen.10.2025.10941
Published: 2025-05-11

Evaluation of the Effect of Acrylamide and Furfural on Some Biochemical and Liver Histological Variables in Adult Male Albino Mice


Evaluasi Pengaruh Akrilamida dan Furfural terhadap Beberapa Variabel Biokimia dan Histologi Hati pada Tikus Albino Jantan Dewasa

Department of Biology, Collage of education , University of Samarra
Iraq
Department of Biology, Collage of education , University of Samarra,
Iraq

(*) Corresponding Author

Acrylamide liver tissues Furfural liver function

Abstract

General Background: The liver plays a critical role in metabolism and detoxification, processing substances such as acrylamide and furfural, which are commonly present in heat-processed foods. Specific Background: Acrylamide, formed during the cooking of starchy foods, is metabolized in the liver to glycidamide, a highly reactive compound. Furfural, found in various heat-processed foods, can also negatively impact liver health. Knowledge Gap: Limited research has investigated the comparative effects of acrylamide and furfural on liver function and histology. Aims: This study aimed to evaluate the biochemical and histological effects of acrylamide and furfural on liver function in adult male albino mice. Results: The results revealed significant alterations in lipid profiles, including increased HDL and VLDL levels, as well as histopathological damage such as hepatocyte hypertrophy, leukocyte infiltration, and necrosis. Elevated liver enzyme levels (ALT, AST, ALP) indicated compromised liver function. Novelty: This study provides novel insights into the comparative toxicity of acrylamide and furfural on liver tissue and function. Implications: The findings suggest that prolonged exposure to acrylamide and furfural may induce oxidative stress and liver disease. Further research is needed to explore protective interventions and inform regulatory policies regarding exposure limits to these compounds.

Highlights:

  1. Hepatoprotective Effect: Astaxanthin reduces diazinon-induced liver damage in rats.

  2. Dose-Dependent: 100 mg/kg astaxanthin shows strongest protective effects.

  3. Mechanism: Reduces oxidative stress, inflammation, and liver enzyme levels.

Keywords : Acrylamide, liver tissues , Furfural, liver function .

Introduction

The liver is one of the largest glands in the body and a vital organ with essential functions during fetal life and after birth. The liver consists of complex metabolic cells containing high levels of several enzymes essential for carrying out metabolic reactions. In the event of damage to the cell membrane or its organelles, these enzymes leak into the extracellular space and are then released into the blood. This process occurs very quickly, as the activity of enzymes in the blood increases. This activity can be measured within hours of the injury. This increase can be used to diagnose and monitor structural and functional disorders of the liver. Knowing the cellular localization of enzymes explains the identification of several pathological conditions (1, 2).

The cytoplasm of hepatocytes contains the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and Alkaline phosphate (ALP). These enzymes are present in high concentrations in the liver and are used as a diagnostic criterion in liver disease (3,4), Most cases of acute liver injury often result in elevated liver enzyme levels within 24-48 hours of the injury, while chronic hepatitis is usually diagnosed by elevated liver cytoplasmic enzyme levels (5,6).

The liver is affected by all substances entering the body, including acrylamide, a chemical that forms naturally in starchy foods during cooking or processing at high temperatures, such as frying, baking, or roasting. This substance has raised global concern due to its potential negative effects on human health. The liver is the main organ in which acrylamide is metabolized and eliminated. When acrylamide enters the body, it is converted in the liver into a more reactive compound called glycidamide. Glycidamide is largely responsible for the toxicity caused by acrylamide, including effects on the liver (7).

Furfural, an organic chemical compound naturally occurring in small amounts in some heat-processed foods such as bread, breakfast cereals, honey, and fruits, also affects liver function. Some studies indicate that consuming high amounts of furfural can cause damage to liver tissue. Several laboratory animal studies have shown a relationship between furfural intake and changes in liver enzyme concentrations and the formation of some tumor cells (8).

Furfural is metabolized in cells. The liver produces secondary metabolites that may have effects on liver tissue cells. Consuming large doses of furfural significantly affects the functions and structure of liver cells (9,10).

Therefore, this study aimed to evaluate the effects of acrylamide and furfural on histology and some biochemical variables related to liver function in adult male albino mice.

Methods

-The Experimental Animals :

This experiment used (40) adult male white mice, aged (2 - 3) months and weighing between (25 - 26) gm, The study was conducted in December 2024 for 30 days. The animals were raised in a special room with the correct conditions for animal husbandry, including feeding, temperature, lighting, and ventilation, in the laboratories of the Pharmacology Department of the General Company for Pharmaceutical Industries in Samarra, The animals were divided into five groups, with (8) animals per group, and were treated for 30 days as follows:

G1: They were given regular drinking water and standard feed throughout the experiment and were considered the control group.

G2: Acrylamide was administered at a concentration of 15 mg/kg of body weight dissolved in distilled water, and the animals were given a daily dose of 0.1 ml orally for 30 days.

G3: Acrylamide was administered at a concentration of 30 mg/kg of body weight dissolved in distilled water, and the animals were given a daily dose of 0.2 ml orally for 30 days.

G4: Furfural was administered at a concentration of 50 mg/kg of body weight dissolved in distilled water, and the animals were given a daily dose of 0.1 ml orally for 30 days.

G5: Furfural was administered at a concentration of 100 mg/kg of body weight dissolved in distilled water, and the animals were given a daily dose of 0.2 ml orally for 30 days.

-Blood Sample Collection :

After the end of the specified experimental period (30) days, the animals were dissected and blood was drawn directly from the heart using a medical syringe with a capacity of (3) cm3, as approximately (2-3) ml of blood was drawn and placed in test tubes free of anticoagulant and left at room temperature for 20 minutes until the blood clotted, and then it was centrifuged at a speed of 3000 rpm for 15 minutes for the purpose of obtaining blood serum, and the serum was kept frozen at -20 degrees Celsius until the biochemical tests scheduled for this study were carried out.

-Biochemical analysis:

The concentrations of ( VLDL, HDL, LDL, ALT, AST, and ALP) were measured by followed the procedure that given with kit (Biolabo-France) .

-Obtaining tissue samples :

After the experiment was completed, the animals were slaughtered. Liver samples of 0.5 cm3 were taken and placed in 10% formalin for (12) hours. After washing with water for (10) minutes, a series of tissue passes were performed on them using alcohol and xylene, followed by impregnation and embedding in paraffin wax. Special L-shaped molds were made using clean paraffin wax with a melting point of 60°C. They were then cut using a rotary section with a thickness of 4-5 microns. The sections were surfaced with 30% alcohol and then transferred to a special water bath for sectioning at a temperature of 45°C. They were then placed on glass slides to prepare them for staining, as they were stained with (H & E) stain according to (11)They were then examined under a light microscope and photographed to evaluate the changes that occurred in the liver tissue.

-Statistical Analysis :

The results were statistically analyzed using the Statistical Analysis Package for Social Science (SPSS) to extract significant differences between the experimental groups, confirming these differences by extracting the standard deviation (SD). Statistical analyses were conducted at a significance level (P≤0.05) according to (12)

Result and Discussion

-Results of Biochemical analysis:

The results of the statistical analysis included in Table (1) show a significant increase at the significance level P ≤ (0.05) in HDL, VLDL and ALP in the blood serum of the treated groups when compared to the control group, While There was a significant decrease in concentration of AST and ALT in the treated groups when compared to the control group.

FurfuralM ± SD100 mg /kg)) FurfuralM ± SD50 mg /kg)) AcrylamideM ± SD30 mg /kg)) AcrylamideM ± SD15 mg /kg)) ControlM ± SD GroupsParameter
36.90 ±12.57c 44.33 ±13.50ab 47.43 ± 12.16 a 42.39 ± 10.68b 21.89 ± 1.191d HDL( dl/ mg)
13.73 ±1.95c 16.05 ± 2.17ab 18.11 ± 2,82a 17.32 ± 3.30 ab 15.80 ± 3.60bc VLDL( dl/ mg)
6.28 ±1.79bc 6.71 ± 0.75b 5.42 ±1.90cd 5.28 ± 1.38 d 7.42± 1.18a ALT
16.43 ±3.69c 19.42 ± 1.27b 12.86 ± 3.02d 18.14 ± 1.06 bc 25.4 ± 4.64 a AST
10.38 ±1.00b 9.95 ± 0.26 bc 11.11 ± 0.89a 11.31±1.25a 9.47 ± 0.75 c ALP
Table 1.Shows the values ​​of biochemical variables for the study groups.

* Different lowercase letters horizontally indicate significant differences at the level of P≤0.05

The results of the statistical analysis showed a significant increase in the concentration of high-density lipoproteins in the group treated with acrylamide 15 and 30 (mg /Kg) ,when compared to the control group. This may be due to the occurrence of liver cirrhosis, fatty accumulation in the arteries, and an increased risk of fatty liver disease. Some recent studies indicate that high levels of HDL increase the risk of cardiovascular disease in some cases, and thus agree with (13) High-density lipoprotein (HDL) concentrations were also elevated in the furfural 50 and 100 (mg /Kg)treated groups. Although there is no direct relationship between this compound and blood lipids, this may be due to lipid accumulation and loss of hepatocyte cellular structure, which in turn affects the liver's lipid metabolism pathway as, in study (14)

The results of the statistical analysis showed a significant increase in the concentration of very low-density lipoprotein (VLDL) in the acrylamide-treated groups when compared to the control group. This may be due to the possibility of insulin resistance, which leads to elevated triglyceride levels, or the development of metabolic syndrome, which may affect thyroid production and hypothyroidism. Hypothyroidism can slow fat metabolism, which may lead to elevated VLDL levels. It may also be due to the development of non-alcoholic fatty liver disease, this agree with (15), and Very low-density lipoprotein (VLDL) concentrations also increased in the furfural-treated groups compared to the control group, possibly due to oxidative stress and activation of inflammatory pathways that damage liver cells, the primary organ responsible for producing triglycerides. Some animal research suggests that exposure to high doses of furfural may affect liver function, as in (16)

.While the results of the statistical analysis showed a significant decrease in the concentration of the ALT and AST enzyme in the groups treated with acrylamide compared to the control group, this may be due to the negative impact on the digestive system, which consequently affects the health of digestion and absorption, leading to a deficiency of many vitamins and an impact on nerve signals and cellular receptors lining the intestinal lining. This impacts the morphological structure of the intestine, resulting in interference with nutrient concentrations that negatively impact the production of liver enzymes. This is agree with (17) While the results of the statistical analysis showed a significant decrease in the concentration of the ALT and AST enzyme in the groups treated with furfural when compared to the control group, this may be due to the occurrence of cases of oxidative stress in the cells of the intestinal lining and an increase in the concentration of free radicals and thus a deficiency in the formation of many vitamins, such as B6 those that are one of the factors affecting the formation of enzymes, which leads to a defect in the functional processes of liver cells and interference in the concentration of nutrients that negatively affect the production of liver enzymes, This is agree with (18), Alkaline phosphatase (ALP) is an enzyme found throughout the body. Its production may increase in several pathological conditions, including inflammation and obstruction of the bile duct and liver duct, the occurrence of liver cirrhosis and fatty liver disease, and thus the enzyme leaks into the bloodstream. It may occur under the influence of hyper production of thyroid hormones, this agree with ( 19).

-Results of Histological study(Liver tissues):

G1- Control group:

The liver tissue in the control group appeared normal, containing a central vein surrounded by polygonal liver cell clusters with large, dark-staining central nuclei arranged in radial rows. Sinusoids containing Kupffer cells were also present, as in image (1, a). Meanwhile, the liver parenchyma in the portal area contained a portal vein branch, bile duct branches, and lymphatic duct branches. These structures were surrounded by white blood cells and sinusoids containing Kupffer cells, as in image (1, b).

Figure 1.a): A section of the liver in the control group: showing the central vein (A), polygonal hepatocytes with spherical nuclei (B), blood sinusoids containing Kupffer cells (C), (H&E), (X400). b): Section of the liver in the control group: showing the central vein (A), bile duct (B), lymphatic vessel (C), large cell aggregates (D), leukocyte infiltration in the portal area (E), blood sinusoids (F), (H&E), (X400).

G2 - The group treated with acrylamide (15 mg/kg):

The liver tissue appeared to contain a wide-bore central vein containing hemolysis blood and lipid droplets in the vein's lumen. White blood cells were found around the vein. Liver cells were polygonal in shape, hypertrophic, and had large, dark-stained central nuclei. These cells were arranged in radial rows. Blood sinusoids appeared, containing a large number of Kupffer cells, as shown in Figure (2,a). Meanwhile, the liver parenchyma appeared to contain enlarged cells, some of which had lost their nuclei, and some had degeneration of the cytoplasm. The structures were surrounded by white blood cells and blood sinusoids containing excessive Kupffer cells. Hyperplasia also occurred in the sinusoids, as shown in Figure (2,b).

Figure 2.a) :A section of the liver from the 15 mg/kg acrylamide-treated group: showing hemolysis in central vein (A), lipid droplets (B), lymphatic vessels (C), large cell aggregates (D), leukocyte infiltration in the portal area (E), and blood sinusoids (F), ( H&E ), (x400). b): A section of the liver from the 15 mg/kg acrylamide-treated group: hypertrophy of hepatocytes (A), a nuclear hepatocytes (B), portal lymphocytes (C), and hyperplasia (D), (H&E) (x400).

Liver sections in the acrylamide (15mg/kg) showed enlarged, lipid-containing droplets, which may be due to oxidative stress resulting from acrylamide-induced liver toxicity and damage (20). Acrylamide increases the formation of free radicals and reactive oxygen species (ROS), leading to hepatocyte damage due to lipid peroxidation and DNA damage (21), Some areas also showed leukocyte infiltration, indicating inflammatory responses in the liver due to the acrylamide dose. This leads to the production of inflammatory cytokines such as TNF-a, IL-10, and IL-6, activation of the NF-KB pathway, and activation of apoptosis, which contributes to liver tissue damage. Acrylamide causes structural tissue changes, including vacuolar degeneration of hepatocytes, necrosis, disruption of liver sinusoids, infiltration of inflammatory cells, and vascular fibrosis, as (22)

G3- The group treated with acrylamide (30 mg/kg):

Liver tissue appeared enlarged, with cells appearing compact and lacking clear cell boundaries. Hepatocytes also appeared pale and had nuclei devoid of pigment. Blood sinusoids containing a large number of Kupffer cells were present, and some cells appeared enlarged, as shown in Figure (3,a). Meanwhile, the central vein of the liver appeared to contain hemolysis blood, surrounded by white blood cells and very narrow blood sinusoids containing Kupffer cells. Hyperplasia also occurred in some hepatocytes, as shown in Figure (3,b).

Figure 3.a): A section of the liver in the group treated with acrylamide (30 mg/kg): Hepatocyte hyperplasia appears compact (A), pigmentation disappears in the nuclei of the cells (B), blood sinusoids containing Kupffer cells (C), hemolysis blood in the central vein (D), and focal lymphocytic accumulation. (E), (H&E ),( 400x). b): A section of the liver from the 30 mg/kg : central vein containing hemolytic blood (A), leukocyte infiltration around its wall (B), hypertrophy of hepatocytes (C), loss of nuclei in some hepatocytes (D), and sinusoids containing some Kupffer cells (E), (H&E) , (400x) .

Liver sections in the acrylamide-treated group of mice showed leukocyte infiltration, indicating inflammation in the liver tissue. White blood cells migrate from the capillaries to the site of injury or infection as a response to the immune system. The presence of lymphocytes is indicative of autoimmune diseases (23). Hepatocyte enlargement may indicate that the liver is overworked and working harder to remove toxins or certain molecules ( 24). It may also be due to hepatocytes adapting to compensate for the damage or loss of other hepatocytes. The accumulation of fat (steatosis) or glycogen may also lead to hepatocyte enlargement ( 25). Loss of nuclei (nucleolysis) or rupture of the nucleus followed by its disappearance) is a sign of cell death, specifically necrosis. Necrosis is often associated with inflammation and tissue damage as (26)

G4- The group treated with furfural (50 mg/kg):

The liver tissue appeared enlarged, with spherical nuclei, each nucleus composed of multiple nuclei. The sinusoids contained a large number of large Kupffer cells. The central vein appeared devoid of blood, with its ends connected to the sinusoids, as in image (4,a). Meanwhile, the central vein of the liver appeared devoid of blood, its outer wall surrounded by large numbers of white blood cells and hypertrophied hepatocytes, tightly packed and with blurred borders, and pale, spherical nuclei. Kupffer cells were also present within the narrow sinusoids, as in image (4,b).

Figure 4.a): Section of the liver in the group of furfural (50 mg/kg): hyperplasia of hepatocytes (A), narrow sinusoids containing Kupffer cells (B), central vein free of blood (C), (H&E), (X400). b) Section of the liver in the group of furfural (50 mg/kg): central vein free of blood (A), infiltration of white blood cells around the vein (B), hypertrophy of hepatocytes (C), Kupffer cells in the sinusoids (D), (H&E), (X400).

Histological examination of liver sections in the furfural (50 mg/kg) showed infiltration of white blood cells around the central vein, which may indicate inflammation in liver tissue cells, Hepatocyte hyperplasia was also evident, meaning that the liver cells are larger than normal, Hepatocyte hyperplasia is a common response to various forms of liver injury or metabolic stress. It can occur when the liver is working harder to metabolize substances or when there is cellular damage and repair. Kupffer cells, which are resident macrophages (immune cells), also accumulated within the hepatic sinusoids (small blood channels in the liver). The presence of Kupffer cells is normal in liver tissue, but their large and increased activity indicates an immune response to inflammatory conditions, this study agree with (27),

G5- The group treated with furfural (100 mg/kg):

Liver tissue appeared to contain a large number of white blood cells and macrophages around the central vein, as well as some enlarged tumor cells with aneuploidy nuclei and cytoplasmic vacuolation, as shown in Figure (5,a). Meanwhile, the central vein of the liver appeared to have a wide lumen, containing a small blood clot and communicating with the blood sinusoids. White blood cells and macrophages were found within the lumen of the central vein. Hepatocytes were hypertrophied and compact, in addition to the presence of Kupffer cells, some of which appeared enlarged, as shown in Figure (5,b).

Figure 5.a): Section of the liver in the group of furfural (100 mg/kg): The central vein contained hemolysis blood and lipid droplets (A), infiltrated white blood cells (B), tumor cells (C), and inflammatory cells (D), (H&E ) (x400). b): Section of the liver in the group of furfural (100 mg/kg): the central vein is wide and contains a blood clot (A), infiltration of white blood cells and lymphocytes (B), hyperplasia of hepatocytes (C), Kupffer cells in the blood sinusoids (D), (H&E), (X400).

Histological examination of Section of the liver in the group of furfural (100 mg/kg) revealed a blood clot (thrombus) within a blood vessel in the liver tissue, indicating a disruption of normal blood flow, resulting in hypoxia or tissue death in the area supplied by the vein, (28) The infiltration of white blood cells, specifically lymphocytes, indicates an inflammatory response, as lymphocytes play a key role in adaptive immunity. The total number and types of white blood cells present can provide additional clues about the nature of the inflammation, (29) Hepatocyte hyperplasia may indicate an increase in the number of hepatocytes, as opposed to hyperplasia, which is an increase in their size. Hepatocyte hyperplasia often occurs as a regenerative response to liver injury; it indicates that the liver is attempting to repair damaged tissue by producing more hepatocytes (30).

Conclusion

In conclusion, the biochemical and histological analyses of liver tissues in this study revealed significant alterations in lipid profiles and liver cell morphology following treatment with acrylamide and furfural. Specifically, the treated groups exhibited increased concentrations of HDL and VLDL, indicative of potential disturbances in lipid metabolism and liver function, alongside marked histopathological changes such as hepatocyte hypertrophy, leukocyte infiltration, and hepatocyte necrosis. These findings suggest that acrylamide and furfural may induce oxidative stress, inflammation, and metabolic disruptions in liver cells, which could contribute to the development of liver disease, including fatty liver and cirrhosis. The observed alterations in liver enzyme levels (ALT, AST, ALP) further support the notion of compromised hepatic function. The results underline the need for continued investigation into the long-term effects of these compounds on liver health and the mechanisms underlying their toxicity. Further research should explore potential protective interventions, as well as the dose-dependent effects of these chemicals on liver function and pathology, to better inform public health policies and regulatory frameworks regarding exposure limits.

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