Research Article

Protective Effect of Selenium Against Arsenic-Induced

Hematological, Biochemical Alteration, and Organ Development Anomalies in Adult Female Mice

Md. Khayrul Basher1, Sumon Sarkar2,3, Md. Samiul Haque1, Sourav Sarker4, Md. Rashedul Islam1*

1Department of Genetics and Animal Breeding, Faculty of Veterinary and Animal Science, Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh; 2Department of Physiology and Pharmacology, Faculty of Veterinary and Animal Science, Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh; 3School of Veterinary Medicine, Texas Tech University, 7671 Evans Dr., Amarillo, TX 79106, USA; 4Green Life Medical College, MAK Khan Tower 30, Bir Uttam K.M. Shafiullah Sarak, Green Rd, Dhaka 1205, Bangladesh.

Received | January 01, 2024; Accepted | February 22, 2024; Published | April 26, 2024

*Correspondence | Md. Rashedul Islam, Department of Genetics and Animal Breeding, Faculty of Veterinary and Animal Science, Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh; Email: [email protected]

Citation | Basher MK, Sarkar S, Haque MS, Sarker S, Islam MR (2024). Protective effect of selenium against arsenic-induced hematological, biochemical alteration, and organ development anomalies in adult female mice. Adv. Anim. Vet. Sci., 12(6):1107-1116.

DOI | https://dx.doi.org/10.17582/journal.aavs/2024/12.6.1107.1116

ISSN (Online) | 2307-8316

Copyright: 2024 by the authors. Licensee ResearchersLinks Ltd, England, UK.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

INTRODUCTION

Arsenic is widely distributed in the environment and is emitted by both natural and man-made activities (Rahman et al., 2018). Due to the drinking of tainted groundwater, a significant amount of people in Bangladesh and other countries are under threat of arsenic exposure (Barai et al., 2017; Paul, 2006). It is well acknowledged that arsenic poisoning is a serious worldwide health concern. The World Health Organization (WHO) states that the acceptable arsenic level in drinking water has lowered from 50 micro g/l to 10 micro g/l. However, the amount of arsenic and arsenic-induced toxicity is gradually rising, and pollution from natural sources in various geographically remote parts of the world can reach hundreds of micrograms per liter. Arsenic’s rising environmental toxicity is concerning and poses a serious risk to the general public’s health worldwide. Eating and drinking, inhalation, and cutaneous absorption are the most frequent sources of arsenic exposure (Halder et al., 2013; Palma-Lara et al., 2020; Sun et al., 2014). In addition to the increased risk of several cancers (Liu et al., 2013), long-term arsenic exposure has also been linked to non-cancerous health risks such as diabetes, skin conditions, cardiovascular disease, neurological toxicity, and toxic effects on the liver, lung, kidney, spleen, and heart (Basher et al., 2023; Karagas et al., 2015; Khatun et al., 2020; Mao et al., 2016; States et al., 2009). Arsenic poisoning is thought to occur through several different pathways, such as the creation of oxidative stress, the inhibition of enzymes, and alterations in mitochondrial function (Flora et al., 2007).

Arsenic poisoning has been shown to alter the concentration of liver enzymes, according to experimental research on the liver, which is the organ most susceptible to arsenic damage. Specifically, oxidative stress and ROS generation are linked to liver damage (Das et al., 2012). The liver is the primary organ involved in metabolism inside the body and is most affected by arsenic intoxication. Chronic exposure to arsenic leads to symptoms such as liver enlargement (hepatomegaly), cirrhosis, and impaired liver enzyme activity in affected individuals (Liu and Waalkes, 2008). Analyses of biochemistry, hematology, and histopathology may be used to assess the toxicant’s mode of action since they can assist predict important sub-lethal effects. Hematological and biochemical examinations of blood parameters are crucial for determining the structural and functional condition of a person exposed to a toxin (Al-Forkan et al., 2016).

Arsenic-induced oxidative stress is the most common and widely accepted method of arsenic intoxication. Reactive oxygen species are created because of oxidative stress by interacting with sulfhydryl groups which leads to the inhibition of numerous enzymes like DNA repair enzymes and antioxidant-related enzymes (thioredoxin reductase and glutathione peroxidase) (Ganyc et al., 2007; Pi et al., 2002; Ruiz-Ramos et al., 2009). These arsenic-generated reactive species cause oxidative stress to rise in cells, which in turn causes oxidative DNA damage and apoptosis (Yedjou et al., 2010). Many studies have shown that this oxidative stress is capable of interfering with several cellular signaling pathways that may be crucial in the manifestation of an arsenic-mediated illness (Druwe and Vaillancourt, 2010; Sumi et al., 2010). Despite arsenic poisoning being recognized as a hazard to worldwide public health, most of its effective, trustworthy, and safe treatments are still unknown. Recent research has shown that antioxidants may have a role in the management or prevention of arsenic poisoning (Rahman et al., 2018; Shathy et al., 2020; Yu et al., 2016).

Selenium is a crucial antioxidant with possible cancer-prevention and chemoprotective properties (Patrick, 2004). Mammals have been examined for the antioxidant functions of selenium at low concentrations (Sun et al., 2001). It is a part of several selenoproteins, including those with crucial biological activities such as glutathione peroxidases and thioredoxin reductases. The antioxidant and detoxifying properties of these selenoproteins are well established. Numerous hypothesized mechanisms for selenium’s chemoprotective properties have been put forth, including oxidant defense, altered carcinogen metabolism, improved immune surveillance, apoptosis modulation, and angiogenesis suppression (Letavayová et al., 2008; Zeng et al., 2005). Selenium has been shown to have protective and advantageous effects on mammals (Xue et al., 2010). The following cellular levels have shown that selenium has protective effects against arsenic toxicity: cultured human leukemia HI-I-60 cells (Zeng, 2001; Zwolak, 2020), human hepatocytes (Walton et al., 2003), and the A375 cell line (Wang and Guo, 2011).

Due to unavoidable exposure to arsenic, the mitigation of its toxicity is now a significant global research challenge. There is a great deal of understanding about selenium’s antioxidant and protective abilities, but nothing is known about how it could lessen the toxicity caused by arsenic. There are notably few studies on the protective effects of selenium against arsenic-caused hematological, biochemical, and organ development issues in both people and animals. It is crucial to investigate how sodium selenite protects against sodium arsenite-induced anomalies given the biological relevance of selenium and arsenic coexisting in the environment as well as their prevalence in anthropogenic discharges. The complicated interaction between arsenic and selenium can have both antagonistic and synergistic effects when taken together. Through altering cytotoxicity, genotoxicity, and oxidative stress, selenium can reduce arsenic toxicity in both vivo and vitro (Chitta et al., 2013; Jamwal and Niyogi, 2017; Ponomarenko et al., 2017; Sah et al., 2013; Selvaraj et al., 2012). Therefore, this study hypothesizes that co-exposure to selenium may mitigate the hematological, biochemical, and organ development abnormalities caused by arsenic in adult female mice. As a result, the goal of this study for the first time was to investigate the protective potential of sodium selenite on hematological, biochemical, and organ development anomalies in sodium arsenite-exposed adult female mice.

MATERIALS AND METHODS

Selection and maintenance of the lab animals

Swiss albino female mice, aged 4-5 weeks, were procured from the International Center for Diarrheal Disease Research, Bangladesh (icddr, b). Four mice per cage were randomly selected and placed in plastic cages with wood-cob bedding. and were reared at 23±2℃, maintaining 12 hours of a light-dark cycle in a well-ventilated, humidified room with proper feed and water supply at the laboratory animal facilities of the Department of Genetics and Animal Breeding at Hajee Mohammad Danesh Science and Technology University. Every other day, drinking water was changed to avoid arsenic oxidation. All the procedures and animal experiments using mice were commenced after prior approval and following the rules and regulations set by the laboratory animal ethics committee of the Institute of Research and Training (IRT), Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh.

Ethical approval statement

This research project has been approved by the animal ethics committee of the Department of Genetics and Animal Breeding at Hajee Mohammad Danesh Science and Technology University in Bangladesh at meeting resolution number 09, which was held on July 12, 2022, because the experimental design of the study was not objectionable or subversive to animal ethics.

Design of the experiment

For this experiment, 24 mice were selected at random and categorized into four groups (6 mice in each group), namely Group-I (control), Group-II (sodium arsenite-NaAsO2), Group-III (sodium arsenite-NaAsO2 plus sodium selenite-Na2SeO3), and Group-IV (sodium selenite-Na2SeO3). From the age of 8–9 weeks, treatment started accordingly and immediately. Mice from Group I were given only normal drinking water. Group (II) and Group (IV) mice were given 10 micromolar of sodium arsenite (NaAsO2; Sigma-Aldrich, USA) and 10 micromolar Sodium selenite (Na2SeO3; Sigma-Aldrich, USA) (Cho et al., 2023; Jeong et al., 2023; Shi et al., 2013) dissolved in deionized distilled water (ddH2O), and a combination of 10 micromolar of sodium arsenite and sodium selenite was given to the mice of Group (III) mice through drinking water for 60 days.

Collection and processing of samples

After 60 days of the treatment period, adult female mice were euthanized using light diethyl ether (W509043, Sigma-Aldrich, St. Louis, MI, USA) anaesthesia after overnight fasting. By the heart puncher, blood was quickly collected for a significant volume in a collecting tube for hematological and biochemical analysis. Different organs, namely the liver, lungs, kidney, spleen, heart, and uterus, were carefully removed for the analysis of organ morphology and organ-to-body weight ratio.

Hematological assessment

Lithium heparinized tubes (BD 36666; Thermo Fisher, Waltham, Massachusetts, USA) was used to collect the blood samples, and a complete blood count (CBC) was performed for these samples to determine the hematological parameters such as the estimation of red blood cells, white blood cells, platelets, hemoglobin, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), differential leukocyte count (DLC), and others by using an automatic whole blood analyzer (BC-20; Mindray, Shenzhen, P.R. China). Hematological parameters were evaluated among different treatment groups. 

Biochemical analysis

Clot activator tubes were used to collect blood samples for biochemical evaluation. After clotting, the blood samples were properly centrifuged (for 10 minutes at 6000 rpm) for the collection of serum (using a pipette). To analyze random blood sugar (RBS), alkaline transaminase (ALT), alkaline phosphatase (ALP), triglyceride, total cholesterol, and uric acid, a biochemical analyzer (18200; HUMAN, Wiesbaden, Germany) and commercially available reagent (RANDOX, Crumlin, County Antrim, United Kingdom) according to the manufacturer’s protocol were used. Biochemical parameters were evaluated among different treatment groups.

Body weight and organ weight measurements of mice

Every day, an analytical balance was used to weigh and record each mouse in each group. The abdomen was surgically exposed by a ventral incision after 8 weeks of maintenance. The liver, lung, heart, kidney, spleen, and uterus were meticulously removed, thoroughly cleansed of all fat and connective tissue, and weighed. The organ-to-body weight ratio was then calculated by the following formula: (organ weight/body weight) ×100% and compared among different groups.

Gross morphology of vital organs

The visualization of different vital organs like the liver, lungs, spleen, heart, kidney, and uterus was evaluated according to size, shape, color, and consistency to understand the adverse effect of arsenic and the protective properties of selenium on organ development. A centimeter scale was used to determine the size of the organs and to take a clear photo on color paper for easy differentiation and comparison among the four groups.

Statistical analysis

A minimum of three repetitions were run through each experiment. As a ratio to each control, the results are shown as mean ± SEM. The statistical differences were examined using a single-factor analysis of variance (ANOVA). Analysis of Variance, or ANOVA, is a statistical test that examines how the means of more than two groups differ from one another. One independent variable is used in a one-way ANOVA, with significance set at p<0.05. The student-Newman-Keuls test was additionally utilized to compare the two groups, this test is step-by-step multiple comparison technique to determine which sample means differ significantly from one another. When differences reached a p-value of 0.05, they were deemed significant. Differences were considered significant at the level of p<0.05.

RESULTS and Discussion

Potential role of sodium selenite in recovering Hematological aberrations induced by sodium arsenite

Hematological alterations were found due to sodium arsenite exposure. The current study evaluates the ameliorative effect of selenium on hematological status. The values of hematological parameters are presented in Table 1. The results revealed that sodium arsenite caused a significant (p<0.05, respectively) increase in total WBC (white blood cell) count, RBC (Red blood cell) count, platelet count, Hb (hemoglobin concentration), ESR, TCE, PCV%, and RDW SD (red blood cell dimension width-standard deviation) compared to the control (Table 1). But interestingly, when the sodium arsenite (NaAsO2) was exposed, adult female mice were supplemented with sodium selenite (Na2SeO3) at the same concentration in the NaAsO2+Na2SeO3 group, significantly (p<0.05, respectively) reduced than the Na-arsenite (NaAsO2) group of mice (Table 1). A similar trend is found among the groups for neutrophils, eosinophils, lymphocytes, and monocytes (Table 1).

Na-selenite (Na2SeO3) improves Na-arsenite (NaAsO2) induced biochemical abnormalities

The impact of arsenic exposure on the serum biochemical levels in mice is depicted in (Table 2). The liver is regarded as one of the most crucial organs in the body because of its capacity to metabolize nutrients, cleanse dangerous chemicals, and carry out a variety of other essential tasks. ALP and ALT levels were tested since it is known that higher activity of these enzymes is associated with

 

Table 1: Hematological parameters of Mice with different treatment group.

Parameters	Treatments
	Control	NaAsO2	NaAsO2+Na2SeO3	Na2SeO3
TC of WBC (/cmm)	4400±84.11	7000±115.47a	4223.33±14.52*	4800±43.30b**$
Neutrophils (%)	3±0.11	5±0.15a	7±0.05b*	5±0.1c$
Lymphocytes (%)	90±1.52	86±0.57	85±0.57a	87±0.57
EosinoPhils (%)	3±0.11	4±0.1a	3±0.05*	3±0.05**
Monocytes (%)	4±0.11	5±0.05a	5±0.05b	5±0.05c
HB (g/dl)	11.4±0.30	14.1±0.1a	13.5±0.05b*	13.8±0.05c$
ESR (mm in 1st hour)	6±0.57	4±0.05a	4±0.05b	3±0.05c*$
TCE (/cmm)	132±0.57	280±6.42a	126±0.57b*	144±0.57c**$
Platelet count (/cmm)	653000±1000	1133000.33±1157.88a	579000±563.47b*	758000±556.77c**$
RBC count (million/cmm)	7.05±0.07	9.11±0.00a	8.63±0.01b*	9.56±0.03c**$
PCV (%)	38±0.57	47±0.57a	45±0.28b*	46±0.52c
MCV (fl)	47.4±0.55	49.1±0.60	48.2±0.15	47.1±0.20*$
MCH (Pg)	16.1±0.20	16.4±0.26	16.3±0.02	15.3±0.18a*$
MCHC (g/dl)	34±0.5	33.5±0.15	33.9±0.1	32.5±0.26a*$
RDW SD (fl)	34.6±0.2	35.8±0.05a	33.1±0.05b*	35.1±0.1**$
RDW CV (%)	17.2±0.20	17.2±0.15	16.2±0.15a	17.6±0.11c*$

 

Among the Control, NaAsO2, NaAsO2+Na2SeO3, and Na2SeO3 exposed group of mouse hematological parameters are evaluated and compared. Values are presented as mean ± SEM (n=3). TC: total count; WBC: White blood cell; Hb: Hemoglobin; TCE: Trichloroethylene; RBC: Red blood cell; PCV: Packed cell volume; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; RDW-SD: red blood cell dimension width-standard deviation; RDW-CV: Red cell distribution width-coefficient of variation. a, b, and c indicate a significant difference from the control. *, ** indicates the significant (p=<0.05) difference from NaAsO2. $ indicates the significant difference (p=<0.05) from (NaAsO2+Na2SeO3).

 

Table 2: Biochemical Parameters of different treatment groups of mice.

Parameters	Treatments
	Control	NaAsO2	NaAsO2+Na2SeO3	Na2SeO3
RBS (mmol/L)	3.2±0.05	5.4±0.11a	3.1±0.05*	4.3±0.05b**$
ALT (SGPT) (U/L)	12±0.57	17±0.57a	8±0.28b*	14±0.57c$
Alkaline phosphatage (U/L)	109±0.57	192±2.30a	128±4.72b*	97±1.52c**$
Total Cholesterol (mg/dl)	134±0.57	274±2a	174±3.05b*	196±2.08c**$
Triglyceride (mg/dl)	209±2.08	285±2.88a	252±1.52b*	244±3.05c**
Uric acid (mg/dl)	1.6±0.05	3.7±0.05a	2±0.05b*	2.1±0.05c**

 

Serum biochemical assessment and comparison among control and NaAsO2, NaAsO2+Na2SeO3, and Na2SeO3 exposed adult female mice. Data are presented as mean ± SEM (n=3). RBS: Random blood sugar; ALT: Alanine transaminase; SGPT: Serum glutamic pyruvic transaminase. a, b, c indicates the significant difference from the control. *, ** indicates the statistically significant (p<0.01, respectively) difference from NaAsO2. $ indicates the statistically significant (p<0.01, respectively) difference from (NaAsO2+Na2SeO3). Serum RBS, ALT (SGPT), Alkaline phosphatase, Total cholesterol, Triglyceride and Uric acid levels in the Na-arsenite group were 5.4±0.11, 17±0.57, 192±2.3, 274±2, 285±2.88 and 3.7±0.05 respectively which are significantly (P<0.01, respectively) higher than that of the control group measuring at 3.2±0.05, 12±0.57, 109±0.57, 134±0.57, 209±2.08 and 1.6±0.05 respectively (Table 2). With the ameliorative effect of the selenium, however, the Na-arsenite+Na-selenite group registered a significant (p<0.01, respectively) reduction of biochemical parameters than the Na-arsenite treated group.

 

Table 3: The organ-to-body weight ratio of different treatments groups.

Treatments	Organ to body weight
	Liver	Lung	Kidney	Heart	Spleen	Uterus
Control	6.95±0.59	1.37±2.85	1.73±0.39	0.45±0.06	0.59±0.05	0.98±0.39
NaAsO2	6.02±0.42	0.84±0.09	1.06±0.10	0.37±0.00	0.35±0.04*	0.37±0.06
NaAsO2+Na2SeO3	6.11±0.41	1.11±0.05	1.29±0.16	0.47±0.07	0.37±0.06**	0.68±0.14
Na2SeO3	6.11±0.76	1.03±0.09	1.59±0.23	0.46±0.04	0.57±0.11	0.88±0.24

 

The organ-to-body weight ratio was assessed and compared among the control, NaAsO2, NaAsO2+Na2SeO3, and Na2SeO3 exposed adult female mice. Values are presented as mean ± SEM (n=3). *Indicates statistical significance (p<0.02) between control and sodium arsenite exposed group. **Indicates statistical significance(p<0.05) between control and NaAsO2+Na2SeO3 exposed group of mice.

 

liver dysfunction as well as with other organ problems. The results showed that the abnormalities in various biochemical parameters posed by the Na-arsenite treatment among the Swiss albino female mice were successfully ameliorated by the Na-selenite treatment as shown in the Na-arsenite+Na-selenite group (Table 2). Serum RBS, ALT (SGPT), Alkaline phosphatase, Total cholesterol, Triglyceride and Uric acid levels in the Na-arsenite group were 5.4±0.11, 17±0.57, 192±2.3, 274±2, 285±2.88 and 3.7±0.05 respectively which are significantly (P<0.01, respectively) higher than that of the control group measuring at 3.2±0.05, 12±0.57, 109±0.57, 134±0.57, 209±2.08 and 1.6±0.05 respectively (Table 2). With the ameliorative effect of the selenium, however, the Na-arsenite+Na-selenite group registered a significant (p<0.01, respectively) reduction of biochemical parameters than the Na-arsenite treated group. In this group, Serum RBS, ALT (SGPT), Alkaline phosphatase, Total cholesterol, Triglyceride and Uric acid levels were 3.1±0.05, 8±0.28, 128±4.72, 174±3.05, 252±1.5, 2±0.05 respectively (Table 2).

Organ to body weight ratio assessment

We measured body weight and the ratio of organ-to-body weight to assess the rescue effect of selenium on arsenic-induced toxicity. The organ-to-body weight analysis of various vital organs like the liver, lungs, kidney, heart, spleen, and uterus revealed that only the spleen registered the ameliorative effect of the arsenic and selenium (combined) treatment group (Table 3). According to the results, spleen weight in the Na-arsenite exposed group was 0.35±0.04 significant (p<0.02) reduction from the control group which stands for 0.59±0.05 (Table 3). This detrimental effect of Na-arsenite exposure was significantly (p<0.05) higher by the Na-selenite treatment as shown in the Na-arsenite+Na-selenite group with a value of 0.37±0.06 (Table 3).

The rescue effect of selenium on arsenic-induced toxicity of organ morphology

The impact of Na-arsenite on different organs was assessed in adult female mice, and their amelioration with the supplementation of sodium selenite (Figure 1) was compared among different treatment groups. Visual observation of the morphological characteristics of different organs showed slight discoloration and abnormal consistency of the liver (Figure 1A, B) and lung (Figure 1B, E, F), which were substantially affected in the NaAsO2-exposed group compared to a non-treated control group. Interestingly, the liver (Figure 1C) and the lung (Figure 1G) in the NaAsO2+Na2SeO3-treated group comparatively improved compared to the sodium arsenite-exposed group.

 

Arsenic and selenium are comparable to one another in terms of their chemical composition and metabolic fates (Zeng et al., 2005). To a certain extent of exposure, both also exhibit cytotoxicity and anticancer action; however, selenium exhibits lower levels of cytotoxicity, genotoxicity, and oxidative toxicity than arsenic. Combination therapy is gaining popularity in the medical community recently for the treatment of diseases like cancer, neurological disorders, and others to ensure beneficial effects on the target objects (Hsueh et al., 2017; Wang et al., 2015). Selenium is regarded as a key regulator of this protein’s production and function, which strengthens cellular defenses both in vivo and in vitro (Schnabel et al., 2008). From this vantage point, we conducted this study to determine the protective effects of selenium on arsenic-induced hematological, biochemical, and defective organ development in adult female mice. The analysis of hematological and serum biochemical parameters yields crucial knowledge about the changes that take place in the physiology of the blood in the presence of sickness or hazardous pollution (Ola-Davies and Akinrinde, 2016). The study demonstrated a significant increase in total WBC count and platelet count in arsenic-exposed groups due to leukocytosis and thrombocytosis (Ola-Davies and Akinrinde, 2016). The impact was noticeably reversed when the mice were supplied with a Na-selenite and Na-arsenite combination, which significantly reduced the parameters. The results also showed that RBC count, Hb, and PCV significantly increased in the arsenic-treated group, which is comparable with the study of an increase or reduction in the number of red blood cells that can be caused by arsenic depending on the quantity and method of delivery, according to prior research (Yi et al., 2020). Hypoxia, or low oxygen partial pressure, causes the release of erythropoietin (EPO), which increases the formation of red blood cells (Wojan et al., 2021). The present study demonstrated that the co-supplementation of Na-selenite with arsenic rescued the hepatotoxicity by a significant reduction of the parameters. As an important antioxidant, selenium affects a variety of tissues and cells by increasing the amount of selenoproteins such GPx. Its principal role is to protect against oxidative damage by removing reactive oxygen species (ROS), especially hydroperoxides (Zhang et al., 2023). The liver is one of the most crucial and active organs for the retention, distribution, and detoxification of toxins (Akan et al., 2012) and to assess the liver, there are several tests available. Typically, the levels of ALT and ALP are evaluated to detect problems with the bones, gallbladder, kidney, and liver cells. ALP is found in a range of tissues, including the liver, bones, intestines, kidneys, and other organs, whereas ALT is believed to be largely concentrated inside liver cells. Most cases of liver damage or inflammation result in some elevation in ALP and ALT values (Barai et al., 2017). On the other hand, one of the major issues in cases of arsenic poisoning is oxidative damage. One of the most crucial methods to stop harm to this hazardous metal is to increase the antioxidant potential of arsenic pollutants. In the current study, we demonstrated that mice exposed to arsenic compared to control animals had considerably higher serum levels of ALP and ALT. According to prior research, elevated levels of these enzymes suggested liver damage in exposed animals (Barai et al., 2017; Mazumder, 2005; Zhang et al., 2014). However, ALT and ALP levels were lower in the animals exposed to both arsenic and sodium selenite supplementation than they were in the arsenic-alone exposure group, demonstrating that selenium has a significant ameliorative impact on the toxicity caused by arsenic. Previous studies demonstrated that selenium possesses a protective role against arsenic-induced hepatic damage by reducing lipid peroxidation and restoring glutathione peroxidase (GPx) activity in the liver (Xu et al., 2013). Due to perfusion and a rise in expelled chemical concentration in renal tubular cells, the kidney is more susceptible to injury (Messarah et al., 2013). Renal function is determined by urea levels in the serum. Only after parenchyma tissue damage does the urea levels start to rise (Messarah et al., 2013). In this study serum urea level was significantly higher in the arsenic-exposed group compared to the control which is comparable with the earlier studies (Messarah et al., 2013; Raeeszadeh et al., 2022; Singh et al., 2015). But interestingly the remarkable restoration of blood urea level after selenium treatment with arsenic showed that the kidney was protected against arsenic poisoning. Selenite treatment has been demonstrated to reduce arsenite’s harmful effects on antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) and to decrease renal lipid peroxidation. Furthermore, selenite therapy shields renal tissue against the histopathological alterations caused by arsenite (Jalaludeen et al., 2015). As per the literature, this hyperlipidemic condition imposed by arsenic is an outcome of oxidative stress (Sinha et al., 2010). The antioxidant properties of selenium effectively protect such oxidative imbalance evidenced by the observed values of lipid profile. In this study, we also found that serum RBS, total cholesterol and triglyceride levels were significantly higher in an arsenic-treated group than the control which is similar to the previous studies (Raeeszadeh et al., 2022; Yousef et al., 2008). The pancreatic islet cells are damaged by increased oxidative stress brought on by arsenic exposure, which raises blood glucose levels and disrupts lipid metabolism. Decreased fatty acid oxidation inside the mitochondria may be the result of increased oxidative stress brought on by mitochondrial damage within the hepatocytes However, supplementing with selenium and arsenic significantly decreased levels of RBS, total cholesterol, and triglycerides. The outcomes of the present work showed that supplementation of sodium selenite alone surprisingly had a toxic effect. Because of its enduring potential for adverse effects, arsenic buildup in cells and tissues is a serious issue. When consumed by humans or animals, arsenic is known to accumulate in several organs, including the liver, kidneys, heart, lungs, muscles, and spleen (Barai et al., 2017; Dua et al., 2015; Sayed et al., 2015). In this study, Na-arsenite-exposed mice showed a substantial decrease in spleen weight compared to the control group. Our results are in line with other studies that showed that increasing MDA and H2O2 levels cause the spleen to generate an oxidative imbalance that severely disrupts the function of the antioxidant enzymes CAT and GSH-Px, confirming oxidative damage to immunological organs (Duan et al., 2017). But the antioxidant properties of selenium with the supplementation of arsenic were able to significantly reduction of organ damage by improving the spleen weight (Table 3) and organ morphology (Figure 1) whereas sodium selenite alone was firmly contradictory. Throughout many life science fields, histopathology is a fundamental subject that provides a primary method for examining the microscopic features of tissues and making a wide range of illness diagnoses. However, in the context of this study, histopathological analysis of various organs poses a significant limitation in determining organ-specific alterations.

Conclusions And Recommendations

The current study has demonstrated the mitigating effect of Na2SeO3 on hematological and serum biochemical parameters and the development of internal organs altered by sodium arsenite exposure in adult female mice. Oxidative stress has been identified as one of the main processes of arsenic toxicity. By this concept, sodium selenite’s capacity to reduce oxidative stress may protect against the toxicity caused by arsenic. Numerous selenoproteins with antioxidant and detoxifying capabilities may have aided overall safety from the negative consequences. Sodium selenite has tremendous potential to reduce the negative effects of arsenic. These outcomes could potentially emphasize the role of selenium in reducing arsenic-induced toxicity in both people and animals. although its precise function in this process is yet unclear. Further experimentation is needed to clarify the effect of selenium against arsenic toxicity at the molecular level of observations and formulate an amelioration strategy. Therefore, it’s critical to conduct additional research on the physiological, cellular, and molecular mechanisms of selenium against arsenic-induced toxicity. Such research initiatives may lead to the creation of a therapeutic drug based on selenium that is intended to lessen the negative consequences that result from human exposure to arsenic.These outcomes could potentially emphasize the role of selenium in reducing arsenic-induced toxicity in both people and animals, although its precise function in this process is yet unclear.

ACKNOWLEDGMENTS

The authors are grateful to the staff of the Laboratory Animal Facilities of the Advanced Animal Research Farm, Department of Genetics and Animal Breeding, Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh to carry out this study. The authors greatly acknowledge the support of the Institute of Research and Training (IRT), Hajee Mohammad Danesh Science and Technology University, Dinajpur-5200, Bangladesh

Novelty Statement

The novelty of this study is that it provides preliminary information on the ameliorative effects of selenium against arsenic-induced hematological and biochemical alteration and organ development anomalies in female mice and these findings may lead to the creation of a therapeutic drug based on selenium that is intended to lessen the negative consequences that result from human exposure to arsenic.

Author’s Contribution

Conceptualization and design of the research, M.R.I.; methodology, M.R.I.; experimental investigation, M.K.B., S.S., M.S.H., and S.S.; sample resources, M.R.I.; writing-original draft preparation M.K.B., S.S., and M.R.I.; writing-review and editing, M.K.B., S.S., M.S.H., S.S., and M.R.I; supervision, M.R.I.; project administration, M.R.I. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by grants (ES-381) Under Special Allocation for Science and Technology from the Ministry of Science and Technology (MOST), Government of the People’s Republic of Bangladesh.

Compliance with ethical standards

This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors have declared no conflict of interest.

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