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BY 4.0 license Open Access Published by De Gruyter Open Access May 5, 2023

The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study

  • Khalid M. Al Syaad , Amin A. Al-Doaiss , Ahmed Ezzat Ahmed , Haitham El-Mekkawy , Mohamed Abdelrahman , Ahmed A. El-Mansi , Muhammad Fakhar-e-Alam Kulyar and Montaser Elsayed Ali EMAIL logo
From the journal Open Chemistry

Abstract

The present study investigated the toxic action of acrylamide (ACR) and the abrogative effect of aqueous propolis extract on ACR-induced toxicity in male albino rats. Forty adult male albino rats were randomly divided into four groups and administered the treatment doses orally by gavage. Control, treated with a physiological solution (5.0 ml/rat). ACR-treated group, treated with ACR 25 mg/kg. ACR + propolis, treated with 25 mg/kg ACR + 100 mg/kg propolis. Propolis-treated group, treated with 100 mg/kg. The treatment period was 28 days, the treatment doses were administered orally using a gavage stomach tube. The results showed that the presence of ACR increased (P < 0.001) the level of liver enzymes alanine aminotransferase (167.2 vs 90.15) and aspartate aminotransferase (120.66 vs 41.52) in the liver tissue serum and lipid peroxidation products (80.11 vs 39.3); also, it decreased (P < 0.001) the total capacity of antioxidants (113.4 vs 189.41) compared to the control group. The histological analysis of the kidney revealed alterations induced by ACR, including atrophy, necrosis, renal glomeruli atrophy, tubular necrosis, enlargement of the glomeruli, hemorrhage, and edema surrounding the blood vessels. Also, the results showed that the rats treated with propolis improved liver and kidney functions because of propolis’s efficiency against the harmful effects of ACR. Moreover, the histological examination of the liver tissue revealed negative changes, with focal necrosis in hepatocytes. Microscopic examination showed tubular necrosis within the seminiferous tubules, sloughing, and desquamation of sperm cells into the lumen. Also, an infiltration of protein substances between the tubules and degenerative vacuolar changes between sperm cells was observed. The renal, hepatic, and testicular tissues appeared almost similar to the control group, except for some minor changes. This study proved that feeding the rats with propolis reduced these pathological effects and restored the tissues to a normal state. It is concluded that using propolis with ACR significantly reduced the biochemical and histological damage caused by ACR, and recommends using propolis as a cytoprotective agent against pathological toxicity of ACR.

1 Introduction

There has been widespread use of acrylamide (ACR) in many industries, such as cosmetics, paper, textile, wastewater treatment, printing materials, polymers, and copolymer production worldwide [1]; even in medicine, it has been used to create high molecular polymers like poly-ACR [2]. Acrylamide (C3H5NO) is a highly reactive, white, odorless crystalline toxic carbonyl compound with high-water solubility and chemical activities. Furthermore, there are numerous inadvertent ACR sources in daily life, such as processed foods, where ACR is created by the Maillard reaction between monosaccharaides and proteins while cooking these foods at high temperatures (>120°C). ACR is formed during the cooking of carbohydrate-rich foods such as potato chip fries, bread, biscuits, cereals, toasted bread, roasted coffee beans, crisps, malt beverages, fish, and chicken nuggets [3,4]. The International Agency for Research on Cancer classified ACR as a class 2A drug in 1994 because it was most likely carcinogenic to humans [2]. Many studies have indicated that ACR has a toxic effect that disturbs different body organs and systems (hepato-nephrotoxicity, neurotoxic, genotoxic, and carcinogenic effects and has a reproductive toxic action) [5,6,7]. In comparison, other studies showed that ACR has neurotoxic and hepatotoxic effects, as well as pathological embryogenesis [6,8,9]. ACR is absorbed in the alimentary tract and metabolized in the liver [10].

Globally, natural medicinal products have been increasingly used more than synthetic ones. In this regard, antioxidant-rich substances have been identified as potential therapeutic agents. Furthermore, because of their antioxidant activities, natural herbal products protect against toxic side effects and are used as chemotherapeutic agents [1,7]. Propolis is the natural resinous material of different plants and is collected by honeybees; it consists of many natural compounds [11]. Honeybees synthesize propolis, a sticky, resinous substance used in constructing and maintaining their hives, combining the waxes produced by them with resins gathered from various plants. Polyphenols (flavonoid aglycones, phenolic acids and their esters, phenolic aldehydes), alcohols and ketones, sesquiterpenes, quinones, coumarins, steroids, amino acids, and inorganic chemicals are all found in propolis [12,13]. It contains around 150 polyphenol components, including flavonoids, phenolic acid, and their esters [14]. Previously, different countries have used propolis for a long time to compact many diseases due to its antioxidant content [15]; therefore, it is commonly used in traditional medicines. Also, many previous recommendations exist for supplementing propolis in fighting diseases and cancer prevention [16,17]. In addition, investigators are interested in propolis potential to minimize the adverse effects of cancer therapy [18,19]. Caffeic acid phenethyl ester (CAPE), an active ingredient of propolis, could depress tumor growth by signaling networks that control the growth of the cancer cells in breast, bladder, and prostate cancers [20].

Moreover, propolis flavonoids showed cytotoxic activity against fibrosarcoma and lung adenocarcinoma [16]. In addition, some studies reported that propolis has anticarcinogenic properties through immunomodulation action [21]. The extracts of propolis have been attributed to biological and pharmacological activities, such as free radical scavenging, antitumor, local, immunomodulatory effects, anesthetic, anti-inflammatory, antibiotic, antioxidative, antiviral, antimicrobial, antifungal [13,14]. Free radical scavenging is one of the propolis therapeutical actions; according to many in vivo and in vitro studies, it is used as a stimulant agent of the immune system [22]. Moreover, this natural product was reported to support tissue regeneration and blood capillary strengthening [23]. However, the studies evaluating propolis’s efficiency against ACR toxicity are still limited.

The current study aims to evaluate the histological and histochemical changes in the hepatic, renal, and testicular tissues induced by oral administration of ACR and the potential protective role of the propolis extract against ACR-induced toxicity in rats.

2 Materials and methods

All experiments were carried out in the Physiology Lab., Department of Biology, College of Science, King Khalid University, Saudi Arabia.

2.1 Chemicals

Acrylamide (catalog No: A9099; Sigma-Aldrich, St. Louis, MO, USA) and propolis (catalog Sigma-Aldrich, St. Louis, MO, USA) were used in this study.

2.2 Experimental animals

Forty adult male Wistar albino rats (10–12 weeks old) weighing 200–230  g were used in this study. Animals were randomly divided into four groups (n = 10 per group). Control, treated with a physiological solution (5.0 ml/rat). ACR-treated group, treated with ACK 25 mg/kg. ACR + propolis, treated with 25 mg/kg ACR + 100 mg/kg propolis. Propolis-treated group, treated with 100 mg/kg. Animals were housed under standard temperature conditions (23 ± 2°C) and lighting (12 h; light/dark cycles), with free access to food and drinking water ad libitum. The experiment lasted for 28 days, and the treatment doses were administered orally by gavage.

2.3 Collection of serum and estimation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total antioxidant capacity (TAC), thiobarbituric acid reactive substance (TBARS)

At the end of the experimental period, blood samples were taken from the retro-orbital plexus under light ether anesthesia without anticoagulant and allowed to clot for 10 min at room temperature. The blood was centrifuged at 3,500 rpm for 10 min at 0°C to obtain the serum. The serum collected was kept at ‒80°C until used. The enzymes for liver functions included AST, estimated according to Belfield and Goldberg [24], and ALT, estimated according to Kind and King [25]. Also, the TAC (Biodiagnostic) was measured according to Koracevic et al. [26]. In contrast, lipid peroxidation and TBARS were measured according to Svingen et al. [27], and determined in the homogenized liver samples of all groups. Biochemical analysis was performed using Spectrophotometer Model 25 Lambda (manufactured by Elmer Perkin, Germany).

2.4 Histology

Fresh samples of each rat’s liver, kidney, and testes were rapidly dissected and fixed in neutral buffered formalin (10%). The fixed specimens were processed according to El-Refaiy and Eissa [28] for dehydration with different grades of ethanol (70, 80, 90, 95, and 100%), clearing in two changes of xylene and impregnation with two changes of molten paraffin wax, using an automatic tissue processor (Sakura, Japan). The specimens were embedded and blocked using an embedding station (Sakura, Japan). Serial sections of 4–5 µm thickness were cut using a microtome (ModelRM2245; Leica, Germany), while an autostainer (Model 5020; Leica, Germany) was used for hematoxylin/eosin staining of the sections. Histochemical staining was performed using standard hematoxylin eosin and periodic acid schiff techniques [29]. The mounted specimens were examined for alterations in the hepatic tissues of each rat under study using an optical microscope (Olympus Microscope with Digital Camera DP73, Japan). An experienced pathologist performed all subsequent histopathological examinations without knowledge of the previous treatments. Stained sections of control and treated rats were examined for alterations in the architecture.

2.5 Statistical analysis

The biochemical parameters were represented as mean ± standard deviation (SD). Differences between mean values in different groups were tested for significance using a one-way analysis of variance followed by Duncan’s test, and P < 0.05 was considered significant using the statistical analysis system (SPSS, 1996).

3 Results

3.1 Biochemical parameters

The animals treated with ACR exhibited a significant increase in the liver profile enzymes (P < 0.05) in ALT, AST, TAC levels, as well as lipid peroxidation (TBARS) compared to the control group and treated groups (Table 1). Meanwhile, propolis enhanced liver and kidney functions in rats treated with ACR and propolis. In contrast, a significant decrease was observed in ALT and AST enzymes compared to samples treated with ACR only (Table 1).

Table 1

AST, ALT levels, and TAC in the serum and the level of lipid peroxidation (TBARS) in the liver tissue

Parameters mean ± SD Control Acrylamide Acrylamide + propolis Propolis
TBARS (nmol/g tissue) 39.3 ± 3.51 80.11 ± 4.43*** 48.7 ± 4.23 38.66 ± 4.22
TAC (µm/l) 189.41 ± 8.1 113.4 ± 7.2** 170.23 ± 6.9 194.2 ± 7.11
ALT (mg/dl) 90.15 ± 7.61 167.2 ± 8.17*** 122.04 ± 7.47* 87.07 ± 6.1
AST (mg/dl) 41.52 ± 4.51 120.66 ± 7.4*** 77.4 ± 6.41* 48.13 ± 5.01

Mean ± SD, ***P < 0.001, **P < 0.01, *P < 0.05, significant compared with the control group.

There was a significant increase (P < 0.001) in the level of lipid peroxidation products (TBARS) in the liver tissues of the ACR-treated group compared with the control group. In contrast, a non-significant increase (P > 0.05) was observed in the ACR + propolis-treated group and a non-significant decrease in the propolis-treated group compared to the control group (Table 1).

The study showed a significant decrease (P < 0.01) in the TAC level in the serum of the ACR-treated group. Moreover, there was a decrease (P > 0.05) in the ACR + propolis-treated group. Also, there was a non-significant increase in the propolis-treated group compared with the control group.

Meanwhile, the serum ALT and AST levels were higher (P < 0.001) in the ACR-treated group, and there was a significant decrease (P < 0.05) in the ACR + propolis-treated group compared with the control group. However, when treated with propolis, the liver functions improved and helped liver enzymes to return to normal levels (Table 1).

3.2 Histopathological studies

3.2.1 Renal alterations

The kidneys showed normal glomeruli and renal tubular microanatomy in the control group, as shown in Figure 1.

Figure 1 
                     Cross section of the kidney cortex of the control group, showing Bowman’s capsule (BC), proximal convoluted tubules (PCT), distal convoluted tubules (DCT), and normal blood vessels (arrows) between renal tubules.
Figure 1

Cross section of the kidney cortex of the control group, showing Bowman’s capsule (BC), proximal convoluted tubules (PCT), distal convoluted tubules (DCT), and normal blood vessels (arrows) between renal tubules.

Histopathological examinations of the kidneys of rats exposed to the ACR indicated the appearance of many histopathological changes, such as dilatation and congestion of glomerular capillaries, dilatation, and congestion of blood vessels between the renal tubules compared with the control rats.

In addition to the infiltration of protein materials inside and outside the renal tubules, hydropic degeneration in the cells of the renal tubules, atrophy in some renal glomeruli, necrosis, and edema or inflammatory edema, with some bleeding around renal blood vessels, infiltration of inflammatory cells and focal fibrosis in between the renal tubules were also seen (Figure 2a–h).

Figure 2 
                     (a–h) Photomicrographs of the cross sections of the kidney cortices in the ACR -treated group indicating dilated and congested glomerular capillaries (✺) and dilated and congested blood vessels between the renal tubules (✸). In addition to the infiltration of protein materials inside and outside the renal tubules (☼), hydropic degeneration in the cells of the renal tubules (H), atrophy in some renal glomeruli (△), necrosis (N), and edema or inflammatory edema (E), with some bleeding around renal blood vessels, infiltration of inflammatory cells (IF) and focal fibrosis (F) in between the renal tubules are also seen.
Figure 2

(a–h) Photomicrographs of the cross sections of the kidney cortices in the ACR -treated group indicating dilated and congested glomerular capillaries (✺) and dilated and congested blood vessels between the renal tubules (✸). In addition to the infiltration of protein materials inside and outside the renal tubules (☼), hydropic degeneration in the cells of the renal tubules (H), atrophy in some renal glomeruli (△), necrosis (N), and edema or inflammatory edema (E), with some bleeding around renal blood vessels, infiltration of inflammatory cells (IF) and focal fibrosis (F) in between the renal tubules are also seen.

The cortex of the kidney of the (ACR + propolis)-treated group and the propolis-treated group showed normal renal architecture with normal PCT, normal DCT, and normal peritubular blood vessels, and the absence of any pathological changes (Figure 3a and b).

Figure 3 
                     (a) A cross section of the cortex of the kidney of the (ACR + propolis)-treated group, (b) a cross section of the renal cortex of the propolis-treated group. The two sections show a normal renal architecture with normal glomeruli (G) surrounded by BC, normal PCT, DCT, and normal peritubular blood vessels (arrows) associated with the absence of any pathological changes.
Figure 3

(a) A cross section of the cortex of the kidney of the (ACR + propolis)-treated group, (b) a cross section of the renal cortex of the propolis-treated group. The two sections show a normal renal architecture with normal glomeruli (G) surrounded by BC, normal PCT, DCT, and normal peritubular blood vessels (arrows) associated with the absence of any pathological changes.

3.2.2 Hepatic alterations

Microscopic examination of the liver of control rats demonstrated a normal well-preserved architecture, with normal histological components of the hepatic lobules and portal areas, a normal central vein (CV) bounded by an intact endothelium. Parallel cords of hepatocytes radiate from the CV toward the periphery of the hepatic lobule and are separated by normal sinusoidal spaces in the liver of all control rats (Figure 4a and b).

Figure 4 
                     (a and b) Photomicrographs of a hepatic tissue cross section of the control group showing the CV, polygonal hepatocytes (H) with rounded nuclei (N); the hepatocytes are arranged in the form of hepatic cords radiating from the CV to the border hepatic lobule, separating the hepatic cords by small blood sinusoids (S).
Figure 4

(a and b) Photomicrographs of a hepatic tissue cross section of the control group showing the CV, polygonal hepatocytes (H) with rounded nuclei (N); the hepatocytes are arranged in the form of hepatic cords radiating from the CV to the border hepatic lobule, separating the hepatic cords by small blood sinusoids (S).

Histopathological examinations of the hepatic tissues of rats exposed to ACR indicated the presence of histopathological changes such as necrotic and hemorrhagic foci associated with pyknosis of the nuclei of hepatocytes compared to the control groups (Figure 5a and b).

Figure 5 
                     (a and b) A cross-section of hepatic tissue from the ACR-treated group showing necrotic (✺) and hemorrhagic (⇒) foci associated with pyknosis of the nuclei of hepatocytes.
Figure 5

(a and b) A cross-section of hepatic tissue from the ACR-treated group showing necrotic (✺) and hemorrhagic (⇒) foci associated with pyknosis of the nuclei of hepatocytes.

Hepatic tissue of rats of the ACR-propolis group and the propolis group showed normal hepatic architecture with normal CV, hepatocytes, and absence of any pathological changes (Figure 6a and b).

Figure 6 
                     Photomicrograph of (a) a cross-section of hepatic tissue from the (ACR + propolis)-treated group, (b) a cross-section of hepatic tissue from the propolis-treated group. The two sections show normal hepatic architecture with the normal CV, hepatocytes (H), and the absence of any pathological changes.
Figure 6

Photomicrograph of (a) a cross-section of hepatic tissue from the (ACR + propolis)-treated group, (b) a cross-section of hepatic tissue from the propolis-treated group. The two sections show normal hepatic architecture with the normal CV, hepatocytes (H), and the absence of any pathological changes.

3.2.3 Testicular alterations

Microscopic analysis of the testicular tissue from the control group revealed a normal testicular architecture with intact seminiferous tubules (ST) and normal interstitial tissue. The ST is lined with a stratified epithelium (SE) composed of spermatogenic cells, including spermatogonia, primary and secondary spermatocytes, spermatocytes, spermatids, and spermatozoa. The spermatogenic cells are associated with columnar supporting cells (Sertoli cells) and rest on a basement membrane (Figure 7a and b).

Figure 7 
                     (a and b) A cross section of testicular tissue from the control group showing the ST and interstitial tissue and interstitial cells (IC), the ST lined with an SE composed of spermatogenic cells: spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa in addition to columnar supporting cells (Sertoli cells). Note that the spermatogenic cells rest on a basement membrane (arrows).
Figure 7

(a and b) A cross section of testicular tissue from the control group showing the ST and interstitial tissue and interstitial cells (IC), the ST lined with an SE composed of spermatogenic cells: spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa in addition to columnar supporting cells (Sertoli cells). Note that the spermatogenic cells rest on a basement membrane (arrows).

The histological results showed several histopathological alterations in the ACR group compared to the control group. Edema, protein material infiltration between tubules, and degenerative vacuolar alterations were among the observed abnormalities. The seminal tubule tissue had degenerative alterations, sperm cell variations, sloughing off, and desquamation of spermatogenic cells, in addition to deformation and tortuosity of the basement membrane (Figure 8a and b).

Figure 8 
                     (a–d) A cross-section of the testicular tissue in the ACR-treated group showing edema and protein infiltration between the ST (☼) and sloughing off and desquamation of spermatogenic cells into the lumen of the ST (✺) with degenerative changes in the seminal tubule tissue (✸). Deformation and tortuosity of the basement membrane (arrows).
Figure 8

(a–d) A cross-section of the testicular tissue in the ACR-treated group showing edema and protein infiltration between the ST (☼) and sloughing off and desquamation of spermatogenic cells into the lumen of the ST (✺) with degenerative changes in the seminal tubule tissue (✸). Deformation and tortuosity of the basement membrane (arrows).

However, the propolis-treated group and the (ACR + propolis)-treated group exhibited healthy testicles. It showed healthy ST, interstitial tissue and cells, stratified epithelial tissue lining the ST made up of spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa, and some hydropic degenerations as well as normal basement membrane (Figure 9a and b).

Figure 9 
                     Photomicrographs of a testicular tissue cross section of male albino rat from (a and c) (ACR + propolis)-treated group, (b and d) the propolis-treated group. The two sections show normal testicular architecture with normal ST, normal interstitial tissue and IC, SE tissue lining the ST consisting of spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa with some hydropic degenerations (*) and good basement membrane (arrows).
Figure 9

Photomicrographs of a testicular tissue cross section of male albino rat from (a and c) (ACR + propolis)-treated group, (b and d) the propolis-treated group. The two sections show normal testicular architecture with normal ST, normal interstitial tissue and IC, SE tissue lining the ST consisting of spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa with some hydropic degenerations (*) and good basement membrane (arrows).

Although some minor changes remained in the (ACR + propolis)-treated group, the hepatic, renal, and testicular tissues were almost similar to the control group. The results of this study proved that supplementing propolis reduced the occurrence of these pathological effects and restored the tissues almost to a normal state.

4 Discussion

This experiment evaluated the effect of propolis orally by gavage, and the potential protective role in the rats’ hepatic, renal, and testicular tissues induced by propolis extract against ACR-induced toxicity.

The above results on the kidney section revealed that rats treated with ACR + propolis had a normal renal structure with PCT, and distal and blood vessels. This indicates that propolis positively reduced the harmful effects of ACR in kidney tissues. In contrast, there is an observed decrease in ALT and AST enzymes compared to samples treated with ACR only. Meanwhile, propolis prevented harmful effects on the main organ responsible for the biotransformation of various components and many toxic chemical substances [14,30]. The enzymes superoxide dismutase, catalase (CAT), and glutathione peroxidase (GSH-Px) activity convert superoxide radicals into hydrogen peroxide, and then water and molecular oxygen are the first lines of defense against oxidative stress. The redox state of the cells is altered when the activity of these enzymes is reduced. As a result, increasing the activity of these enzymes probably aids in the removal of ROS produced by pesticide exposure [13,31].

The current study revealed that ACR-treated affected hepatic alteration in rats; hydropic vacuolated degenerations in the cytoplasm and pycnotic nuclei were observed. Also, the CV and blood sinusoids were dilated and congested, and infiltration of inflammatory cells was also seen as a result of exposure to ACR. These ACR-induced alterations are consistent with the Rady and Osman’s [32] findings of hepatotoxicity following ingestion of an excess ACR-containing diet. In addition, the current research revealed congested CV and blood sinusoids could indicate metabolic abnormalities in the hepatic tissue, implying that ACR may have a toxic effect on the liver [33]. ACR may interact with cytochrome P450 to create glycidamide, resulting in glutathione depletion, an important antioxidant enzyme. As a result, oxidative damage interferes with cell function and may lead to cell death [33,34].

ACR-induced toxicity is driven by oxidative stress, oxygen generation, and apoptosis (Mehri et al., [35]). However, the cytoplasmic degeneration, necrosis, and metabolic enzyme activity defects are major ACR-hepatotoxic effects [36], in addition to the enlarged and congested CV and blood sinusoids, which were noticed by Hu et al. [37], Amin [33], and Hussein et al. [38].

In the present study, the testicular tissue of the rats treated with propolis showed healthy ST, interstitial tissue and cells, and SE tissue lining the ST made up of spermatogonia and primary and secondary spermatocytes. Most of the therapeutic properties of propolis are due to anti-inflammatory and antioxidant effects, which mitigate oxidative damage by scavenger-free radicals and are attributed to protecting normal histological structure in ACR + propolis-treated rats [13]. The beneficial properties of propolis have been linked to its high amount of flavonoids, phenolic acids, and terpenoids [14].

In the present study, the hepatic renal and testicular tissues of the (ACR + propolis)-treated group were almost similar to the control group, except that some minor changes remained. Propolis’ benefits may be due to its inhibitory effects on lipid peroxidation mechanisms, prevention of free radical formation, scavenging action on free radicals, and decreased levels of MDA [39]. CAPE is another active component of propolis, which is a practical component in reducing oxidative stress in the liver through reduced lipid peroxidation, as reported in several studies [14,16,30,40].

The biochemical parameters such as the total oxidative status and oxidative stress index were measured in hepatic tissue to examine if propolis might help reduce ACR-induced reno-hepatic and testicular damage. The results indicated an improvement in hepatic architecture in the (ACR + propolis)-treated group. Furthermore, the CVs and blood sinusoids are either normal or slightly dilated. Polygonal hepatocytes have vesicular nuclei and acidophilic cytoplasm in most cells. Some cytoplasmic degenerations are still present in some sections. In the present study, the increase in the presence of free radicals during oxidative stress caused damage to the membrane structure of hepatocytes, as indicated by the levels of AST, ALT, and TAC in serum and TBARS in tissues. These findings are consistent with ACR altering metabolic parameters in rats and causing DNA damage, inflammation, and oxidative stress in rat testes [38,41,42], besides the ACR’s negative effect on enzyme activity and lipid peroxidation [8,43].

5 Conclusions

Acrylamide has negative effects on animal and human health; however, propolis supplementation may reduce ACR’s adverse consequences and helps the liver, kidney, and testes return to their normal state. The effectiveness of propolis in reducing pathological changes caused by ACR may be due to the anti-inflammatory and antioxidant effects of propolis. Moreover, the blood biochemical findings in the present study confirmed the efficacy of propolis on ACR toxicity. Propolis can be used as a cytoprotective agent against ACR-induced toxicity. Further research is needed to determine the precise mechanism by which propolis protects against ACR toxicity.

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University, Abha, KSA, for funding this work through the research group project (G.R.P/23/43).

  1. Funding information: The deanship of scientific research, King Khalid University, Saudi Arabia, for the fund through the research group project (G.R.P/23/43).

  2. Author contributions: KMAS, AAA, and AEA: conceptualization, methodology, data curation, and writing the original draft. HEM, MA, and AAE: methodology, writing-review and editing, and critical reading. MEA and MFK: editing, critical reading, data curation, and formal analysis. All authors listed in this paper have contributed to the preparation and execution of this research. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

  4. Ethics statement: All experiments were reviewed and approved following the rules and regulations of the Research Ethics Committee, King Khalid University (Approval NO. ECM#2023-1206). All experiments were carried out in the Physiology Lab., Department of Biology, College of Science, and King Khalid University, Saudi Arabia. The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to.

  5. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-03-10
Revised: 2023-04-04
Accepted: 2023-04-05
Published Online: 2023-05-05

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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