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Full Research Article

Therapeutic Effect of Essential Oils (Citrus sinensis) against Ehrlich Ascites Model Induced Renal Toxicity in Female Mice

Haneen Mushtaq Hameed1, Zainab Haytham Razooki2, Ahmed Flayyih Hasan1,*, Ali Abdul Azeez Abdul Rasool3, Ibrahim Jabber Abed4
1Biotechnology Research Center, Al-Nahrain University, Baghdad, Iraq.
2Department of Plant Biotechnology, College of Biotechnology, Al-Nahrain University, Baghdad, Iraq.
3Department of Biology, Al-Farabi University College, Baghdad, Iraq.
4Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq.

ABSTRACT

Background: Cancer is one of the most dangerous diseases of the twentieth century and the speed of its spread is horrific. It is characterized by cellular growth and invades all tissues of the body. In recent years, all countries of the world have turned to cancer research in order to identify new drugs to treat cancer from various sources , Cancer is the most common disease that causes death in the world and this is attributed to many pathological factors, such as reactive  oxygen species, which contribute to the initiation, spread and development of cancer.

Methods: Our current research aims to investigate the therapeutic role of essential oils (C.S.) against Ehrlich Tumor renal damage in Mice. The mice were divided into four group (Gp1, control group, Gp2, Essential oils (C.S) group, Gp3, EAC group, Gp4, EAC with Essential oils (C.S).

Result: Results showed the Essential oils (C.S) in pretreated (G4) lead to an improvement in  urea, creatinine levels  when compared to the EAC group. Through our results, it was shown that treatment with essential oils (C.S.) improved the levels of urea and creatinine comparing to the Gp3. It was noted that treatment with essential oils (C.S.) improved kidney tissue and VEGF protein expression the Gp4 compared to the Gp3 Groups. It could be concluded that essential oils (C.S) has a possible benefit to the kidneys against EAC induce kidney Toxicity.

INTRODUCTION

Cancer is one of the most dangerous diseases of the twentieth century and the speed of its spread is horrific. It is characterized by cellular growth and invades all tissues of the body (Kaufman et al., 1996). In recent years, all countries of the world have turned to cancer research in order to identify new drugs to treat cancer from various sources (Sannigrahi et al., 2012; Hasan et al., 2024). Cancer is the most common disease that causes death in the world and this is attributed to many pathological factors, such as reactive - oxygen species (ROS) , which contribute to the initiation, spread and development of cancer, Oxidative stress can cause genetic instability and be a cause of the development of cancer, Also, (ROS) is considered responsible for Transcription factors and disease induction (Adriana et al., 2006; Al-Dulimia et al., 2022; Hasan et al., 2024). The spread of the tumor inside the cells causes immunosuppression and inhibition of all the body’s anti-tumor functions due to the weakness of the immune system (Singh et al., 2005). There are many methods of preventing or treating cancer, the most common of which is chemotherapy, which is considered more effective, but it is very important to conduct many researches in the field of cancer for the purpose of treating those affected without harming the patient’s normal cells (Dash et al., 2007; Sharma et al., 2022; Naik et al., 2021). Ehrlich’s ascites carcinoma (EAC) is a malignant tumor, but it is undifferentiated, has a short lifespan, has the ability to metastasize, does not have a tumor-specific culture antigen and is very dangerous (Hasan et al., 2024). Essential oils are plant extracts used as aromatherapy and are considered alternative medicine and have the ability to relieve pain (Manzur et al., 2023). Essential oils are originally a group of compounds extracted from fruits and seeds for the purpose of obtaining oil in several different concentrations. They directly target the olfactory receptors, affecting the central nervous system. These oils contain anti-bacterial, anti-cancer and anti-fungal activity (de Aquino et al., 2023; Rajkumar et al., 2023). Essential oils (orange peels) are concentrated and effective oils that have many benefits, including improving sleep quality, reducing depression and reducing anxiety. These oils contain a substance called (Limonene) as a natural substance that prevents the growth of cancer cells and kills them in many cases of colon, prostate and lung cancer (Amala Dev et al., 2023; Hamdi et al., 2023; Hamdan et al., 2024). Orange oils are rich in vitamin C, thymine and many antioxidants and have health benefits. Orange oil contains many chemical agents that stimulate blood circulation and preserve the skin, such as myrcene, limonene, camphor and eugenol (Brito et al., 2021; Li et al., 2021).

MATERIAL AND METHODS

Essential oils (Citrus sinensis)
 
These oils were extracted from (Citrus sinensis) by evaporation method (Cleavenger) as per the method described by (Khalaf et al., 2021).
Animals
 
40 mice (female albino Swiss) were purchased. Their weight ranged between (20-25 grams) and their age ranged from 11 to 12 weeks. They were warmed at a temperature of 25°C and placed in special cages according to method of Mutar et al., (2020). The present study was carried out In the Department of Plant Biotechnology, Biotechnology Research Center, Al-Nahrain University, Baghdad, Iraq.
 
Induction of ehrlich ascites model celle
 
EAC cells were purchased from the Egyptian National Cancer Institute and these cells were placed in an equal saline solution, after which each mouse was injected with these cells intraperitoneally (ip) at a dose of (2.5 × 106 cells/20 g body weight). The use of the animal for the experiment was approved by the Institutional Animal Care and Use Committee approval number - IACUC-SCI-TU-0233. All the mice were monitored on a daily basis until the tumor appeared on the eighth, ninth, tenth and Fourteenth days.
 
Experimental design
 
The mice were divide into four groups of (10 mice each/group).
1st group: Natural mice.
2nd group: Mice treated with essential oils (Citrus sinensis) at an oral dose (25 mg/Kg. body weight/day) according to (Parmar et al., 2008).
3rd group: Mice treated with EAC cell line intraperitoneally according to (Hasan et al., 2023).
4th group: Mice treated with EAC cells and treated with essential oils (Citrus sinensis) for fourteen days in a row. This study began in July 2020 and the practical part was completed in April 2022.
 
Blood and tissue sample collection
 
Following the conclusion of the trial, the mice were put in a cage containing the sedative sodium pentobarbital (³100 mg/kg) for the purpose of anesthetizing the mice and dissecting them. Blood was drawn from the inferior vena cava into tubes containing heparin and the plasma was separated by a centrifugation at 3000 g for 20 minutes and stored in tubes. at -20°C. Kidney tissue was also collected and placed in a saline solution containing 10% diluted formalin, to perform histological examination and immunohistochemistry.
 
Biochemical assays
 
Serum urea and creatinine concentration tests were conducted by Diamond Company in Egypt according to (Ezz et al., 2023; Hasan et al., 2022). Rewrite this sentence as “Serum urea and creatinine were estimated using diagnostic kits obtained from (Kandeler et al., 2024), following the methods of Eisenhofer et al., (2023).
 
 Immunohistochemical investigation
 
Kidney tissue was extracted after cutting from all groups and fixed with 10% formalin for a period between (24-48 hours) and the tissue sections were stained with eosin and hematoxylin (E and H) for histological examination according to method of Alankooshi et al., (2023); Hasan et al., (2024).
 
Histopathological examination
 
The kidney tissues were fixed with 10% formalin for 48 hours. Kidney sections were fixed and dried in a layer of paraffin and stained with Hematoxylin and Eosin according to method of Hameed et al., (2023) and Hasan et al., (2021).
 
Statistical analysis
 
The Statistical Package for the Social Sciences (SPSS software version 16) was used to analyze the findings. The data were displayed as mean ± standard error of mean (SEM) and subjected to one-way analysis of variance (ANOVA) and Dunnett test statistical analysis. Comparisons using the Dunnett test were used to determine how significant the differences between the groups were. To compare the significant difference between groups, an unpaired T-test was used. P<0 05 was established as the threshold for statistical significance.

RESULTS AND DISCUSSION

Recently, scientists have become widely interested in the field of discovering new treatments for cancer and essential oils (Citrus sinensis) have been of interest due to their broad effectiveness as an antioxidant. The main benefit of our research is knowing the therapeutic role of essential oils (Citrus sinensis) as an antidote to kidney toxicity caused by EAC. Our results indicate that EAC initiates changes in kidney function as detected by elevations in urea levels and depletion of creatinine levels. The results showed that EAC cells cause changes in kidney function in the EAC group (Fig 1 and 2), as they cause an increase in urea levels compared to the control group. These results were supported by the findings of Aldubayan et al., (2019) and a decrease in creatinine levels in the EAC group compared to the control group. These results differ from the findings of Mutar et al., (2020). Our results indicate that EAC causes damage to kidney tissue compared to the essential oil group and these results were supported by the findings of Hasan et al., (2023). Our current results showed that treatment with essential oils (Citrus sinensis) treats kidney functions, as we notice a decrease in urea levels and an increase in creatine levels. Our results agreed with findings of Mohamed et al., (2010) and Alharbi et al., (2023). Also, our results showed an improvement in kidney tissue in the fourth group (Citrus sinensis) compared to the EAC group (Fig 3). These results were supported by (the findings of Soji-Omoniwa et al., (2014) and Bouzenna et al., (2016). Vascular endothelial growth factor (VEGF), was initially identified as a mitogen unique to endothelial cells, VEGF is generated by a variety of cell types, including as renal mesangial cells, keratinocytes, macrophages, platelets and tumor cells.
 

Fig 1: A set of figures showing the growth of EAC cells from the first day to the fourteenth day according to (Hameed et al., 2024).


 

Fig 2: Effect of essential oils (C.S) on renal function parameters in the serum of EAC bearing mice.


 

Fig 3: Essential oils (C.S) improved renal tissue against EAC induced histopathological changes photomicrographs of kidney sections in the different experimental groups stained with haematoxylin and eosin.


       
In the immunochemical examination of VEGF proteins, our results showed a positive reaction in renal tubules and glomeruli in kidney tissue for EAC cells in the third group compared to the control group according to Deluque et al., (2022) and Elhady et al., (2022).
       
The method of treatment with essential oils (Citrus sinensis) for tumor-bearing mice in the fourth group showed an improvement and a decrease in VEGF protein in kidney tissue compared to the EAC group (Fig 4) due to its effects on the cells. Our results agreed with (Rojas-Armas et al., 2022; Miastkowska et al., 2021).
 

Fig 4: Effect of Essential oils (C.S) on Renal VEGF protein expression photomicrographs of kidney sections in the different experimental groups stained with Vascular endothelial growth factor (VEGF).

CONCLUSION

These results indicate that Essential oils (Citrus sinensis) may be an innovative and dependable therapy For EAC, confirm the malignant activity even more of  essential oils (Citrus sinensis) as a possibility Based on what we’ve found, it appears that Essential oils (Citrus sinensis)  can serve as a successful course of therapy  against EAC, We advise more testing and investigation into its efficacious application in the management of various ailments.

ACKNOWLEDGEMENT

This study did not receive any grant from any funding agency.
 
Data availability
 
Data supporting our study results are accessible from the relevant author whenever needed.
 
Funding
 
No financial support for our research.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

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