Investigating the hepato-protective properties of chamomile oil and olive leaves extracts against ribociclib-induced hepatotoxicity

Investigando as propriedades hepatoprotetoras do óleo de camomila e extratos de folhas de oliveira contra a hepatotoxicidade induzida por ribociclibe

Abstract

A new approach to overcome or reduce these toxicities is by using antioxidants. Ribociclib, a CDK4/6 inhibitor used in the treatment of breast cancer, has been linked to hepatotoxicity and may contribute to the development of Hepatocellular carcinoma in rats. This Study aims to assess hepatoprotective effect of chamomile oil and olive leaf extracts against ribociclib-induced Hepatotoxicity in rats. A total of 40 adult male albino rats aged 9-10 weeks were utilized in this experiment. These rats were divided into four groups, (N=10). Group A (control) comprised normal rats administered 1 ml (10 ml/kg/day) of normal saline daily. Conversely, group B rats were administered 5 mg/kg Ribociclib (n = 10), while group C was administered 5 mg/kg Ribociclib with a 500 mg/kg/day dose of chamomile oil. Group D was given 5 mg \kg Ribociclib in combination with 200 mg/kg/day of olive leaves. After the trial, the animals were sacrificed, blood samples were collected for biochemical tests, and the liver tissue was processed for histological examination. The results of histology, and biochemistry parameter analysis, indicated that co-administration of Ribociclib and chamomile oil plays a decisive role in mitigating the hepatotoxicity result from Ribociclib-induced liver injuries in rats as demonstrated by histological and biochemical parameters.The levels of cholesterol and LDL in the blood were significantly lower (P < 0.01) after administering chamomile oil compared to the control group. The results of the current study demonstrated that the simultaneous use of chamomile oil and olive leaf extract significantly reduced the liver damage caused by Ribociclib and improved the lipid profile in Albino rats. Additionally, the use of chamomile extract notably lowered urea levels (p < 0.01), indicating a protective effect on the kidneys.

Keywords:
ribociclib; hepatotoxicity; hepatocellular carcinoma (HCC); olive leaves; chamomile oil; biochemical tests

Resumo

Uma nova abordagem para superar ou reduzir essas toxicidades é usar antioxidantes. O ribociclibe, um inibidor de CDK4/6 usado no tratamento do câncer de mama, tem sido associado à hepatotoxicidade e pode contribuir para o desenvolvimento de carcinoma hepatocelular em ratos. Este estudo tem como objetivo avaliar o efeito hepatoprotetor do óleo de camomila e extratos de folhas de oliveira contra a hepatotoxicidade induzida por ribociclibe em ratos. Um total de 40 ratos albinos machos adultos com idades entre 9 e 10 semanas foram utilizados neste experimento. Esses ratos foram divididos em quatro grupos (N = 10). O grupo A (controle) compreendeu ratos normais aos quais foi administrado 1 ml (10 ml/kg/dia) de solução salina normal diariamente. Por outro lado, os ratos do grupo B receberam 5 mg/kg de ribociclibe (n = 10), enquanto o grupo C recebeu 5 mg/kg de ribociclibe com uma dose de 500 mg/kg/dia de óleo de camomila. O grupo D recebeu 5 mg/kg de ribociclibe em combinação com 200 mg/kg/dia de folhas de oliveira. Após o teste, os animais foram sacrificados, amostras de sangue foram coletadas para testes bioquímicos e o tecido hepático foi processado para exame histológico. Os resultados da histologia e análise de parâmetros bioquímicos indicaram que a coadministração de ribociclibe e óleo de camomila desempenha um papel decisivo na mitigação do resultado de hepatotoxicidade de lesões hepáticas induzidas por ribociclibe em ratos, conforme demonstrado por parâmetros histológicos e bioquímicos. Os níveis de colesterol e LDL no sangue foram significativamente menores (P < 0,01) após a administração de óleo de camomila em comparação ao grupo controle. Os resultados do presente estudo demonstraram que o uso simultâneo de óleo de camomila e extrato de folha de oliveira reduziu significativamente os danos hepáticos causados ​​pelo ribociclibe e melhorou o perfil lipídico em ratos albinos. Além disso, o uso de extrato de camomila reduziu significativamente os níveis de ureia (p <0,01), indicando efeito protetor nos rins.

Palavras-chave:
ribociclibe; hepatotoxicidade; carcinoma hepatocelular (CHC); folhas de oliveira; óleo de camomila; testes bioquímicos

1. Introduction

An active organ, the liver controls the metabolism of fats and carbohydrates, among other physiological functions. Detoxifying potentially harmful substances, medicines, and environmental pollutants primarily depends on operating an appropriate and healthy live (Bechmann et al., 2012; Buabeid et al., 2022). The permeability of the cell membrane is changed by free radicals creating a covalent link with lipids, which results in tissue damage (Ayenew and Wasihun, 2023; Kumar and Deval Rao, 2008). Potential danger factors for the development of liver disease include pathogenic germs and viruses, hepatotoxins, drug overdose and duration, alcohol, obesity and malnutrition, autoimmune diseases, type-2 diabetes, and hereditary factors (Munir et al., 2022; Zhang et al., 2020). The most prevalent type of iatrogenic disease is hepatotoxicity, which is brought on by medication exposure (Singh et al., 2022). By compensating, liver cells can respond to reactive oxygen species (ROS) in many ways, some of which include the production of antioxidant proteins such as glutathione peroxidase (GSHPx), catalase, and superoxide dismutase (SOD). Cu–Zn, Mn–SOD, catalase, GSHPx, and GSH reductase (GR) are examples of enzymatic antioxidant systems that work by directly or sequentially removing ROS, which puts an end to their functions (Sheikha et al., 2022). Oxidative damage is induced by an imbalance linking oxidative powers and antioxidant defense systems. This imbalance has been linked to several disorders, including liver cirrhosis, diabetes, cancer, and atherosclerosis (Deepak et al., 2012; Mondal et al., 2020).

Chamomile is a plant that contains various bioactive compounds such as blue oil (0.24-1.9%) which has terpenoids, α-bisabolol, chamazulene, farnesene, spiro-ether sesquiterpene lactones, hydroxy coumarins, glycosides, flavonoids (apigenin, luteolin, patuletin, and quercetin), coumarins, and terpenoids. Due to its hepatoprotective, anti-inflammatory, anti-flatulence, anti-diarrheal, spasmolytic, laxative, diuretic, and antiepileptic properties, medieval Arab herbalists also recognized the plant's many traditional medicinal uses. Therapeutic plants used today. It is involved in the pharmacopeia of twenty-six nations (Sharifi-Rad et al., 2018). It's interesting to note that Germany named it “the medicinal plant of the year” in 1987. Many nations commercially grow chamomile to extract its blue essence, make herbal tea, and use it for medicinal and cosmetic purposes (Akram et al., 2024; Sharifi-Rad et al., 2018). Its flower apices and essential oils have been used as an antispasmodic, antibacterial, anti-inflammatory, and antiseptic properties (Akram et al., 2024).

The olive tree (Olea europaea L.) is an evergreen drought- and moderately salt-tolerant plant grown since antiquity for its oil and fruits in the Mediterranean. Olive leaves contain large amounts of phenolic chemicals, making them a rich source of added-value compounds with various health-promoting qualities. Indeed, extracts from olive leaves have strong scavenging and antioxidant properties, which makes them possibly useful for various uses (Žugčić et al., 2019). On the other hand, plants often contain phenolic chemicals in both bound and free forms. Because bound phenolic are covalently bonded to structural elements of cell walls, such as cellulose, hemicellulose, and pectin, they are often challenging to extract directly using conventional maceration techniques (Acosta-Estrada et al., 2014; Zeng et al., 2023)^. Various in vitro antioxidant experiments indicated that the unsolvable bound phenolic in various herbs exhibits much better antioxidant activity than free phenolic (Zhang et al., 2022). However, little attention has been devoted to the bound phenolic in olive leaves and their contributions to total phenolic and antioxidant activity because most research on olive leaves has concentrated exclusively on the antioxidant properties of free phenolic (Sharifi-Rad et al., 2018; Zhang et al., 2020). Ribociclib, a CDK4/6 inhibitor used in the treatment of breast cancer, has been linked to hepatotoxicity and may contribute to the development of HCC in rats. This study investigated the protective effect of Matricaria Chamomilla and Olive leaves extracts on liver damage caused by Ribociclib.

2. Methodology

2.1. Study design and data collection

I. Preparation of olive leaves extract

With a few modifications, olive leaf extract was prepared according to Al-Attar and Abu Zeid (2013). Seven liters of boiling water and 200 g of dried olive leaves were combined. After 3 h, the mixture was gently boiled for 30 min. After the boiling phase, the liquid was cooled to room temperature and gently mixed with an electric mixer for 20 min. The solution containing olive leaves was then filtered. To produce dried residues (active principles), the filtrate was evaporated in an oven at 40° C. The leaf extract yielded an average of 20.3% higher than the powdered samples. Furthermore, leaves were collected every 2 weeks and preserved in a refrigerator for further investigation (Al-Attar and Abu Zeid, 2013).

II. Chamomile oil

Chamomile (Matricaria chamomilla L.) oil was purchased from Sigma (Sigma Aldrich Chemical Co, USA). A concentration of 500 mg/kg per day of chamomile oil was mentioned (Aa et al., 2017; Perestrelo et al., 2022). As previously mentioned, Ribociclib powder was homogeneously distributed in a 0.1% carboxymethylcellulose (CMC) solution (Al-Shdefat et al., 2023).

III. Experimental design in Vivo

From the animal's home at Jordan University of Science and Technology in Irbid, Jordan, sixty adult male albino rats (9-10 weeks old) were purchased. Rats were randomly separated into fourth groups; each includes ten rats and an Acclimatization period of 3 days to 7 days temperature, a well-ventilated room, a 12-hour light/dark cycle at standard temperature, with unlimited access to drink and food ad libitum (Alsarhan et al., 2024). The IRB at the university approved this study and permitted the occurrence of the study. The following divides were made among the experimental groups (Alsarhan et al., 2024) (Scheme 1):

Scheme 1
Graphical scheme summarizing the experimental design, N: number of rats.

• Group A: The control group consisted of 10 rats with free access to rat pellets and orally administered saline as a placebo, considered the normal control (n=10).

• Group B: The positive control group consisted of 10 rats administrating 5 mg\kg Ribociclib daily.

• Group C: rats administrating 5 mg\kg Ribociclib (n=10) treated with 500 mg/kg/day of chamomile oil.

• Group D: rats administrating 5 mg\kg Ribociclib treated with 200 mg/kg/day of olive leaves extract.

Treatments: A daily dose of Ribociclib will be administered by gavage to rats in groups C and D. The daily dosage of chamomile (500 mg\kg group C) and olive leaves (200 mg\kg Group D) will be administered by gavage to rats in groups C and D. The rats were sacrificed after the experiment. Their livers were removed immediately. In all the animals, the liver was blocked for histological examination. The experiment was conducted in compliance with the guidelines of the animal ethics committee of JUST, which were expressed following international standard principles for laboratory animal use and care (NIH Publication No. 8023).

IV. Histology study

Remove the liver from the dissected rat. For light microscopy, livers were washed with PBS and fixed in 10% formal saline (Katrachanca and Koleske, 2017; Shebbo et al., 2020). Liver samples were sectioned using a manual rotary microtome (Leica RM2125RT, Leica Biosystems, Germany) and then dehydrated using increasing concentrations of ethanol. They were then cleaned with xylene alcohol, immersed in paraffin wax, and embedded in paraffin. Staining was performed with hematoxylin (HEMHP-OT-1L, BioGnost, Croatia) for 15 min and fixed with eosin Y 0.2% aqueous solution (EOY-02-OT-1L, BioGnost, Croatia) in DPX for 5 min (Munir et al., 2022).

The samples were then micro-photographed using inverted light microscopy (Leica Microsystems, Germany) equipped with a colored digital camera (Leica EC3, Switzerland) and manually monitored by computer software (Leica Application Suite LAS EZ version 1.8.0, Leica Microsystems, Switzerland) to capture the images (Alzbeede et al., 2021).

2.2. Blood chemistry

After the experiment was over, the serum was separated from the blood for biochemical analysis (centrifugation time: 3800 rpm/10 minutes; clotting time: 60 minutes at room temperature in dark situations). A Reflotron Clinical Chemistry Analyzer (Boehringer Mannheim, CT, USA) was used to measure the levels of cholesterol, LDL, triglycerides, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum samples obtained from both control and treated rats after the end of the experiments (Kumari et al., 2016). A Creatinine and Urea Analyzer (i-STAT® Blood Analysis System; (Abbott Point of Care, NJ, USA) was used to test heparinized blood (Kumari et al., 2016; Zhang et al., 2014, 2020)

2.3. Statistical analysis

The analysis was applied Graph Pad Prism 8 software (Graph Pad Software, San Diego, CA, USA). Regular distribution was evaluated using the D’Agostino-Pearson omnibus normality test. Parametric records were evaluated applying one-way ANOVA with Sidak’s post hoc and Dunnett test. Statistical significance was represented as follows: * for p < 0.01 and, ** for p < 0.05

3. Results

3.1. Biochemical laboratory analysis of liver and kidney

Tests for kidney function are shown in the research group’s creatinine and urea values (Figure 1). Urea concentration in rats treated with chamomile extracts (group C) was significantly lower than that of the control group A (p < 0.01; 0.000631). Conversely, Creatinine concentration in Ribociclib group B was significantly higher than that of the control group A (p < 0.05; 0.021706). However, there were no substantial variations (p < 0.05) between the control group and the creatinine concentration and chamomile oil or olive leaves extracts treatment groups (Figure 1).

Figure 1
(I) shows the effect of chamomile oil or olive leaf extracts of urea concentration in serum and (II) shows the effect of creatinine on kidney functions in Ribociclib-induced toxicity in rats (mean ± SE), N = 10. Group A: Control group; Group B: Ribociclib; Group C: Ribociclib and chamomile oil; and Group D: Ribociclib and olive leaves. *P < 0.01, **P < 0.05 compared with the control group

Furthermore, the levels of cholesterol and LDL in animals administered with Ribociclib and extracts showed a significant (p < 0.001) decrease compared with the control group (Figure 2). Moreover, the Ribociclib group (Group A) and Ribociclib + olive leaves group (Group D) showed a significant increase in the levels of TG at p < 0.05 and p < 0.01, respectively, compared to the control group. On the other hand, the Ribociclib and chamomile oil extract group (Group C) showed a high decrease in levels of TG at p < 0.01 compared to the control group (Figure 2).

Figure 2
(I) shows the effect of chamomile oil or olive leaf extracts of cholesterol levels in serum; (II) shows the effect on triglyceride levels; and (III) shows the effect on LDL levels in serum in rats (mean ± SE), N = 10. Group A: Control group, Group B: Ribociclib, Group C: Ribociclib and chamomile oil and Group D: Ribociclib and olive leaves. *P < 0.01, **P < 0.05 compared with the control group. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, Triglyceride (TG) and low-density lipoprotein (LDL).

Figure 3 reveals that the level of ALT is significantly high and has a vast distribution, as the p-value (0.014284) is lower than p < 0.05 (meanwhile the Ribociclib group had an increase in their ALT concentration compared with the control). Further on, in Figure 3, a significant difference (p < 0.01, 0.003249) was observed between the Ribociclib + chamomile group C and control groups. On the other hand, no major change in levels of ALT between the Ribociclib + olive leaves group D and control group A were noticed at p < 0.05 (Figure 3). However, the concentrations of AST showed very high significances in the Ribociclib (group B) (p < 0.01) (0.000165), Ribociclib + chamomile (Group C) (p < 0.01) (0.000992), and Ribociclib + olive leaves extract group (Group D) (p < 0.01) (0.000000291) which are higher than those depicted in Figure 3.

Figure 3
(I) shows the effect of chamomile oil or olive leaf extracts of ALT concentration in serum and (II) shows the effect of AST on Liver functions in Ribociclib-induced toxicity in rats (mean ± SE), N = 10. Group A: Control group; Group B: Ribociclib; Group C: Ribociclib and chamomile oil; and Group D: Ribociclib and olive leaves. *P < 0.01, **P < 0.05 compared with the control group.

3.2. Histopathological studies

According to the histopathological estimations of liver tissue (Figure 4A) Showed a normal histological structure of hepatocyte with normal sinusoids. While (Figure 4B) the rats that were demonstrated Ribociclib showed dilation of sinusoid, Pyknotic nuclei were seen in some necrotic hepatocytes, highly infiltration of the inflammation cell with congestion of the blood. The liver section of Ribociclib and chamomile oil group showed a mild improvement in the structure of the hepatocytes which was comparable to the control group they showed slightly dilation of sinusoid. Conversely, the liver tissues from rats that Ribociclib with olive leaves extract (Group D, Figure 4D) Showed infiltration of inflammatory cell, dilation of sinusoid with congestion of blood.

Figure 4
Images of liver sections for the experimental groups in this study stained with hematoxylin and eosin: (magnification × 40). Group A: Control group; Group B: Ribociclib; Group C: Ribociclib and chamomile oil; Group D: Ribociclib and olive leaves.

4. Discussion

Oxidative stress is caused by imbalances in producing reactive oxygen species inside cells and tissues and their accumulation. Cellular failure may result from reduced ATP production (mitochondria) elevated oxygen species (ROS) and oxidative stress (Kukreti et al., 2023; Yachamaneni and Dhanraj, 2017) Free radical production and removal out of balance would result in oxidative stress, which causes long-term aging, cell death (apoptosis), and oxidation of cell apparatuses (Jamshidzadeh et al., 2015; Lee et al., 2021). Oxidative stress affects many intracellular targets and cellular defense mechanisms such as glutathione storage. Lipid peroxidation is a typical consequence of oxidative stress and the generation of reactive oxygen species (ROS) in the liver (Jamshidzadeh et al., 2015).

The liver plays a crucial role in the body by maintaining various biological processes, including removing and detoxifying internal and external substances. Free radicals can also cause damage to cells by denaturing proteins, oxidizing unsaturated fatty acids, and interacting with carbohydrates and nucleic acids (Khan et al., 2012). Medicinal plants have long been used to treat liver diseases and serve as effective therapies. However, more scientific evidence is needed to support their benefits. Researchers worldwide collaborate to study the preventive effects of plant extracts against experimentally induced hepatotoxicity (Madrigal-Santillán et al., 2014).

Ribociclib is an important antineoplastic drug used in the treatment of breast cancer. It is metabolized by CYP3A4 in the liver and excreted through the biliary system. Neutropenia is the most common side effect of ribociclib. The phase III MONALEESA-2 study showed that 8.4% and 1.8% of patients in the ribociclib plus letrozole group developed grade 3 and 4 liver function abnormalities, respectively, compared with 2.4% and 2.4% in the letrozole plus placebo group (Fki et al., 2020). A recent investigation is examining the relationship between ribociclib and the development of hepatocellular carcinoma, a form of liver cancer that may arise as a result of exposure to the chemotherapeutic agent Ribociclib.

Ribociclib-induced liver and kidney toxicity served as an experimental technique to investigate the impact of extracts from Matricaria chamomilla and olive leaves extracts on hepatoprotective properties (Shebbo et al., 2020). Chamomile is a popular tea that has been shown to have hepatoprotective properties due to its phytochemicals, including essential oils, amino acids, flavonoids, polysaccharides, minerals, fatty acids, and other phenolic compounds (Madrigal-Santillán et al., 2014). Recent studies have shown that olive leaf extracts contain polyphenolic components, such as oleuropein and hydroxytyrosol (Fki et al., 2020) which are responsible for their hepatoprotective, hypolipidemic, and antioxidant properties (Al-Attar and Alsalmi, 2019). Chamomile Oil and Olive leaf extracts have been found to have hepatoprotective properties due to their antioxidant and antiproliferative effects.

Ribociclib-induced liver and kidney toxicity was used as an experimental technique to study the effects of chamomile extract and olive leaf extract on hepatoprotective properties (Shebbo et al., 2020). Chamomile is a popular tea that has been shown to have hepatoprotective properties due to its phytochemicals, including amino acids, polysaccharides, fatty acids, essential oils, minerals, flavonoids, and other phenolic compounds (Madrigal-Santillán et al., 2014). Recent studies have shown that olive leaf extract contains polyphenolic components such as oleuropein and hydroxytyrosol (Fki et al., 2020), which have hepatoprotective, hypolipidemic, and antioxidant properties (Al-Attar and Alsalmi, 2019). Chamomile oil and olive leaf extract have been found to have hepatoprotective properties due to their antioxidant and antiproliferative effects (Amani et al., 2020). The efficacy of the extracts in decreasing the elevated levels of serum enzymes brought on by Ribociclib treatment was utilized to evaluate their hepatoprotective capabilities. The investigated extracts facilitated a significant decrease in enzyme levels towards their respective normal values, demonstrating the maintenance of hepatocyte cell membrane integrity and the restoration of hepatic tissue injury provoked by Ribociclib.

Elevated serum levels of urea and creatinine are observed in Ribociclib-induced toxicity. Elevated levels may result from abnormal regulation of urea and creatinine causing renal damage, or may result from elevated levels, as demonstrated in the current study, which showed a significant increase in these levels in the Ribociclib group. The administration of Ribociclib and chamomile extract significantly decreased the levels of urea at p < 0.01 compared to the control group, indicating a protective effect of chamomile on the kidneys, whereas the creatinine concentration significantly increased in the Ribociclib group B compared with the control group at (p < 0.05).

Our results showed a significant increase in a Ribociclib-treated group compared with group A, p < 0.05. Furthermore, the group treated with the combination of Ribociclib and chamomile oil showed a significant increase compared to the control group, p < 0.01. However, AST concentrations were significantly higher in the Ribociclib group, Ribociclib, and chamomile oil group, and Ribociclib and olive leaves group compared to the control group (p < 0.01). Another finding of this study was that the administration of Group C (Ribociclib and chamomile oil) and Group D (Ribociclib + olive leaves) had a significant effect on serum cholesterol and LDL levels, with cholesterol in the animals compared to the control group. And LDL levels were reduced by p < 0.001. TG levels were significantly reduced in the Ribociclib and chamomile oil groups compared to the control group, p < 0.01. Therefore, it is recommended to monitor liver function before and during treatment and to develop a plan to manage possible liver toxicity. Our study also suggests strategies to treat hepatotoxicity (Munir et al., 2022; Schaeffer et al., 2023). Macroscopically, co-administrating Ribociclib with chamomile oil has been shown to have a preventive effect against Ribociclib-induced hepatotoxicity a phenomenon commonly seen in rat models characterized by irregular and nodular liver morpholy resulting from micro nodule formation. Furthermore, livers from the control group had homogeneous and superficial features. Subsequent, histology investigation of the liver of the Ribociclib group demonstrates sufficient mechanical damage.

The flowers of chamomile alone contain over 120 secondary metabolites, demonstrating the plant's high concentration of active metabolites (Mulinacci et al., 2000). The phytochemicals found in chamomile can be categorized primarily into four groups: coumarins, phenolic acids, flavonoids, terpenoids, and glucosides. Chamomile flowers contain between 0.24 and 2% essential oils. The blue hue of chamomile oil is commonly referred to as “blue oil.” The presence of sesquiterpenes and their derivatives, which make up 75-90% of the oil's composition, along with trace levels of monoterpenes is in fact responsible for the blue hue of chamomile oil. β-farnesene, farnesol, chamazulene, α-bisabolol, and α-bisabolol oxides A and B are a few examples of these molecules. It was discovered that chamazulene and (−)-α-bisabolol were two of these chemicals that were primarily responsible for the chamomile's healing, anti-inflammatory, antispasmodic, antibacterial, and ulcer-protective properties (El Joumaa and Borjac, 2022). Pharmacological studies revealed that M. chamomilla demonstrates a variety of biological properties, based on the several research papers have examined M. chamomilla anticancer activity in the literature. Its anti-proliferative properties have been demonstrated in both its methanolic and aqueous extracts. Significant reductions in cell viability were observed in a number of human cancer cell lines; they included cervical adenocarcinoma (by 58-60%), fibrosarcoma (by 70-75%), colon carcinoma (by 71-80%), breast carcinoma (by 50-60%), and metastatic prostate cancer (by 47.5-71%). M. chamomilla anticancer effects seem to be associated with necrosis and apoptosis as well as a reduction in the ability of cancerous cells to migrate and invade (El Joumaa and Borjac, 2022; El Mihyaoui et al., 2022).

The antioxidant properties of chamomile oil may have hepatoprotective effects by blocking the activation of Ribociclib, thereby preventing liver damage in rats. Chamomile is known for many health benefits, such as its anti-allergy and anti-cancer properties. The free radicals scavenging effects of chamomile are thought to protect the liver from damage caused by Ribociclib. They potentially prevent the interaction of lipid and peroxyl radicals with polyunsaturated fatty acids and impede the promotion of lipid peroxidation pathways (Ercisli and Orhan, 2007; Kaplowitz, 2002; Shareef et al., 2022).

5. Conclusion

The evidence for the potential hepatoprotective benefits of chamomile oil warrants further investigation. Chamomile oil significantly reduced serum cholesterol and LDL levels compared with the control group. Our results showed that co-administration of Ribociclib and chamomile oil had significant hepatoprotective effects against Ribociclib-induced liver injury in rats, as demonstrated by histological and biochemical parameters.

Acknowledgements

The authors thank the pharmacists who participated in this study.

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Publication Dates

• Publication in this collection
  21 Oct 2024
• Date of issue
  2024

History

• Received
  13 June 2024
• Accepted
  20 Aug 2024