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Full Research Article

Physiological Alterations in Hepatic Redox Homeostasis in Tumour-bearing Mice: Modulatory Effects of Convolvulus oxyphyllus Extract

A
Azhar Azher Al-Ankooshi1
A
Adnan Fayadh Sameer2
F
Farah Najim Al-deen Al-Nasrawi3
H
Halah Flaeeih Hasan1
A
Aseel Abdulsattar Husseind4
A
Ahmed Flayyih Hasan5,6,*
H
Hany M. El-Wahsh7
1Department of Physiology and Medical Physics, Faculty of Medicine, Jaber bin Hayyan University of Medical and Pharmaceutical Sciences, Najaf, Iraq.
2Ministry of Education, Baghdad Eductional Directorate/Al-Karkh II, Baghdad, Iraq.
3National Center of Hematology, Mustansiriyah University, Baghdad, Iraq.
4Department of Microbiology, College of Medicine, Mustansiriyah University, Iraq.
5Biotechnology Research Center, Al-Nahrain University, Baghdad, Iraq.
6Department of Medical Laboratory Techniques, College of Health and Medical Technology, Al-Farabi University, Baghdad, Iraq.
7Department of Marine Biology, Faculty of Marine Sciences, King Abdulaziz University, Saudi Arabia.

ABSTRACT

Background: Systemic metabolic load and redox imbalances are often associated with tumor burden and these conditions undoubtedly impair liver function. This research looked at how animals with ehrlich solid tumours (EST) altered their redox homeostasis and how Convolvulus oxyphyllus extract (COE) influenced these alterations.

Methods: Four groups of ten were randomly assigned to forty female swiss albino mice: Control, EST, EST COE (co-treatment) and EST → COE (Post-remedy). To learn more about the liver, we measured total protein, albumin and serum liver enzymes (ALT, AST and ALP). We examined hepatic redox markers, including catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA). To find structural alterations, a histological analysis was conducted.

Result: Mice with EST exhibited substantially reduced levels of albumin, total protein, SOD and CAT (P<0.05) and considerably higher levels of ALT, AST, ALP and MDA compared with controls. This indicates an imbalance between the liver’s capacity and redox homeostasis. Providing COE restored antioxidant enzyme activity and dramatically decreased oxidative stress indicators. Meanwhile, there were indications of improvement in blood chemistry indicators. Histological data, bolstered by biochemical effects, demonstrated reduced inflammation and hepatocyte degradation, particularly in the treated organisation. An extract of Convolvulus oxyphyllus changed how tumours affected liver function and redox homeostasis in mice. These results show that a redox-regulatory trait protects the liver from metabolic stress induced by cancer.

INTRODUCTION

The liver is the most important organ for controlling the body’s metabolism. It controls how much energy is used, how proteins are made, how toxins are removed and how the balance between oxidation and reduction is kept. When things are normal, there is a delicate balance between the production of reactive oxygen species (ROS) and antioxidant defence systems that maintains hepatic redox homeostasis (Al-Saeedi et al., 2026). It’s important to control the production of reactive oxygen species (ROS) to enable cells to communicate with one another. If this goes wrong for a long time, though, it could hurt cells and make them less stable. Tumour growth is now viewed as a systemic metabolic stressor rather than merely a localised growth phenomenon. Tumours that grow quickly need a lot of energy and biosynthesis, which can disrupt the metabolism of the organ they occupy, especially the liver (Porporato et al., 2016; Klover et al., 2004). In experimental models, including the ehrlich solid tumour (EST), changes in metabolic pathways and heightened mitochondrial activity lead to excessive production of reactive oxygen species (ROS), thereby inducing oxidative stress (Reuter et al., 2010; Al-Obaidi et al., 2022). Chronic oxidative stress may also exceed the frame’s intrinsic antioxidant defences, leading to lipid peroxidation, faded enzyme activity and alterations in liver characteristic indicators (Giannini et al., 2005; Al-Dulimi et al., 2025). Malondialdehyde (MDA) is not an unusual marker of cellular membrane damage because of oxidative stress. Superoxide dismutase (SOD) and catalase (CAT) are two important enzymes that protect cells from superoxide radicals and hydrogen peroxide. Changes in these markers can indicate how well the liver’s redox balance functions under stress. If this stability is off, it can cause infection and liver tissue damage. People need to research medicinal flowers rich in phenolic and flavonoid compounds, as these compounds can help maintain cellular balance and manage oxidative stress (Tousson et al., 2024; Mohammed et al., 2025). The secondary metabolites within the Convolvulus genus are recognised for their anti-inflammatory and antioxidant properties. We lack sufficient knowledge of how Convolvulus oxyphyllus alters the liver’s redox imbalance and the specific mechanisms underlying its tumour-promoting effects. This study aims to analyse changes in redox homeostasis in mice with EST and to evaluate the impact of convolvulus oxyphyllus extract on liver dysfunction associated with tumours, using biochemical and histological analyses.

MATERIALS AND METHODS

Plant material and authentication
 
Aerial parts (leaves and stems) of Convolvulus oxyphyllus were collected from Basiyah District, Al-Muthanna Desert, Al-Muthanna Governorate, Iraq, in February 2023. The plant material was identified and authenticated by a qualified botanist using standard taxonomic keys.
 
Animals used in experiments
 
Forty female Swiss albino mice weighing 20-22 grams were purchased from [National Cancer Institute-Cairo University-Egypt]. The animals were housed under standard laboratory conditions, including a 12-hour light/dark cycle at 22±2°C and were allowed unlimited access to food and water. The animals were acclimated for a week before the experiment.
 
Design of experiments
 
Four groups of mice (n = 10 per group) were randomly assigned:

• Group I (Control): Just the car was received.
 
• Group II (EST): given the vehicle and injected with Ehrlich tumour cells (Kamaraj et al., 2025).
 
• Group III (EST + COE, co-treatment): COE was administered for 14 days beginning on the day of tumour inoculation.
 
• Group IV (EST → COE, post-treatment): COE is administered for 14 days after the tumour has been allowed to develop for 7 days.
 
Identifying and administering the appropriate dosage
 
The COE dosage (15 mg/kg body weight/day) was consistent with OECD standards for acute oral toxicity and was based on previous research. A tube was used to give the extract orally after it was freshly reconstituted in distilled water each day to a final dosage volume of 10 mL/kg.
 
Ehrlich solid tumour (EST) induction
 
Serial intraperitoneal passages were used to preserve Ehrlich tumour cells, which were obtained from the National Cancer Institute in Cairo, Egypt. Using trypan blue exclusion, the number of viable cells was determined. A subcutaneous injection of 2.5-3.0 × 106 viable cells suspended in 0.2 mL of phosphate-buffered saline (PBS) was administered to the left thigh of each mouse.
 
Gathering samples of tissue and blood
 
The rats were given an intraperitoneal injection of sodium pentobarbital to induce anaesthesia at the conclusion of the experiment. Samples of blood were drawn from the inferior vena cava into non-heparinised tubes and the serum was separated by centrifugation. After being removed and cleaned in ice-cold saline, liver tissues were examined histologically and biochemically.
 
Biochemical assessment
 
We used commercial diagnostic kits to measure blood levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) according to the reitman-frankel method and the manufacturer’s instructions. Using a spectrophotometer, standard methods were used to measure serum albumin and total protein.
 
Hepatic redox parameter assessment
 
Before centrifuging the liver tissues for 15 minutes at 4°C, we mixed them with ice-cold phosphate-buffered saline (pH 7.4). Tests were conducted using the supernatant.
       
The thiobarbituric acid reactive substances (TBARS) test was used to measure the amount of malondialdehyde (MDA) that was present. We measured superoxide dismutase (SOD) activity using the misra and fridovich approach. The Aebi method was used to measure catalase (CAT) activity. The protein content of liver homogenates was determined using the Bradford technique. We measured enzyme activity in milligrams of protein.
 
Examination of histopathology
 
The liver tissues were washed, dried and embedded in paraffin after being stored for 24 to 48 hours in 10% neutral buffered formalin. For microscopic examination, 5 µm sections were cut using a rotary microtome and then stained with hematoxylin and eosin (H and E) (Alankooshi et al., 2023; Al-Hakeim et al., 2016).
 
Statistical evaluation
 
Every data point is shown as mean±SEM. IBM Corp., Armonk, NY, USA’s SPSS software (Version 26.0) was used to perform statistical analyses. After evaluating group differences using one-way analysis of variance (ANOVA), Tukey’s post hoc multiple-comparisons test was used. The threshold for statistical significance was set at a two-tailed P value of 0.05 or less.
 
Statement of ethics
 
Ethical approval was obtained under the consent obtained from Biotechnology Research Center/Al-Nahrain University.

RESULTS AND DISCUSSION

EST-induced hepatic damage
 
EST-caused liver injury
 
Blood levels of albumin and total protein dramatically dropped (P<0.05). In contrast, blood activities of ALT, AST and ALP significantly rose when EST and self-treated EST were compared to control mice (Table 1). However, compared to the EST and self-treated EST groups, the COE-treated Co-treated (COE+EST) and post-treated (EST+COE) mice exhibited a significant decrease in ALT, AST and ALP levels and a significant increase in albumin and t-protein levels; the ameliorated group was more noticeable in the post-treated group (Table 1).

Table 1: Variations in liver enzymes and functions in the studied groups.


 
Activity of antioxidant enzymes
 
When EST and self-treated EST liver homogenates were compared to control mice, MDA levels were significantly higher and GSH, SOD and CAT activities were significantly lower (Table 2).  However, comparing the EST+COE groups with the EST and self-treated EST groups showed substantial (P<0.05) reductions in MDA and significant (P<0.05) increases in SOD; the post-treated group showed a more pronounced ameliorative effect (Table 2).

Table 2: Effect of Convolvulus oxyphyllus extracts upon markers of oxidative stress in liver.


 
Liver histopathology
 
In the liver tissues of COE groups of animals, the histological changes from the control group revealed hepatocytes with eosinophilic cytoplasm, conspicuous round nuclei and a fine arrangement of Kupffer cells with a few spaced hepatic sinusoids between the hepatic cords (Fig 1 G1, G2). Additionally, COE showed significant tissue damage, including hepatic cord degeneration and noticeable inflammatory cells in liver tissues from EST-bearing mice and self-treated EST, along with pyknotic nuclei suggesting apoptosis, moderate fibrosis and widespread hepatocyte necrosis (Fig 1 G3). When EST mice were co-treated with COE, their liver sections showed mild damage and a noticeable recovery in all hepatocyte alterations (Fig 1 G4).

Fig 1: Liver histopathlogy.


       
An event that causes things to grow. Tumour burden significantly affects the function of host organs, especially those involved in metabolism, such as the liver (Ayala et al., 2014; Ighodaro et al., 2018; Obaid et al., 2025). The liver is very important for maintaining the body’s metabolism, removing toxins and regulating redox. As a result, tumours place significant strain on the body’s metabolism (Birben et al., 2012). The current study found that mice with EST had clear biochemical and histological signs of liver problems. The blood had more ALT, AST and ALP, but less albumin and total protein. Because of these changes, the membranes of liver cells are less stable and the liver isn’t producing as many proteins as it should. This makes sense with what we know about signs of liver damage (Razooki et al., 2025; Ahmeda et al., 2026).
       
Oxidative stress associated with tumours constitutes a significant molecular axis responsible for these alterations. When tumour cells grow quickly, their mitochondria are reprogrammed and their redox metabolism changes, leading to excessive reactive oxygen species (ROS) (Percie et al., 2020; Abd El-Rahmana et al., 2024). Reactive oxygen species (ROS) are essential for cellular signalling; however, excessive ROS can damage proteins, nucleic acids and lipid membranes (Ohkawa et al., 1979; Alankooshi et al., 2023). The increased hepatic MDA levels in mice with EST confirm lipid peroxidation and membrane damage. The body’s natural defences against free radicals are weakening because SOD and CAT levels have dropped significantly. Scientists agree that this difference between oxidative stress and antioxidant defence is a major reason why people with tumour organs fail (Alyasiri et al., 2025). Histopathology studies support the idea that redox causes harm. The inflammation, liver cell damage, sinusoid disruption and necrotic changes observed in EST animals are analogous to the mitochondrial damage and cell death induced by reactive oxygen species (ROS). Oxidative stress has been shown to initiate pathways that lead to inflammation and fibrosis, worsening tissue damage beyond the initial oxidative injury (Bradford et al., 1976; Al-Khuzaay et al., 2024). The biochemical and histological results of this study support the idea that the main reason EST-bearing mice have liver problems is that their bodies are out of balance with oxidative stress. Natural bioactive compounds rich in flavonoids and phenolics have attracted greater attention as potential means to rebalance redox and oxidative stress associated with tumours. People know that some species of Convolvulus produce secondary metabolites that are effective at fighting free radicals and reducing swelling (Percie et al., 2020; Hameed et al., 2025). The present study demonstrated that administration of Convolvulus oxyphyllus extract (COE) significantly reduced the elevated levels of malondialdehyde (MDA) and liver enzymes induced by EST. It also restored superoxide dismutase (SOD) and catalase (CAT) activity. The group that received treatment had a clearer path to recovery, suggesting that the redox-modulatory effect was more than just a way to stop the disease. Phenolic compounds safeguard cells by directly eliminating free radicals and modifying the functionality of antioxidant signalling pathways. The body’s system for fighting free radicals depends on NRF2, which stands for nuclear factor (erythroid-derived 2)-like 2 (Al-Saeedi et al., 2026). It controls the transcription of genes that encode enzymes that help cells eliminate toxins and protect them from damage. When NRF2 is activated, it restores redox balance, prevents lipid peroxidation and protects tissues from damage during pathological stress. This study did not immediately analyse NRF2 expression; however, the restoration of SOD and CAT activity to baseline levels post-COE treatment indicates that the frame’s intrinsic antioxidant mechanisms were enhanced rather than merely exhibiting a chemical antioxidant effect (Sies et al., 2020; Al-Obaidi et al., 2022). Controlled changes in oxidative stress are becoming a more likely option for cancer patients who have tried a lot of other treatments. Cancer cells need a very carefully controlled redox stability to keep growing without causing oxidative stress, which is bad. There are ways to restore the body’s redox balance to normal that don’t involve prolonging tumour survival, but they aren’t easy. The results of this study support the idea that COE might also protect the liver by boosting its antioxidant defences and reducing the oxidative damage caused by the tumour burden (Reczek et al., 2017; Hayes et al., 2014; Ahmed et al., 2025). The results show that tumour-induced oxidative stress is a major driver of liver problems in animals with EST. Convolvulus oxyphyllus extract safeguards the liver by regulating redox reactions. We should investigate the molecular mechanisms of antioxidant signalling pathways to understand better how these protective effects work and to develop COE as a more effective treatment for tumour-induced liver damage. One option is to look into NRF2 and the things it controls (Kashyap et al., 2021; Zhang et al., 2020; Al-Dulimi et al., 2025).

CONCLUSION

The recent findings indicate that tumour burden is associated with significant physiological disturbances in hepatic redox homeostasis and functional integrity in mice. The initiation of ehrlich solid tumours led to oxidative imbalance, diminished antioxidant defence and alterations in critical biochemical indicators of liver function, accompanied by structural changes in the liver. The management of Convolvulus oxyphyllus extract alleviated tumour-related disruptions by reducing lipid peroxidation and restoring antioxidant enzyme activities, crucially leading to concurrent enhancements in biochemical and histological parameters. The more significant large outcomes observed in the post-treatment business indicate a regulatory effect under recognised tumour-induced metabolic stress. These results support the hepatoprotective and redox-regulatory properties of Convolvulus oxyphyllus extract in tumour-bearing mice. Further molecular-stage investigations are essential to elucidate the regulatory pathways that control this physiological modulation.
 
Funding
 
None.

CONFLICT OF INTEREST

No conflict of interest exists between the authors.

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    Full Research Article

    Physiological Alterations in Hepatic Redox Homeostasis in Tumour-bearing Mice: Modulatory Effects of Convolvulus oxyphyllus Extract

    A
    Azhar Azher Al-Ankooshi1
    A
    Adnan Fayadh Sameer2
    F
    Farah Najim Al-deen Al-Nasrawi3
    H
    Halah Flaeeih Hasan1
    A
    Aseel Abdulsattar Husseind4
    A
    Ahmed Flayyih Hasan5,6,*
    H
    Hany M. El-Wahsh7
    1Department of Physiology and Medical Physics, Faculty of Medicine, Jaber bin Hayyan University of Medical and Pharmaceutical Sciences, Najaf, Iraq.
    2Ministry of Education, Baghdad Eductional Directorate/Al-Karkh II, Baghdad, Iraq.
    3National Center of Hematology, Mustansiriyah University, Baghdad, Iraq.
    4Department of Microbiology, College of Medicine, Mustansiriyah University, Iraq.
    5Biotechnology Research Center, Al-Nahrain University, Baghdad, Iraq.
    6Department of Medical Laboratory Techniques, College of Health and Medical Technology, Al-Farabi University, Baghdad, Iraq.
    7Department of Marine Biology, Faculty of Marine Sciences, King Abdulaziz University, Saudi Arabia.

    ABSTRACT

    Background: Systemic metabolic load and redox imbalances are often associated with tumor burden and these conditions undoubtedly impair liver function. This research looked at how animals with ehrlich solid tumours (EST) altered their redox homeostasis and how Convolvulus oxyphyllus extract (COE) influenced these alterations.

    Methods: Four groups of ten were randomly assigned to forty female swiss albino mice: Control, EST, EST COE (co-treatment) and EST → COE (Post-remedy). To learn more about the liver, we measured total protein, albumin and serum liver enzymes (ALT, AST and ALP). We examined hepatic redox markers, including catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA). To find structural alterations, a histological analysis was conducted.

    Result: Mice with EST exhibited substantially reduced levels of albumin, total protein, SOD and CAT (P<0.05) and considerably higher levels of ALT, AST, ALP and MDA compared with controls. This indicates an imbalance between the liver’s capacity and redox homeostasis. Providing COE restored antioxidant enzyme activity and dramatically decreased oxidative stress indicators. Meanwhile, there were indications of improvement in blood chemistry indicators. Histological data, bolstered by biochemical effects, demonstrated reduced inflammation and hepatocyte degradation, particularly in the treated organisation. An extract of Convolvulus oxyphyllus changed how tumours affected liver function and redox homeostasis in mice. These results show that a redox-regulatory trait protects the liver from metabolic stress induced by cancer.

    INTRODUCTION

    The liver is the most important organ for controlling the body’s metabolism. It controls how much energy is used, how proteins are made, how toxins are removed and how the balance between oxidation and reduction is kept. When things are normal, there is a delicate balance between the production of reactive oxygen species (ROS) and antioxidant defence systems that maintains hepatic redox homeostasis (Al-Saeedi et al., 2026). It’s important to control the production of reactive oxygen species (ROS) to enable cells to communicate with one another. If this goes wrong for a long time, though, it could hurt cells and make them less stable. Tumour growth is now viewed as a systemic metabolic stressor rather than merely a localised growth phenomenon. Tumours that grow quickly need a lot of energy and biosynthesis, which can disrupt the metabolism of the organ they occupy, especially the liver (Porporato et al., 2016; Klover et al., 2004). In experimental models, including the ehrlich solid tumour (EST), changes in metabolic pathways and heightened mitochondrial activity lead to excessive production of reactive oxygen species (ROS), thereby inducing oxidative stress (Reuter et al., 2010; Al-Obaidi et al., 2022). Chronic oxidative stress may also exceed the frame’s intrinsic antioxidant defences, leading to lipid peroxidation, faded enzyme activity and alterations in liver characteristic indicators (Giannini et al., 2005; Al-Dulimi et al., 2025). Malondialdehyde (MDA) is not an unusual marker of cellular membrane damage because of oxidative stress. Superoxide dismutase (SOD) and catalase (CAT) are two important enzymes that protect cells from superoxide radicals and hydrogen peroxide. Changes in these markers can indicate how well the liver’s redox balance functions under stress. If this stability is off, it can cause infection and liver tissue damage. People need to research medicinal flowers rich in phenolic and flavonoid compounds, as these compounds can help maintain cellular balance and manage oxidative stress (Tousson et al., 2024; Mohammed et al., 2025). The secondary metabolites within the Convolvulus genus are recognised for their anti-inflammatory and antioxidant properties. We lack sufficient knowledge of how Convolvulus oxyphyllus alters the liver’s redox imbalance and the specific mechanisms underlying its tumour-promoting effects. This study aims to analyse changes in redox homeostasis in mice with EST and to evaluate the impact of convolvulus oxyphyllus extract on liver dysfunction associated with tumours, using biochemical and histological analyses.

    MATERIALS AND METHODS

    Plant material and authentication
     
    Aerial parts (leaves and stems) of Convolvulus oxyphyllus were collected from Basiyah District, Al-Muthanna Desert, Al-Muthanna Governorate, Iraq, in February 2023. The plant material was identified and authenticated by a qualified botanist using standard taxonomic keys.
     
    Animals used in experiments
     
    Forty female Swiss albino mice weighing 20-22 grams were purchased from [National Cancer Institute-Cairo University-Egypt]. The animals were housed under standard laboratory conditions, including a 12-hour light/dark cycle at 22±2°C and were allowed unlimited access to food and water. The animals were acclimated for a week before the experiment.
     
    Design of experiments
     
    Four groups of mice (n = 10 per group) were randomly assigned:

    • Group I (Control): Just the car was received.
     
    • Group II (EST): given the vehicle and injected with Ehrlich tumour cells (Kamaraj et al., 2025).
     
    • Group III (EST + COE, co-treatment): COE was administered for 14 days beginning on the day of tumour inoculation.
     
    • Group IV (EST → COE, post-treatment): COE is administered for 14 days after the tumour has been allowed to develop for 7 days.
     
    Identifying and administering the appropriate dosage
     
    The COE dosage (15 mg/kg body weight/day) was consistent with OECD standards for acute oral toxicity and was based on previous research. A tube was used to give the extract orally after it was freshly reconstituted in distilled water each day to a final dosage volume of 10 mL/kg.
     
    Ehrlich solid tumour (EST) induction
     
    Serial intraperitoneal passages were used to preserve Ehrlich tumour cells, which were obtained from the National Cancer Institute in Cairo, Egypt. Using trypan blue exclusion, the number of viable cells was determined. A subcutaneous injection of 2.5-3.0 × 106 viable cells suspended in 0.2 mL of phosphate-buffered saline (PBS) was administered to the left thigh of each mouse.
     
    Gathering samples of tissue and blood
     
    The rats were given an intraperitoneal injection of sodium pentobarbital to induce anaesthesia at the conclusion of the experiment. Samples of blood were drawn from the inferior vena cava into non-heparinised tubes and the serum was separated by centrifugation. After being removed and cleaned in ice-cold saline, liver tissues were examined histologically and biochemically.
     
    Biochemical assessment
     
    We used commercial diagnostic kits to measure blood levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) according to the reitman-frankel method and the manufacturer’s instructions. Using a spectrophotometer, standard methods were used to measure serum albumin and total protein.
     
    Hepatic redox parameter assessment
     
    Before centrifuging the liver tissues for 15 minutes at 4°C, we mixed them with ice-cold phosphate-buffered saline (pH 7.4). Tests were conducted using the supernatant.
           
    The thiobarbituric acid reactive substances (TBARS) test was used to measure the amount of malondialdehyde (MDA) that was present. We measured superoxide dismutase (SOD) activity using the misra and fridovich approach. The Aebi method was used to measure catalase (CAT) activity. The protein content of liver homogenates was determined using the Bradford technique. We measured enzyme activity in milligrams of protein.
     
    Examination of histopathology
     
    The liver tissues were washed, dried and embedded in paraffin after being stored for 24 to 48 hours in 10% neutral buffered formalin. For microscopic examination, 5 µm sections were cut using a rotary microtome and then stained with hematoxylin and eosin (H and E) (Alankooshi et al., 2023; Al-Hakeim et al., 2016).
     
    Statistical evaluation
     
    Every data point is shown as mean±SEM. IBM Corp., Armonk, NY, USA’s SPSS software (Version 26.0) was used to perform statistical analyses. After evaluating group differences using one-way analysis of variance (ANOVA), Tukey’s post hoc multiple-comparisons test was used. The threshold for statistical significance was set at a two-tailed P value of 0.05 or less.
     
    Statement of ethics
     
    Ethical approval was obtained under the consent obtained from Biotechnology Research Center/Al-Nahrain University.

    RESULTS AND DISCUSSION

    EST-induced hepatic damage
     
    EST-caused liver injury
     
    Blood levels of albumin and total protein dramatically dropped (P<0.05). In contrast, blood activities of ALT, AST and ALP significantly rose when EST and self-treated EST were compared to control mice (Table 1). However, compared to the EST and self-treated EST groups, the COE-treated Co-treated (COE+EST) and post-treated (EST+COE) mice exhibited a significant decrease in ALT, AST and ALP levels and a significant increase in albumin and t-protein levels; the ameliorated group was more noticeable in the post-treated group (Table 1).

    Table 1: Variations in liver enzymes and functions in the studied groups.


     
    Activity of antioxidant enzymes
     
    When EST and self-treated EST liver homogenates were compared to control mice, MDA levels were significantly higher and GSH, SOD and CAT activities were significantly lower (Table 2).  However, comparing the EST+COE groups with the EST and self-treated EST groups showed substantial (P<0.05) reductions in MDA and significant (P<0.05) increases in SOD; the post-treated group showed a more pronounced ameliorative effect (Table 2).

    Table 2: Effect of Convolvulus oxyphyllus extracts upon markers of oxidative stress in liver.


     
    Liver histopathology
     
    In the liver tissues of COE groups of animals, the histological changes from the control group revealed hepatocytes with eosinophilic cytoplasm, conspicuous round nuclei and a fine arrangement of Kupffer cells with a few spaced hepatic sinusoids between the hepatic cords (Fig 1 G1, G2). Additionally, COE showed significant tissue damage, including hepatic cord degeneration and noticeable inflammatory cells in liver tissues from EST-bearing mice and self-treated EST, along with pyknotic nuclei suggesting apoptosis, moderate fibrosis and widespread hepatocyte necrosis (Fig 1 G3). When EST mice were co-treated with COE, their liver sections showed mild damage and a noticeable recovery in all hepatocyte alterations (Fig 1 G4).

    Fig 1: Liver histopathlogy.


           
    An event that causes things to grow. Tumour burden significantly affects the function of host organs, especially those involved in metabolism, such as the liver (Ayala et al., 2014; Ighodaro et al., 2018; Obaid et al., 2025). The liver is very important for maintaining the body’s metabolism, removing toxins and regulating redox. As a result, tumours place significant strain on the body’s metabolism (Birben et al., 2012). The current study found that mice with EST had clear biochemical and histological signs of liver problems. The blood had more ALT, AST and ALP, but less albumin and total protein. Because of these changes, the membranes of liver cells are less stable and the liver isn’t producing as many proteins as it should. This makes sense with what we know about signs of liver damage (Razooki et al., 2025; Ahmeda et al., 2026).
           
    Oxidative stress associated with tumours constitutes a significant molecular axis responsible for these alterations. When tumour cells grow quickly, their mitochondria are reprogrammed and their redox metabolism changes, leading to excessive reactive oxygen species (ROS) (Percie et al., 2020; Abd El-Rahmana et al., 2024). Reactive oxygen species (ROS) are essential for cellular signalling; however, excessive ROS can damage proteins, nucleic acids and lipid membranes (Ohkawa et al., 1979; Alankooshi et al., 2023). The increased hepatic MDA levels in mice with EST confirm lipid peroxidation and membrane damage. The body’s natural defences against free radicals are weakening because SOD and CAT levels have dropped significantly. Scientists agree that this difference between oxidative stress and antioxidant defence is a major reason why people with tumour organs fail (Alyasiri et al., 2025). Histopathology studies support the idea that redox causes harm. The inflammation, liver cell damage, sinusoid disruption and necrotic changes observed in EST animals are analogous to the mitochondrial damage and cell death induced by reactive oxygen species (ROS). Oxidative stress has been shown to initiate pathways that lead to inflammation and fibrosis, worsening tissue damage beyond the initial oxidative injury (Bradford et al., 1976; Al-Khuzaay et al., 2024). The biochemical and histological results of this study support the idea that the main reason EST-bearing mice have liver problems is that their bodies are out of balance with oxidative stress. Natural bioactive compounds rich in flavonoids and phenolics have attracted greater attention as potential means to rebalance redox and oxidative stress associated with tumours. People know that some species of Convolvulus produce secondary metabolites that are effective at fighting free radicals and reducing swelling (Percie et al., 2020; Hameed et al., 2025). The present study demonstrated that administration of Convolvulus oxyphyllus extract (COE) significantly reduced the elevated levels of malondialdehyde (MDA) and liver enzymes induced by EST. It also restored superoxide dismutase (SOD) and catalase (CAT) activity. The group that received treatment had a clearer path to recovery, suggesting that the redox-modulatory effect was more than just a way to stop the disease. Phenolic compounds safeguard cells by directly eliminating free radicals and modifying the functionality of antioxidant signalling pathways. The body’s system for fighting free radicals depends on NRF2, which stands for nuclear factor (erythroid-derived 2)-like 2 (Al-Saeedi et al., 2026). It controls the transcription of genes that encode enzymes that help cells eliminate toxins and protect them from damage. When NRF2 is activated, it restores redox balance, prevents lipid peroxidation and protects tissues from damage during pathological stress. This study did not immediately analyse NRF2 expression; however, the restoration of SOD and CAT activity to baseline levels post-COE treatment indicates that the frame’s intrinsic antioxidant mechanisms were enhanced rather than merely exhibiting a chemical antioxidant effect (Sies et al., 2020; Al-Obaidi et al., 2022). Controlled changes in oxidative stress are becoming a more likely option for cancer patients who have tried a lot of other treatments. Cancer cells need a very carefully controlled redox stability to keep growing without causing oxidative stress, which is bad. There are ways to restore the body’s redox balance to normal that don’t involve prolonging tumour survival, but they aren’t easy. The results of this study support the idea that COE might also protect the liver by boosting its antioxidant defences and reducing the oxidative damage caused by the tumour burden (Reczek et al., 2017; Hayes et al., 2014; Ahmed et al., 2025). The results show that tumour-induced oxidative stress is a major driver of liver problems in animals with EST. Convolvulus oxyphyllus extract safeguards the liver by regulating redox reactions. We should investigate the molecular mechanisms of antioxidant signalling pathways to understand better how these protective effects work and to develop COE as a more effective treatment for tumour-induced liver damage. One option is to look into NRF2 and the things it controls (Kashyap et al., 2021; Zhang et al., 2020; Al-Dulimi et al., 2025).

    CONCLUSION

    The recent findings indicate that tumour burden is associated with significant physiological disturbances in hepatic redox homeostasis and functional integrity in mice. The initiation of ehrlich solid tumours led to oxidative imbalance, diminished antioxidant defence and alterations in critical biochemical indicators of liver function, accompanied by structural changes in the liver. The management of Convolvulus oxyphyllus extract alleviated tumour-related disruptions by reducing lipid peroxidation and restoring antioxidant enzyme activities, crucially leading to concurrent enhancements in biochemical and histological parameters. The more significant large outcomes observed in the post-treatment business indicate a regulatory effect under recognised tumour-induced metabolic stress. These results support the hepatoprotective and redox-regulatory properties of Convolvulus oxyphyllus extract in tumour-bearing mice. Further molecular-stage investigations are essential to elucidate the regulatory pathways that control this physiological modulation.
     
    Funding
     
    None.

    CONFLICT OF INTEREST

    No conflict of interest exists between the authors.

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