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Egyptian Liver Journal
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Anti-inflammatory and antioxidant effect of Moringa oleifera against bisphenol-A-induced hepatotoxicity

Egyptian Liver Journal volume 12, Article number: 57 (2022) Cite this article

Abstract

Background

Non-pharmacological exposure or pharmacological drug-induced hepatic injury is the most common cause of hepatotoxicity. This study was conducted to evaluate the effect of Moringa oleifera leaf extract against bisphenol-A (BPA)-induced hepatic toxicity in rats.

Methods

Rats (n=56) were randomized into 7 groups (8 rats/each). Control groups: rats received olive oil or Moringa oleifera (400mg/kg) orally for 42 days. Hepatotoxicity groups: rats received BPA (50mg/kg BW) orally in a 1-ml olive oil for 42 days. Reversal groups: rats received Moringa oleifera (200 or 400mg/kg) and BPA (50mg/kg BW) for 42 days. Preventive groups: rats received Moringa oleifera (200 or 400mg/kg) for 30 days followed by BPA (50mg/kg BW) for 14 days. At the end of the experiments, blood samples were collected for glucose and liver function assay, while the liver tissue samples were collected and homogenated for measuring the inflammatory/oxidant and antioxidant markers.

Results

Rats with BPA-induced hepatotoxicity have significantly increased serum aspartate transaminase (AST), alanine transaminase (ALT), and glucose; liver lysate malondialdehyde (MDA); tumor necrosis factor (TNF-α); and macrophage migrating inhibitory factor (MIF) but significantly decreased levels of liver lysate reduced glutathione (GSH) and total antioxidant capacity (TAC) levels. The administration of Moringa oleifera (especially 400mg/kg BW) in both reversal and preventive groups ameliorate the toxic effects of BPA in rats, as it decreased the activities of AST, ALT, glucose, MDA, TNF-α, and MIF levels and increased the antioxidant levels of GSH and TAC.

Conclusion

Moringa oleifera has hepatoprotective effects against BPA-induced liver damage through the regulation of antioxidants and inflammatory biomarkers.

Introduction

Hepatotoxicity or injury of the liver is resulting from pharmacological or non-pharmacological agents that have a serious impact on health [1]. There are a variety of symptoms ranging from an elevation of liver enzymes without symptoms, sudden severe liver inflammation, persistent liver inflammation, and biliary obstruction to liver damage [2]. Drug-induced hepatic damage is the most common cause of hepatotoxicities such as non-steroid anti-inflammatory drugs, anti-tubercular drugs, anti-tumor drugs, hormonal, sedative and immune suppression, and neuropsychiatric drugs [1,2,3].

Bisphenol A (BPA) is an industrial chemical product [4] that affects humans from diet (BPA spreads from containers of food and drink during heating or washing), air, dust, water, and dental sealants [4]. High-dose exposure to BPA during pregnancy or lactation was accompanied by low birth weight, slow growth rate, decreased survival, and delayed puberty in offspring [5, 6]. BPA is a potential male fertility [7], and low-dose exposure to BPA was accompanied by insulin resistance in animal research [8]. There are limited epidemiological data on BPA effects in humans. In the US general population, adults are more liable to have diseases [9, 10]. BPA may be reacted with oxygen radicals, increased reactive oxygen species (ROS), H2O2, and lipid peroxide-oxidant malondialdehyde (MDA) productions and decreased antioxidant levels in the hepatic tissue with steatosis, liver tumors, and metabolic syndrome [5, 6, 9, 11].

A medicinal plant, Moringa oleifera, is a monogeneric family Moringaceae, leaf extract derived from a drumstick or horse radish or Shagara al Rauwaq tree in the Nile valley [12]. Moringa oleifera has an impressive range of medicinal uses with a high nutritional value containing protein, calcium, and potassium [12]. Also, rich sources of natural antioxidants such as ascorbic acid, flavonoids, phenolics, and β-carotene [12]. The extracts of Moringa oleifera leaves, seed, and pod have potent antidiabetic activity [13]. It plays an important role in treating an inflammatory and infectious disease affecting the heart, blood vessels, gastro-intestinal, liver, and kidney [14]. Moringa oleifera has a role in a regenerative and hepatoprotective activity, improved liver fibrosis in rats, reduced liver damage, decreased effect of chemical/pharmacological-induced hepatotoxicity, and reduced hepatic myeloperoxidase activity [15,16,17,18,19].

Therefore, the aim of this study was to evaluate the role of Moringa oleifera leaf extract against BPA-induced hepatotoxicity in rats.

Materials and methods

In this study, 56 male Wister adult albino rats (8 weeks of age, 150–200 g) were used and the experimental procedures were performed in the Faculty of Medicine, Menoufia University, Egypt. These experimental studies were conducted according to the ethical guidelines of the Animal Care and Use Committee of the Faculty of Medicine of Menoufia University, which followed the Guide for the Care and Use of Laboratory Animals.

Rats were kept and accommodated in standard plastic cages under controlled laboratory conditions of humidity (65%), temperature (22°C), and 12-h light/dark cycles. Rats had free access to water and were fed ad libitum on normal commercial chow. Rats were adjusted to the laboratory conditions for 10 days before conducting the experiment.

Bisphenol A (BPA) was demanded from Merck and Sigma-Aldrich Corporation (St Louis, Missouri, USA, CAS number 80-05-7). To have a concentration of 50 mg/kg body weight, BPA dissolved using 70% ethanol and then added to a 1-ml olive oil was used for oral administration [20]. Fresh green leaves of Moringa oleifera (2 kg) were obtained from a farm in Sadat City, Menoufia, Egypt (latitude 30.3597; longitude 30.4952) and then washed by distilled water to eject any debris and then kept till became dry at room temperature (22°C), and after that, it was ground into a powder [16]. The powder was dissolved with 70% ethanol for 2 days at 22°C and filtrated using a filter paper, then dried to form an extract powder [16, 21, 22]. The extract was autoclaved and stored in a steriled container at 4°C till it was needed. The component and compounds from Moringa oleifera extracts were phytochemically analyzed using liquid chromatography-mass spectrometry in our previous and other studies [16, 22].

Experimental design

Rats (n= 56) were used and randomized into 7 groups. Each group contained 8 rats in separate cages.

Control rats

Group 1: rats received a 1-ml olive oil orally for 42 days. Group 2 (M. oleifera group): rats received 400 mg/kg of M. oleifera orally in a 1-ml olive oil for 42 days [21].

Hepatotoxicity rats

Group 3 (BPA group): rats received 50 mg/kg body weight of BPA orally in a 1-ml olive oil for 42 days [20].

Reversal study

Group 4 (200 mg/kg of Moringa oleifera and BPA group): rats received 200 mg/kg of Moringa oleifera orally and 50 mg/kg of BPA orally in a 1-ml olive oil for 42 days [21]. Group 5 (400 mg/kg of Moringa oleifera and the BPA group): rats received 400 mg/kg of Moringa oleifera orally and 50 mg/kg of BPA orally in a 1-ml olive oil for 42 days.

Preventive study

Group 6 (200 mg/kg of Moringa oleifera followed by the BPA group): rats received 200 mg/kg of Moringa oleifera orally in a 1-ml olive oil for 30 days and then followed by 50 mg/kg of BPA orally in a 1-ml olive oil for 14 days. Group 7 (400 mg/kg of Moringa oleifera followed by the BPA group): rats received 400 mg/kg of Moringa oleifera orally in a 1-ml olive oil for 30 days and then followed by 50 mg/kg of BPA orally in a 1-ml olive oil for 14 days.

Blood and liver tissue analysis

Rats were given diethyl ether anesthetics. Blood samples were obtained from the orbital venous plexus of all groups on day 45. The blood was centrifuged, and the serum was collected and refrigerated at −20°C till used for blood glucose and liver function tests. The liver tissues of rats were isolated and washed with PBS pH 7.4 and 0.16 mg/ml heparin to remove RBCs and clots. The liver tissue was homogenized in a 2-ml cold RIPA buffer (Thermo Fisher Scientific, Rockford, Illinois, USA, Catalog Number 89900) and centrifuged at 4000 rpm for 15 min at 4°C. The supernatant was obtained and refrigerated at −80 °C until used for inflammatory/oxidant and antioxidant markers.

Blood glucose and liver function tests

The blood sample for random blood glucose was assessed based on the glucose oxidase-peroxidase chromogen system using colorimetric kits (Bio-Diagnostics Ltd., Dokki, Giza, Egypt, Catalog Number GL 13 20) according to the manufacturer’s procedure. Serum liver enzyme alanine aminotransferase (ALT) (EC2.6.1.2) and aspartate aminotransferase (AST) (EC2.6.1.1) [23] were assessed using colorimetric kits (Diamond Diagnostics, Cairo, Egypt) according to the manufacturer’s procedure.

Hepatic inflammatory oxidant

Liver homogenate for inflammatory lipid peroxide malondialdehyde (MDA) (the production of thiobarbituric acid reactive substances, TBARS) was analyzed using colorimetric kits (Bio-Diagnostics Ltd., Dokki, Giza, Egypt, Catalog Number MD 25 29) [24, 25].

Hepatic inflammatory cytokines

Tumor necrosis factor-alpha (TNF-α) (RayBiotech Inc. Parkway, LaneSuiteNorcross, Georgia, USA, Catalog Number ELR-TNFa-1) [17] and macrophage migration inhibitory factor (MIF) (R&D system, Minneapolis, Minnesota, USA, Catalog number DY1978) [26, 27] were assessed using enzyme-linked immunosorbent assay (ELISA) kits according to manufacturer’s procedure.

Hepatic antioxidants

Liver homogenate of antioxidant-reduced glutathione (GSH) was assessed using colorimetric kits (Bio-Diagnostics Ltd., Dokki, Giza, Egypt, Catalog Number GR 25 11) [17]. Also, liver homogenate of total antioxidant capacity (TAC) was measured using colorimetric kits (Bio-Diagnostics Ltd., Dokki, Giza, Egypt, Catalog Number TA 25 13) [28, 29].

Statistical analysis

All parameters were presented as mean ± standard error mean (SEM) using the statistical analysis system program (SPSS), version 20 (IBM®, USA). Data were analyzed by one-way analysis of variance (ANOVA) followed by post hoc test to determine the significant differences. P < 0.05 was considered significant.

Results

Effect of Moringa oleifera on liver function test in BPA-induced hepatotoxicity rats

Treatment of rats with Moringa oleifera resulted in a non-significant increase in serum AST concentration as compared to control rats (28.75 ± 2.76 vs 21.00 ± 2.13 U/l, P > 0.05). Treatment of rats with BPA resulted in a significant increase in serum AST concentration as compared to control rats (240.56 ± 24.61 vs 21.00 ± 2.13 U/l, P < 0.001). AST concentrations were significantly changes in reversal study with 400 mg/kg of Moringa oleifera (107.0 ± 21.39 U/l, P = 0.003) and prevention study with 400 mg/kg of Moringa oleifera (102.63 ± 25.23 U/l, P = 0.002) compared with BPA-treated rats (Fig. 1A).

Fig. 1
figure 1

Effect of Moringa oleifera on liver function test in BPA-induced hepatotoxicity rats. Serum aspartate transaminase (AST, A) and alanine transaminase (ALT, B) levels were assessed in all groups. All data were presented as mean ± SEM. n= 8 rats/group, BPA = bisphenol-A (50 mg/kg BW). M1 Moringa oleifera (200 mg/kg BW); M2 Moringa oleifera (400 mg/kg BW); P < 0.05 was considered significant. NS non- significant, P > 0.05

Full size image

Treatment of rats with Moringa oleifera resulted in a non-significant increase in serum ALT concentration as compared to control rats (21.28 ± 1.82 vs 17.88 ± 1.80 U/l, P > 0.05). Treatment of rats with BPA resulted in a significant increase in serum ALT concentration as compared to control rats (71.14 ± 6.55 vs 17.88 ± 1.80 U/l, P < 0.001). ALT concentrations were significantly changes in reversal study with 400 mg/kg of Moringa oleifera (34.33 ±12.60 U/l, P = 0.038) and prevention study with 400 mg/kg of Moringa oleifera (33.43 ± 7.11 U/l, P = 0.025) compared with BPA-treated rats (Fig. 1B).

Effect of Moringa oleifera on serum glucose level in BPA-induced hepatotoxicity rats

Treatment of rats with Moringa oleifera resulted in a non-significant increase in serum glucose concentration as compared to control rats (125.50 ± 4.63 vs 121.36 ± 5.22 mg/dl, P > 0.05). Treatment of rats with BPA resulted in a significant increase in serum glucose concentration as compared to control rats (243.23 ± 25.74 vs 121.36 ± 5.22 mg/dl, P < 0.001). Serum glucose concentrations were reduced in reversal study with 400 mg/kg of Moringa oleifera (175.42 ± 16.27 mg/dl, P = 0.019) and prevention study with 400 mg/kg of Moringa oleifera (176.45 ± 17.23 mg/dl, P = 0.056) compared with BPA-treated rats (Fig. 2A).

Fig. 2
figure 2

Effect of Moringa oleifera on serum glucose level and lipid oxidant malondialdehyde in BPA-induced hepatotoxicity rats. Serum glucose (A) and hepatic malondialdehyde (MDA, B) levels were assessed in all groups. All data were presented as mean ± SEM. n= 8 rats/group, BPA bisphenol-A (50 mg/kg BW). M1 Moringa oleifera (200 mg/kg BW); M2 Moringa oleifera (400 mg/kg BW); P < 0.05 was considered significant. NS non-significant, P > 0.05

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Effect of Moringa oleifera on liver lysate MDA level in BPA-induced hepatotoxicity rats

There was no difference in hepatic MDA concentrations between Moringa oleifera and control rats (2.07 ± 0.47 vs 2.19 ± 0.46 nmol/ml; P < 0.05). Hepatic MDA concentrations were significantly higher in BPA-treated rats compared with control rats (3.93 ± 0.50 vs 2.19 ± 0.46 nmol/ml; P < 0.001). Hepatic MDA concentrations were significantly reduced in reversal study with 400 mg/kg of Moringa oleifera (1.86 ± 0.16 nmol/ml, P = 0.008) and prevention study with 400 mg/kg of Moringa oleifera (1.46 ± 0.14 nmol/ml, P = 0.001) compared with BPA-treated rats (Fig. 2B).

Effect of Moringa oleifera on antioxidant activity of liver tissue GSH and TAC levels in BPA-induced hepatotoxicity rats

Treatment of rats with Moringa oleifera resulted in non-significant decrease in hepatic GSH concentration as compared to control rats (1.30 ± 0.09 vs 1.73 ± 0.15 mg/dl, P > 0.05). Hepatic GSH concentrations were non-significantly lower in BPA-treated rats compared with control rats (0.94 ± 0.13 vs 1.73 ± 0.15 mg/dl; P = 0.062). Hepatic GSH concentrations were increased in reversal study with 400 mg/kg of Moringa oleifera (1.54 ± 0.08 mg/dl, P = 0.358) and prevention study with 400 mg/kg of Moringa oleifera (2.82 ± 0.70 mg/dl, P < 0.001) compared with BPA-treated rats. However, treatment of rats with 400 mg/kg of Moringa oleifera resulted in a significant increase in hepatic GSH concentration as compared to the prevention study (P < 0.001) (Fig. 3A).

Fig. 3
figure 3

Effect of Moringa oleifera on antioxidant activity of the liver tissue in BPA-induced hepatotoxicity rats. Hepatic-reduced glutathione (GSH, A) and total antioxidant capacity (TAC, B) levels were assessed in all groups. All data were presented as mean ± SEM. n= 8 rats/group, BPA bisphenol-A (50 mg/kg BW). M1 Moringa oleifera (200 mg/kg BW); M2 Moringa oleifera (400 mg/kg BW); P < 0.05 was considered significant. NS non-significant, P > 0.05

Full size image

Treatment of rats with Moringa oleifera resulted in a non-significant increase in hepatic TAC concentration as compared to control rats (4.77 ± 0.33 mmol/L vs 4.58 ± 0.14 mmol/L, P>0.05), BPA (P<0.001), and reversal and prevention study (P = 0.002). Hepatic TAC concentrations were non-significantly lower in BPA-treated rats compared with control rats (1.98 ± 0.29 vs 4.58 ± 0.14 mmol/L; P < 0.001). Hepatic TAC concentrations were non-significantly increased in the reversal study with 400 mg/kg of Moringa oleifera (3.30 ± 0.05 mmol/L, P = 0.069) and prevention study with 400 mg/kg of Moringa oleifera (3.31 ± 0.16 mmol/L, P=0.10) compared with BPA-treated rats. However, treatment of rats with 400 mg/kg of Moringa oleifera resulted in a significant increase in hepatic TAC concentration as compared to BPA (P < 0.001) and both reversal and prevention studies (P = 0.002) (Fig. 3B).

Effect of Moringa oleifera on the inflammatory activity of liver tissue TNF-α and MIF levels in BPA-induced hepatotoxicity rats

There was no difference in hepatic TNF-α concentrations between Moringa oleifera and control rats (16.83 ± 0.33 vs 16.63 ± 0.23 pg/ml; P > 0.05). Hepatic TNF-α concentrations were significantly higher in BPA-treated rats compared with control rats (48.21 ± 2.91 vs 16.63 ± 0.23 pg/ml; P < 0.001). Hepatic TNF-α concentrations were significantly reduced in reversal study with 400 mg/kg of Moringa oleifera (24.41 ± 1.70 pg/ml, P < 0.001) and prevention study with 400 mg/kg of Moringa oleifera (22.11 ± 1.26 pg/ml, P < 0.001) compared with BPA-treated rats. Moreover, treatment of rats with 400 mg/kg of Moringa oleifera resulted in a significant decrease in hepatic TNF-α concentration as compared to BPA (P < 0.001) and both reversal and prevention studies (P < 0.001) (Fig. 4A).

Fig. 4
figure 4

Effect of Moringa oleifera on the inflammatory activity of the liver tissue in BPA-induced hepatotoxicity rats. Hepatic tumor necrosis factor (TNF-α, A) and macrophage migrating inhibitory factor (MIF, B) levels were assessed in all groups. All data were presented as mean ± SEM. n= 8 rats/group, BPA bisphenol-A (50 mg/kg BW). M1 Moringa oleifera (200 mg/kg BW); M2 Moringa oleifera (400 mg/kg BW); P < 0.05 was considered significant. NS non-significant, P > 0.05

Full size image

There was no difference in hepatic MIF concentrations between Moringa oleifera and control rats (14.27 ± 0.37 vs 14.94 ± 0.47 ng/ml; P > 0.05). Hepatic MIF concentrations were significantly higher in BPA-treated rats compared with control rats (24.38 ± 2.29 vs 14.94 ± 0.47 ng/ml; P < 0.001). Hepatic MIF concentrations were significantly reduced in reversal study with 400 mg/kg of Moringa oleifera (17.09 ± 0.47 ng/ml, P < 0.001) and prevention study with 400 mg/kg of Moringa oleifera (12.64 ± 0.14 ng/ml, P < 0.001) compared with BPA-treated rats. Moreover, treatment of rats with 400 mg/kg of Moringa oleifera resulted in a significant decrease in hepatic MIF concentration as compared to BPA (P < 0.001) and reversal study (P = 0.004) (Fig. 4B).

Discussion

Destruction of the liver tissue by pharmacological or non-pharmacological substances causes hepatotoxicity [2, 17]. Hepatic damage by a pharmacological agent usually presents in many ways as acute or chronic hepatic disorders or cholestasis or both [30]. This may be affected by many factors such as age, sex, alcohol intake, cigarette smoking, drug intake, genetic factors, environmental factor, and other hepatic disorders [2, 30].

BPA is a chemical substance that mimics or blocks the receptors and alters hormone concentrations and its metabolism [4, 7, 8]. BPA stimulates cellular responses and affects body functions even in small concentrations [6, 9]. BPA can induce apoptosis in the hepatocytes in the hepatic sections of the BPA-treated rats [6]. The BPA induced an increase in ROS production and reduction of antioxidant activity [5, 11, 31].

Therefore, the present study was to evaluate the effect of Moringa oleifera leaf extract as a medicinal plant against BPA-induced liver damage in rats.

The current study revealed that rats with BPA had hepatic toxicity and damage with significantly higher AST and ALT activities that matched with other studies [11, 32]. BPA exposure enhanced the production of ROS and inhibited the activities of antioxidant enzymes [25, 31]. This may be attributed to BPA-induced inflammatory oxidative damage to the liver and releasing hepatic enzymes into the blood [8, 32].

Moringa oleifera (200 and 400 mg/kg BW) either with BPA (reversal groups) or 1 month before BPA (preventive groups) reduced activities of serum AST and ALT. Our results agreed with other study showed that having moringa decreased the toxic effects of CCL4- on serum levels of liver enzymes [16], reported that the moringa has a part in maintaining the liver cell membrane complete and so on no leakage of enzymes into blood [16].

In the present results, there was a significantly higher serum level of blood sugar in rats that received BPA compared to the control group. This observation was similar to other studies which reported that BPA exposure led to hyperglycemia [9, 33]. BPA-induced hyperglycemia may be associated with oxidative stress [4, 33] and increased lipid peroxidation; thus, they disrupt the serum glucose regulation [34].

In the current results, there was a significant lower serum level of blood sugar in rats received by BPA with or after Moringa oleifera leaf extract at doses 200 and 400 mg/kg of BW. This result was matched with other study illustrated that Moringa oleifera leaves help glucose uptake by the liver, so reduction of serum glucose levels [35].

In our results, there was a significant elevation of lipid peroxidation biomarker (MDA) and a significant reduction of antioxidant biomarkers GSH and TAC. These findings agreed with other studies [11, 24, 31, 36]. BPA-toxic metabolites caused oxidized glutathione and reduced GSH levels [34, 37]. Moreover, MDA and 4-hydroxynonenal have the ability to change of enzymes of mitochondria and decrease the glutathione [38], which might suppress the GSH/GSSG ratio and this led to hepatocellular damage.

Our data showed the improvement effect of Moringa oleifera in treated and prophylactic against BPA represented by decreased MDA concentrations and increased GSH and TAC concentrations. These results are similar to other studies [18] showed the level of MDA was reduced and GSH was restored in moringa-treated animals compared to the groups induced with acetaminophen [17, 19]. Moringa oleifera has a cellular protection effect due to its content of phenol substances [14]. These phenol substances have protection roles against inflammation and liver cell damage [17, 39].

Our concurrent study revealed that BPA intoxication led to a significant increase in inflammatory biomarkers TNF-α and MIF. These findings agreed with other studies which demonstrated that elevation of BPA concentrations in the blood is associated with elevated concentrations of TNF-α proinflammatory cytokines [25, 33, 40, 41]. MIF is a multipotent cytokine mediator in hepatotoxic as pro-oxidant and proinflammatory and profibrotic effects [42] in thioacetamide-induced liver injury [27], ethanol-induced liver injury [26], cytotoxic-T-lymphocyte (CTL)-induced acute hepatitis [43], and acute liver injury [44].

Oral administration of Moringa oleifera to BPA rats decreased the level of TNF-α and MIF, and this finding agreed with other studies [45]. Also, a perfect response after the therapy of Moringa oleifera leaves and in the prophylactic group showed a significant reduction in TNF-α levels [45] via antioxidant and anti-inflammatory activities [15, 16, 20,21,22].

Finally, taken together, Moringa oleifera leaves have an important value in the prevention of liver damage, oxidation, and toxicity. Furthermore, it may help in the reduction of liver enzymes to baseline concentration, decrease oxidative stress, and increase hepatic anti-oxidant/anti-inflammatory protein contents [16,17,18].

Conclusion

Administration of BPA can cause hepatotoxicity. These toxicities may be related to its TNF-α and MIF-mediated hepatic damage and release of aminotransferases. Also, it causes abnormalities in blood sugar and lipid profile (MDA) associated with a reduction in GSH and TAC which are antioxidants. In contrast, pre- and conjunction administration of Moringa oleifera with BPA toxicity altered its toxicity on liver function and protect it from damage. Thus, Moringa oleifera had to improve and protect the effects against BPA-induced hepatotoxicity by regulation of antioxidants and inflammatory biomarkers.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALT:

Alanine transaminase

AST:

Aspartate transaminase

BPA:

Bisphenol-A

CCl4:

Carbon tetrachloride

ELISA:

Enzyme-linked immunosorbent assay

GSH:

Reduced glutathione

M. oleifera :

Moringa oleifera

MDA:

Malondialdehyde

MIF:

Macrophage migrating inhibitory factor

NSAIDs:

Non-steroid anti-inflammatory drugs

ROS:

Reactive oxygen species

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor

References

  1. Hassan A, Fontana RJ (2019) The diagnosis and management of idiosyncratic drug-induced liver injury. Liver Int 39(1):31–41

    Article  CAS  PubMed  Google Scholar 

  2. Alempijevic T, Zec S, Milosavljevic T (2017) Drug-induced liver injury: do we know everything? World J Hepatol 9(10):491–502

    Article  PubMed  PubMed Central  Google Scholar 

  3. Moore N, Pollack C, Butkerait P (2015) Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 11:1061–1075

    PubMed  PubMed Central  Google Scholar 

  4. Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV (2007) Human exposure to bisphenol A (BPA). Reprod Toxicol 24(2):139–177

    Article  CAS  PubMed  Google Scholar 

  5. Vahdati Hassani F, Abnous K, Mehri S, Jafarian A, Birner-Gruenberger R, Yazdian Robati R et al (2018) Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: mechanism of hepatotoxicity and biomarker discovery. Food Chem Toxicol 112:26–38

    Article  CAS  PubMed  Google Scholar 

  6. Elswefy SE, Abdallah FR, Atteia HH, Wahba AS, Hasan RA (2016) Inflammation, oxidative stress and apoptosis cascade implications in bisphenol A-induced liver fibrosis in male rats. Int J Exp Pathol 97(5):369–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Radwan M, Wielgomas B, Dziewirska E, Radwan P, Kaluzny P, Klimowska A et al (2018) Urinary bisphenol A levels and male fertility. Am J Mens Health 12(6):2144–2151

    Article  PubMed  PubMed Central  Google Scholar 

  8. Batista TM, Alonso-Magdalena P, Vieira E, Amaral ME, Cederroth CR, Nef S et al (2012) Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice. PLoS One 7(3):e33814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Song S, Zhang L, Zhang H, Wei W, Jia L (2014) Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring. Int J Environ Res Public Health 11(4):3728–3742

    Article  PubMed  PubMed Central  Google Scholar 

  10. Clayton EM, Todd M, Dowd JB, Aiello AE (2011) The impact of bisphenol A and triclosan on immune parameters in the U.S. population, NHANES 2003-2006. Environ Health Perspect 119(3):390–396

    Article  CAS  PubMed  Google Scholar 

  11. Eweda SM, Newairy ASA, Abdou HM, Gaber AS (2020) Bisphenol A-induced oxidative damage in the hepatic and cardiac tissues of rats: the modulatory role of sesame lignans. Exp Ther Med 19(1):33–44

    CAS  PubMed  Google Scholar 

  12. Anwar F, Latif S, Ashraf M, Gilani AH (2007) Moringa oleifera: a food plant with multiple medicinal uses. Phytother Res 21(1):17–25

    Article  CAS  PubMed  Google Scholar 

  13. Al-Malki AL, El Rabey HA (2015) The antidiabetic effect of low doses of Moringa oleifera Lam. seeds on streptozotocin induced diabetes and diabetic nephropathy in male rats. Biomed Res Int 2015:381040

    Article  PubMed  PubMed Central  Google Scholar 

  14. Karthivashan G, Tangestani Fard M, Arulselvan P, Abas F, Fakurazi S (2013) Identification of bioactive candidate compounds responsible for oxidative challenge from hydro-ethanolic extract of Moringa oleifera leaves. J Food Sci 78(9):C1368–C1375

    Article  CAS  PubMed  Google Scholar 

  15. Hamza AA (2010) Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats. Food Chem Toxicol 48(1):345–355

    Article  CAS  PubMed  Google Scholar 

  16. Mousa AA, El-Gansh HAI, Eldaim MAA, Mohamed MAE, Morsi AH, El Sabagh HS (2019) Protective effect of Moringa oleifera leaves ethanolic extract against thioacetamide-induced hepatotoxicity in rats via modulation of cellular antioxidant, apoptotic and inflammatory markers. Environ Sci Pollut Res Int 26(31):32488–32504

    Article  PubMed  Google Scholar 

  17. Abdel Fattah ME, Sobhy HM, Reda A, Abdelrazek HMA (2020) Hepatoprotective effect of Moringa oleifera leaves aquatic extract against lead acetate-induced liver injury in male Wistar rats. Environ Sci Pollut Res Int 27(34):43028–43043

    Article  CAS  PubMed  Google Scholar 

  18. El-Hadary AE, Ramadan MF (2019) Antioxidant traits and protective impact of Moringa oleifera leaf extract against diclofenac sodium-induced liver toxicity in rats. J Food Biochem 43(2):e12704

    Article  PubMed  Google Scholar 

  19. Fakurazi S, Hairuszah I, Nanthini U (2008) Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. Food Chem Toxicol 46(8):2611–2615

    Article  CAS  PubMed  Google Scholar 

  20. Fawzy EI, El Makawy AI, El-Bamby MM, Elhamalawy HO (2018) Improved effect of pumpkin seed oil against the bisphenol-A adverse effects in male mice. Toxicol Rep 5:857–863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sharifudin SA, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P (2013) Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats. Pharm Biol 51(3):279–288

    Article  PubMed  Google Scholar 

  22. Sinha M, Das DK, Datta S, Ghosh S, Dey S (2012) Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract. Indian J Exp Biol 50(3):209–215

    PubMed  Google Scholar 

  23. Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63

    Article  CAS  PubMed  Google Scholar 

  24. Kim JH, Hong YC (2017) Increase of urinary malondialdehyde level by bisphenol A exposure: a longitudinal panel study. Environ Health 16(1):8

    Article  PubMed  PubMed Central  Google Scholar 

  25. Moon MK, Kim MJ, Jung IK, Koo YD, Ann HY, Lee KJ et al (2012) Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level. J Korean Med Sci 27(6):644–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Barnes MA, McMullen MR, Roychowdhury S, Pisano SG, Liu X, Stavitsky AB et al (2013) Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology 57(5):1980–1991

    Article  CAS  PubMed  Google Scholar 

  27. Vukicevic D, Rovcanin B, Gopcevic K, Stankovic S, Vucevic D, Jorgacevic B et al (2021) The role of MIF in hepatic function, oxidative stress, and inflammation in thioacetamide-induced liver injury in mice: protective effects of betaine. Curr Med Chem 28(16):3249–3268

    Article  CAS  PubMed  Google Scholar 

  28. Salehi-Sahlabadi A, Mokari A, Elhamkia M, Farahmand F, Jabbari M, Hekmatdost A (2020) Dietary total antioxidant capacity and risk of non-alcoholic fatty liver disease: a case-control study. J Res Health Sci 20(3):e00486

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wang JH, Lee SB, Lee DS, Son CG (2021) Total antioxidant capacity in HBV carriers, a promising biomarker for evaluating hepatic fibrosis: a pilot study. Antioxidants (Basel) 10(1):77

    Article  CAS  Google Scholar 

  30. Andrade RJ, Robles M, Fernandez-Castaner A, Lopez-Ortega S, Lopez-Vega MC, Lucena MI (2007) Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists. World J Gastroenterol 13(3):329–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang H, Yang R, Shi W, Zhou X, Sun S (2022) The association between bisphenol A exposure and oxidative damage in rats/mice: a systematic review and meta-analysis. Environ Pollut 292(Pt B):118444

    Article  CAS  PubMed  Google Scholar 

  32. Zaulet M, Kevorkian SEM, Dinescu S, Cotoraci C, Suciu M, Herman H et al (2017) Protective effects of silymarin against bisphenol A-induced hepatotoxicity in mouse liver. Exp Ther Med 13(3):821–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moghaddam HS, Samarghandian S, Farkhondeh T (2015) Effect of bisphenol A on blood glucose, lipid profile and oxidative stress indices in adult male mice. Toxicol Mech Methods 25(7):507–513

    Article  CAS  PubMed  Google Scholar 

  34. Indumathi D, Jayashree S, Selvaraj J, Sathish S, Mayilvanan C, Akilavalli N et al (2013) Effect of bisphenol-A on insulin signal transduction and glucose oxidation in skeletal muscle of adult male albino rat. Hum Exp Toxicol 32(9):960–971

    Article  CAS  PubMed  Google Scholar 

  35. Nova E, Redondo-Useros N, Martinez-Garcia RM, Gomez-Martinez S, Diaz-Prieto LE, Marcos A (2020) Potential of Moringa oleifera to improve glucose control for the prevention of diabetes and related metabolic alterations: a systematic review of animal and human studies. Nutrients 12(7)

  36. Meng X, Tang GY, Liu PH, Zhao CJ, Liu Q, Li HB (2020) Antioxidant activity and hepatoprotective effect of 10 medicinal herbs on CCl4-induced liver injury in mice. World J Gastroenterol 26(37):5629–5645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bukowska B (2004) Glutathione: its biosynthesis, induction agents and concentrations in selected diseases. Med Pr 55(6):501–509

    CAS  PubMed  Google Scholar 

  38. Gueraud F, Atalay M, Bresgen N, Cipak A, Eckl PM, Huc L et al (2010) Chemistry and biochemistry of lipid peroxidation products. Free Radic Res 44(10):1098–1124

    Article  CAS  PubMed  Google Scholar 

  39. Akinlolu AA, Oyewopo AO, Kadir RE, Lawal A, Ademiloye J, Jubril A et al (2021) Moringa oleifera and Musa sapientum ameliorated 7,12-Dimethylbenz [a]anthracene-induced upregulations of Ki67 and multidrug resistance 1 genes in rats. Int J Health Sci (Qassim) 15(3):26–33

    CAS  Google Scholar 

  40. Wang K, Zhao Z, Ji W (2019) Bisphenol A induces apoptosis, oxidative stress and inflammatory response in colon and liver of mice in a mitochondria-dependent manner. Biomed Pharmacother 117:109182

    Article  CAS  PubMed  Google Scholar 

  41. Savastano S, Tarantino G, D'Esposito V, Passaretti F, Cabaro S, Liotti A et al (2015) Bisphenol-A plasma levels are related to inflammatory markers, visceral obesity and insulin-resistance: a cross-sectional study on adult male population. J Transl Med 13:169

    Article  PubMed  PubMed Central  Google Scholar 

  42. Heinrichs D, Brandt EF, Fischer P, Kohncke J, Wirtz TH, Guldiken N et al (2021) Unexpected pro-fibrotic effect of MIF in non-alcoholic steatohepatitis is linked to a shift in NKT cell populations. Cells 10(2)

  43. Kimura K, Nagaki M, Nishihira J, Satake S, Kuwata K, Moriwaki H (2006) Role of macrophage migration inhibitory factor in hepatitis B virus-specific cytotoxic-T-lymphocyte-induced liver injury. Clin Vaccine Immunol 13(3):415–419

    Article  PubMed  PubMed Central  Google Scholar 

  44. Xie J, Yang L, Tian L, Li W, Yang L, Li L (2016) Macrophage migration inhibitor factor upregulates MCP-1 expression in an autocrine manner in hepatocytes during acute mouse liver injury. Sci Rep 6:27665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Muangnoi C, Chingsuwanrote P, Praengamthanachoti P, Svasti S, Tuntipopipat S (2012) Moringa oleifera pod inhibits inflammatory mediator production by lipopolysaccharide-stimulated RAW 264.7 murine macrophage cell lines. Inflammation 35(2):445–455

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to express deep appreciation and thanks to the Central Laboratory Unit, Faculty of Medicine, Menoufia University, for providing us with the necessary instruments for the completion of the study.

Funding

There has been no financial support for this work that could have influenced its outcome.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Kom, Egypt

    Yasmin A. Abd-Elnaby, Ibrahim E. ElSayed & Mona M. Abdelhafez

  2. Department of Biochemistry, Faculty of Veterinary Medicine, Menoufia University, Shebin El Kom, Egypt

    Mabrouk A. AbdEldaim

  3. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt

    Eman A. Badr & Ibrahim Elmadbouh

Authors
  1. Yasmin A. Abd-Elnaby
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  5. Mona M. Abdelhafez
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  6. Ibrahim Elmadbouh
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Contributions

YAA, IEE, MAA, EAB, MMA, and IE contributed to the study concept, design, clinical investigations, methodology, data collection, statistical analysis, and interpretation of the data. IEE, MAA, EAB, and IE contributed to the supervision and conceptualization in the study. All authors contributed to the writing of the papers and critically revised and finalized the paper. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Ibrahim Elmadbouh.

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Ethics approval and consent to participate

This study was done on an animal model after approval of the Ethics Committee of the Faculty of Medicine, Menoufia University. The committee’s reference number is IRB 4/2021PEDI2. The study was conducted in accordance with the Helsinki Declaration of 1964, as revised in 2013.

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Not applicable.

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The authors declare that they have no competing interests.

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Abd-Elnaby, Y.A., ElSayed, I.E., AbdEldaim, M.A. et al. Anti-inflammatory and antioxidant effect of Moringa oleifera against bisphenol-A-induced hepatotoxicity. Egypt Liver Journal 12, 57 (2022). https://doi.org/10.1186/s43066-022-00219-7

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