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. 2024 Sep 2;13(5):tfae141. doi: 10.1093/toxres/tfae141

Boosting impacts of Acacia nilotica against hepatic toxicity induced by gentamicin: biochemical, anti-inflammatory and immunohistochemical study

Saed A Althobaiti 1,✉
PMCID: PMC11368662  PMID: 39233845

Abstract

It seems that gentamicin's toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN's extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100 mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.

Keywords: Gentamicin, Liver toxicity, Acacia Nilotica, Hepatic markers, Inflammatory markers

Introduction

For the most serious infections, doctors will prescribe gentamicin (GM), an aminoglycoside antibiotic that is commonly used. Reports suggested that receiving gentamycin, patients may develop liver and renal impairments.1 A large body of research showing that gentamicin causes toxicity through numerous pathways, including the activation of inflammatory processes and the lowering of liver activity.2 These pathways culminate in cellular destruction, fibrosis, and congestion in the liver. In gentamicin-induced liver toxicity there was upregulation in tumor necrosis factor alpha secretion and expression.3 It has been demonstrated that antioxidants and anti-inflammatory biomarkers can reduce or even reverse the renal damage caused by gentamicin.3 Peoples have turned to herbal medicines to help with a variety of health issues. The Acacia genus has around 1,300 species, which are abundant in the tropics and the warmest latitudes.4  A. nilotica, a tree in the family Fabaceae, is used medicinally for a variety of ailments, such as the common cold, dysentery, diarrhea, biliousness, leukoderma, and common bronchitis.5 Some types of skin, mouth, and bones are targets for their use by traditional healers. Ear, ocular, and testicular malignancies can be treated using the gum and/or bark. The wood is used to treat tuberculosis, the leaves to treat smallpox, and the root to treat ulcers.6 Multiple biological activities have been associated with A. nilotica, including antispasmodic and anti-hypertensive effects,7 antidiabetic,8 hypocholesterolemic,9 and lowered diabetes-related liver failure risk.10

The present investigation was planned to examine the efficacy of Acacia nilotica (AN) extract in protecting rats' liver from gentamicin-induced liver toxicity.

Materials and methods

Animals

We used 28 male Wister rats, weighing between 150 and 155 grams. The animals were cared after and given complimentary meals. All procedures used in these experiments were in accordance with those established by our university, Saudi Arabia, and the National Institutes of Health. Fifteen days before the start of the tests, the animals were handled.

Animal experiments

The rats were divided into four groups at random once they were received. The first group of rats was given normal saline as control for fifteen days. The second group received 5% Acacia Nilotica extract. The third group had fifteen consecutive days of intraperitoneal gentamicin at a dose of 100 mg/kg. The protective group received an intraperitoneal injection of 100 mg/kg of gentamicin and 5% AN extract for a period of fifteen days. Both the control and gentamycin-treated rats received the same volume of normal saline.

Sampling

Following euthanasia, rats were subjected to decapitation after fifteen days. We collected blood from the venous plexuses around the eyes and nose. Once the coagulation process was complete, the blood was spun at 1,000 ×g for 15 min to extract the serum. The serum was then stored at −30 °C for use in further chemical analyses. After removing liver from each rat, it was homogenized in cold PBS. The next step was to vortex the homogenate for 8 min at 2,000 × p °C. We stored the supernatant at −20 °C. Some parts of renal tissues were embedded in formalin (10%) for immunohistochemistry and histological studies.

Liver biomarkers and inflammatory cytokines measurements

Kits were used to measure serum alanine aminotransferase (ALT), total bilirubin, gamma gutamyl transferase (GGT), and aspartate aminotransferase (AST), all were assessed following the protocols provided with each kit and were purchased from Biodiagnostic company, Giza (Egypt). IL1β, IL-6, and TNF-α serum levels were measure as described in the instruction manual of each supplied kit, as previously described.11

Histological and immunohistopathological findings

Liver samples were submerged in a 10% neutral formaldehyde buffer solution (Sigma-Aldrich) for a duration of one day. As stated by Bancroft and Layton,12 a paraffin integration device was used to fix the tissues.. Immunohistological examinations of the liver were down as described elsewhere.13 The liver tissues were immersed in paraffin wax after drying. The liver was sectioned into five small pieces, mounted, and left to incubate for 12 h. After being blocked for 30 min, the sections were incubated at 4 ° C for 12 h with diluted polyclonal anti-TGF-β, NF-kB, and COX-2 antibodies (1:2000). After three washing in PBS, the sections were incubated with the second antibody, which is a biotinylated anti-rabbit IgG at a concentration of 1:500. Lastly, the samples were left to incubate at room temperature for 30 min with avidin-biotin-peroxidase. Hematoxylin was used as a counterstain for the samples. To see the peroxidase response, DAB was used.

Statistical analysis

Data is expressed as means ± SEM. The data was analyzed using GraphPad Prism 5 program. One-way ANOVA was used to analyze current data. Tukey–Kramer post-analysis test was used to examine the means. The significance level was established at P < 0.05.

Results

Ameliorative effects of A. nilotica (AN) against gentamicin induced changes on biochemical and inflammatory cytokines markers

Our results revealed that there were significant increases in hepatic biomarkers (ALT, AST, GGT and total bilirubin) in gentamycin-injected rats compared to other groups. AN co-administration with gentamycin-injected rats showed significant normalization in elevated liver biomarkers as shown in Fig. 1. In the same context, gentamycin administration induced an increase in proinflammatory cytokines that were represented by increase in serum levels of IL-1 beta, IL-6, and TNF-alpha. All were ameliorated by co-administration of AN with gentamycin as seen in Fig. 2.

Fig. 1.

Fig. 1

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The effect of Acacia nilotica supplementation on the level of ALT, AST, Total bilirubin, and serum GGT of different groups. Values are represented as mean ± SEM. Columns with different letters means values with different letters superscripts were significantly different P < 0.05.

Fig. 2.

Fig. 2

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Effect of Acacia nilotica supplementation on the level of IL-1b, serum TNF-a, and IL-6 of different groups. Values are represented as mean ± SEM. Columns with different letters means values with different letters superscripts were significantly different P < 0.05.

Ameliorative role of A. nilotica (AN) treatment on renal histopathology

Data presented in Fig. 3 show that the control and AN treated group, showed normal architecture of portal area with polyhedral shaped hepatocytes arranged in cord-like and separated by blood sinusoids contained Kupffer cells in addition to intact portal vein. The gentamicin-treated rats showed severe congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area, hypertrophy of bile duct hepatocellular necrosis and infiltration of inflammatory cells. In protective group (gentamycin plus AN receiving rats), showed ameliorative effect for AN against gentamycin as there was a moderate congestion of hepatic sinusoids and small areas of vacuolar degenerative changes in hepatocytes.

Fig. 3.

Fig. 3

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Photomicrograph of liver of control group a) and AN B) showing normal architecture of portal area with polyhedral shaped hepatocytes arranged in cord-like pattern (white arrow heads) and separated by blood sinusoids (black arrow heads) contained Kupffer cells (thin arrows) in addition to intact portal vein (thick arrow) Stain H&E, bar = 50 μm. Photomicrograph of liver of gentamicin treated group C) showing severe congestion of portal vein (thick black arrow), and hepatic sinusoids (black arrow heads) besides fibrosis of portal area (white arrows), hypertrophy of bile duct (white arrow heads) hepatocellular necrosis (asterisk) and infiltration of inflammatory cells (thin black arrow). Stain H&E, bar = 50 μm. Photomicrograph of liver of gentamicin plus AN treated group D) showing moderate congestion of hepatic sinusoids (arrow heads) and small areas of vacuolar degenerative changes in hepatocytes (arrows). Stain H&E, bar = 50 μm.

Ameliorative impact of A. nilotica (AN) treatment on immunohistochemistry and immunoreactivity COX-2, NF-kB, and TGF-β1 in liver

Figure 4 showed COX-2 immunoreactivity was negative in the control and AN administered rats. Gentamycin administered rats showed strong positive immunoreactivity that were ameliorated when AN co-administered for gentamycin rats. In the same context, inflammatory transcriptional fact known NFkB showed negative staining in control and AN received rats. NFkB showed positive and strong immunoreactivity in hepatocytes in the peri-portall area in gentamycin administered rats (Fig. 5).

Fig. 4.

Fig. 4

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Photomicrograph of liver of the control group (A) and AN group (B) showing negative immunoreactivity of COX-2 in hepatocytes. In C, the photomicrograph of liver in gentamicin injected rats showing significant increase of COX2 positive hepatocytes (arrows). In D, the photomicrograph of liver of the gentamicin + AN treated group showed a marked decrease in COX2-positive brown stains (arrows). COX-2 IHC, bar = 50 μm.

Fig. 5.

Fig. 5

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Photomicrograph of liver of the control group (A) and AN group (B) showing negative immunoreactivity of NFkB in hepatocytes. In C, the photomicrograph of liver in gentamicin injected rats showing significant increase of NFkB positive reactivity of hepatocytes and in peri-portal vein (arrows and brown stains). NFkB IHC, bar = 50 μm. In D, the photomicrograph of liver of the gentamicin + AN treated group showed a marked decrease in NFkB -positive brown stains as indicated by arrows. NFkB IHC, bar = 50 μm.

Finally, the expression of transforming growth factor-beta-1 (TGF-β1) was very faint in control and AN administered rats. The immunoreactivity was strong in gentamycin intoxicated rats and was significantly decreased when AN was co-administered to gentamycin receiving rats (Fig. 6).

Fig. 6.

Fig. 6

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Photomicrograph of the liver of the control group a) and AN B) groups showing negative expression of TGF-β. photomicrograph of liver of gentamicin treated group C) showing a significant increase of TGF-β1 with positive staining in hepatocytes and in the peri-portal area (arrows). Photomicrograph of liver in gentamicin + AN D) treated rats showing a marked decrease in TGF-β1 immunoreactivity (arrows). TGF-β1 IHC, bar = 50 μm.

Discussion

Gentamicin is the most effective antibiotic against germs that have developed resistance to other drugs, even though it can harm the kidneys. The hepatic and nephrotoxicity caused by gentamicin are the most common in experimental animals.14 By activating nuclear factor kappa B, reactive oxygen species substantially facilitate the initiation of the inflammatory process.15 A possible explanation for the pathophysiology of gentamicin-induced liver toxicity is the interplay between oxidative stress, inflammation of organs, and feedback loops that increase damage and connect the processes that cause changes in tubules and glomeruli.15 An increase in blood liver enzymes and the development of histological lesions are indicators that GEN has hepatotoxic effects. Major factors in the pathogenesis of GEN-induced liver damage include inflammation and oxidative stress.16,17

The association between liver toxicity induced by gentamycin and ALT, GGT, AST, IL-6, and IL-1β and TNF-alpha parameters were validated in this study. Results from the histological examination of the gentamycin group demonstrated hepatocyte necrosis, and congestion of the portal vein. The results showed that in the protected group, showed some amelioration compared to intoxicated rats. Finally, in all treated groups, the immune-expression of the COX-2, NFKB and TGF-β1 were decreased.

Increased levels of liver biomarkers demonstrated by GEN-injected mice demonstrated liver damage, as seen in the present study (Fig. 1). Other researchers have found comparable outcomes.18 Inflammation and alterations in the structure of the liver cause an elevation of enzymes in the liver.19 Rats given AN and GEN demonstrated a marked reduction in hepatic enzyme levels; this leads us to believe that AN prevented GEN-induced liver damage by blocking the leakage of liver enzymes. It has been found that AN had a hepato-protective effect against hepatic tissue damage, confirming the ameliorative effect of AN during organs stress.20  Acacia nilotica's ability to modulate the immune system and reduce inflammation is based on its ability to regulate the activation of several inflammatory mediators and biomarkers.21

NFkB is just one of many transcriptional factors that have been associated to different types of inflammation.22 It controls how inflammatory mediators named cytokines and chemokines are expressed in the body.23 Nuclear factor kB (NFkB) stimulates transcription of pro-inflammatory genes and the inflammatory response upon DNA binding.24 Therefore, reducing inflammation may be possible through inhibition of the NFkB pathway25 as oxidative stress signals arising from ROS increase NFkB expression.26 TNF-α is the cause for the increase in IL-1β and interferon-γ production.27 In this study, gentamycin injection elevated TNF-α and IL-1β and IL-6 significantly,28 increased levels of NFkB and TNF-α messenger RNAs in liver tissues.29

According to Brasier30 oxidative stress has the ability to activate NFkB, a protein that is crucial for inflammatory responses, cell proliferation, and programmed cell death. This study found that the experimental animals' kidneys showed an elevation of NFkB immune-reactivity, suggesting that gentamicin therapy boosted NF-κB. Injuries were linked to an increase in COX-2 and TGF-β1 expression.31 It was found that the action of gentamycin on inflammatory cytokines might be counteracted by co-treatment of AN with gentamycin. It has been reported that A. nilotica reduced cyclooxygenase-2 (COX-2) stimulation in rats treated with CCl4, which was in line with our results. The biological activities of the AN, including its anti-inflammatory properties derived from its phenolic components, were responsible for this effects.32

Conclusions

Acacia Nilotica extraction ameliorated hepatic toxicity induced by the gentamycin administration through its role as anti-inflammatory mediator activity through modulation of the COX-2, NF-kB, and TGF-β1 activities. It regulated the levels of inflammatory cytokines such as IL-1β, IL-6 and TNF-α. It restored the altered histopathological changes induced by gentamycin. Therefore, using Acacia Nilotica as a supplement against hepatic toxicity is strongly suggested.

Acknowledgments

The authors extend their appreciation to Taif University, Saudi Arabia, for supporting this work through project number (TU-DSPP-2024-260).

Author contribution

Saed Althobaiti has designed, analyzed, wrote and submitted this study.

Funding

This research was funded by Taif University, Saudi Arabia, Project No. (TU-DSPP-2024-260).

 

Conflict of interest statement. The authors have no conflict of interest.

Data availability

Upon request, the data used in this paper can be provided.

Ethical statement

All procedures pertaining to the use of animals in this study adhered to the standards set out by the National Institutes of Health.

References

  • 1. Ali  BH. Gentamicin nephrotoxicity in humans and animals: some recent research. Gen Pharmacol. 1995:26(7):1477–1487. [DOI] [PubMed] [Google Scholar]
  • 2. Al-Johani  AM, Al-Sowayan  NS. Protective effect of ethanolic extract of Elettaria Cardamomum against gentamicin hepato-renal toxicity in male albino rats. Eur Rev Med Pharmacol Sci. 2023:27(11):4828–4841. [DOI] [PubMed] [Google Scholar]
  • 3. Abdeen  A, Samir  A, Elkomy  A, Aboubaker  M, Habotta  OA, Alsanie  AGWF, Abdullah  O, Elnoury  HA, Baioumy  B, Ibrahim  SF, et al.  The potential antioxidant bioactivity of date palm fruit against gentamicin-mediated hepato-renal injury in male albino rats. Biomed Pharmacother. 2021:143:112154. [DOI] [PubMed] [Google Scholar]
  • 4. Seigler  DS. Phytochemistry of Acacia—sensu lato. Biochem Syst Ecol. 2003:31(8):845–873. [Google Scholar]
  • 5. Singh  B, Sharma  S, Dhiman  A. Acacia gum polysaccharide based hydrogel wound dressings: synthesis, characterization, drug delivery and biomedical properties. Carbohydr Polym. 2017:165:294–303. [DOI] [PubMed] [Google Scholar]
  • 6. Kalaivani  T, Mathew  L. Free radical scavenging activity from leaves of Acacia nilotica (L.) wild. Ex Delile, an Indian medicinal tree. Food Chem Toxicol. 2010:48(1):298–305. [DOI] [PubMed] [Google Scholar]
  • 7. Mani  JS, Johnson  JB, Hosking  H, Ashwath  N, Walsh  KB, Neilsen  PM, Broszczak  DA, Naiker  M. Antioxidative and therapeutic potential of selected Australian plants: a review. J Ethnopharmacol. 2021:268:113580. [DOI] [PubMed] [Google Scholar]
  • 8. Ansari  P, Islam  SS, Akther  S, Khan  JT, Shihab  JA, Abdel-Wahab  YHA. Insulin secretory actions of ethanolic extract of Acacia arabica bark in high fat-fed diet-induced obese type 2 diabetic rats. Biosci Rep. 2023:43(5):BSR20230329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Maciejewski  R, Ruciński  P, Burski  K, Figura  T. Changes in glucose, cholesterol and serum lipid fraction levels in experimental diabetes. Ann Univ Mariae Curie Sklodowska Med. 2001;56:363–368. [PubMed] [Google Scholar]
  • 10. Ahmad  M, Zaman  F, Sharif  T, Ch  MZ. Antidiabetic and hypolipidemic effects of aqueous methanolic extract of Acacia nilotica pods in alloxan-induced diabetic rabbits. Scand J Lab Anim Sci. 2008:35(1):29–34. [Google Scholar]
  • 11. Soliman  MM, Attia  HF, El-Ella  GA. Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: protection by sesame oil. Int J Immunopathol Pharmacol. 2015:28(4):508–520. [DOI] [PubMed] [Google Scholar]
  • 12. Bancroft  JD, Layton  C. The hematoxylins and eosin. In: Suvarna SK, Layton C, Bancroft JD, Editors. Bancroft’s theory and practice of histological techniques (Eighth Edition). Elsevier; 2012. pp. 173–186.
  • 13. Malkiewicz  K, Koteras  M, Folkesson  R, Brzezinski  J, Winblad  B, Szutowski  M, Benedikz  E. Cypermethrin alters glial fibrillary acidic protein levels in the rat brain. Environ Toxicol Pharmacol. 2006:21(1):51–55. [DOI] [PubMed] [Google Scholar]
  • 14. Farombi  E, Ekor  M. Curcumin attenuates gentamicin-induced renal oxidative damage in rats. Food Chem Toxicol. 2006:44(9):1443–1448. [DOI] [PubMed] [Google Scholar]
  • 15. Lopez-Novoa  JM, Quiros  Y, Vicente  L, Morales  AI, Lopez-Hernandez  FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2011:79(1):33–45. [DOI] [PubMed] [Google Scholar]
  • 16. Ali  FE, Hassanein  E, Bakr  A, el-Shoura  E, el-Gamal  D, Mahmoud  A, Abd-Elhamid  T. Ursodeoxycholic acid abrogates gentamicin-induced hepatotoxicity in rats: role of NF-κB-p65/TNF-α, Bax/Bcl-xl/Caspase-3, and eNOS/iNOS pathways. Life Sci. 2020:254:117760. [DOI] [PubMed] [Google Scholar]
  • 17. Arjinajarn  P, Chueakula  N, Pongchaidecha  A, Jaikumkao  K, Chatsudthipong  V, Mahatheeranont  S, Norkaew  O, Chattipakorn  N, Lungkaphin  A. Anthocyanin-rich Riceberry bran extract attenuates gentamicin-induced hepatotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Biomed Pharmacother. 2017:92:412–420. [DOI] [PubMed] [Google Scholar]
  • 18. Hegazy  A, Abdel-Azeem  AS, Zeidan  HM, Ibrahim  KS, Sayed  EME. Hypolipidemic and hepatoprotective activities of rosemary and thyme in gentamicin-treated rats. Hum Exp Toxicol. 2018:37(4):420–430. [DOI] [PubMed] [Google Scholar]
  • 19. Bakour  M, Soulo  N, Hammas  N, Fatemi  H, Aboulghazi  A, Taroq  A, Abdellaoui  A, Al-Waili  N, Lyoussi  B. The antioxidant content and protective effect of argan oil and Syzygium aromaticum essential oil in hydrogen peroxide-induced biochemical and histological changes. Int J Mol Sci. 2018:19(2):610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Ahmed  AA, Fedail  JS, Musa  HH, Kamboh  AA, Sifaldin  AZ, Musa  TH. Gum Arabic extracts protect against hepatic oxidative stress in alloxan induced diabetes in rats. Pathophysiology. 2015:22(4):189–194. [DOI] [PubMed] [Google Scholar]
  • 21. Feng  T, Zhang  M, Xu  Q, Song  F, Wang  L, Gai  S, Tang  H, Wang  S, Zhou  L, Li  H. Exploration of molecular targets and mechanisms of Chinese medicinal formula acacia catechu -Scutellariae radix in the treatment of COVID-19 by a systems pharmacology strategy. Phytother Res. 2022:36(11):4210–4229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Wang  R, Yu  XY, Guo  ZY, Wang  YJ, Wu  Y, Yuan  YF. Inhibitory effects of salvianolic acid B on CCl(4)-induced hepatic fibrosis through regulating NF-κB/IκBα signaling. J Ethnopharmacol. 2012:144(3):592–598. [DOI] [PubMed] [Google Scholar]
  • 23. Lawrence  T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009:1(6):a001651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Park  JS, Woo  MS, Kim  DH, Hyun  JW, Kim  WK, Lee  JC, Kim  HS. Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells. J Pharmacol Exp Ther. 2007:320(3):1237–1245. [DOI] [PubMed] [Google Scholar]
  • 25. Sun  P, Song  SZ, Jiang  S, Li  X, Yao  YL, Wu  YL, Lian  LH, Nan  JX. Salidroside regulates inflammatory response in raw 264.7 macrophages via TLR4/TAK1 and ameliorates inflammation in alcohol binge drinking-induced liver injury. Molecules. 2016:21(11):1490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Herpers  B, Wink  S, Fredriksson  L, di  Z, Hendriks  G, Vrieling  H, de Bont  H, van de Water  B. Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity. Arch Toxicol. 2016:90(5):1163–1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Oku  H, Nakazato  H, Horikawa  T, Tsuruta  Y, Suzuki  R. Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin-10 and protects mice from endotoxic shock. Eur J Pharmacol. 2002:446(1–3):167–176. [DOI] [PubMed] [Google Scholar]
  • 28. Sakthivel  KM, Guruvayoorappan  C. Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators-(TNF-a, iNOS, COX-2, IL-1β, IL-6, IFN-γ, IL-2, GM-CSF) and pro-angiogenic growth factor- VEGF. Asian Pac J Cancer Prev. 2013:14(6):3909–3919. [DOI] [PubMed] [Google Scholar]
  • 29. Hamid  M, Abdulrahim  Y, Liu  D, Qian  G, Khan  A, Huang  K. The Hepatoprotective effect of selenium-enriched yeast and gum Arabic combination on carbon tetrachloride-induced chronic liver injury in rats. J Food Sci. 2018:83(2):525–534. [DOI] [PubMed] [Google Scholar]
  • 30. Brasier  AR. The NF-κB regulatory network. Cardiovasc Toxicol. 2006:6(2):111–130. [DOI] [PubMed] [Google Scholar]
  • 31. Gao  X, Picchi  A, Zhang  C. Upregulation of TNF-alpha and receptors contribute to endothelial dysfunction in zucker diabetic rats. Am J Biomed Sci. 2010:2(1):1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Omara  EA, Nada  SA, El-Toumy  SA. Evaluation of hepatoprotective activity of the Acacia nilotica flowers on carbon tetrachloride-induced liver damage in rats. Planta Med. 2013:79(13):PB36. [Google Scholar]

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Data Availability Statement

Upon request, the data used in this paper can be provided.

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