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Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma–induced hepatorenal injury in mice

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Abstract

Ehrlich ascites carcinoma induces hepatorenal injuries while acridine derivatives have antioxidant, anticancer, and anti-inflammatory. Thus, this study evaluated the protective potential of a newly synthesized the 9-diaminoacridine derivative (9-DAAD), N1-(acridin-9-yl) propane-1, 3-diamine hydrochloride, against Ehrlich ascites carcinoma (EAC) induced hepatorenal injury in female mice. Forty female mice were allocated into 4 groups. Group I was injected with 0.1% DMSO subcutaneously and kept a control. Group II received 9-DAAD (30 mg/kg bw/2 days) subcutaneously for 2 weeks. Group III was injected interaperitonealy with 2.5 × 106 cells of EAC/20 g bw. Group IV was injected with EAC as the third group and administered with 9-DAAD as the second group for 2 weeks after induction of EAC. EAC significantly elevated total leukocytes and platelets counts; activities of serum AST, ALT, and ALP; serum levels of alpha-fetoprotein; carcinoembryonic antigen; urea and creatinine; and expression of vascular endothelial growth factor protein in hepatic and renal tissues. Meanwhile it decreased red blood cells count, hemoglobin concentration and hematocrit value. At the same time, it significantly reduced serum levels of total protein and albumin and altered hepatic and renal tissues structures. Also, EAC decreased apoptosis and DNA synthesis in hepatic and renal cells. However, treatment of EAC-bearing mice with 9-DAAD improved liver and kidney structures, functions and modulated EAC altered parameters, as well as it reduced hepatic and renal cells proliferation and DNA synthesis. This study indicated that 9-DAAD had a potential ameliorative effect against EAC-induced hepatorenal injury.

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Data availability

All data used in this study are included in this published article

Abbreviations

AFP:

Alpha-fetoprotein

Alb:

albumin

ALP:

Alkaline phosphatase

ALT:

Alanine transaminase

AST:

Aspertate transaminase

CBC:

Complete blood count

CEA:

Carcinoembryonic antigen

Cv:

Central vein

9-DAAD:

N1-(acridin-9-yl) propane-1, 3-diamine hydrochloride

EAC:

Ehrlich ascites carcinoma

EST:

Ehrlich solid tumor

G:

Glomeruli

H&E:

Hemotoxylin and eosin

Hb:

Hemoglobin

Hct:

Hematocrit

Hp:

Hepatocellular

MCHC:

Mean corpuscular hemoglobin concentration

MCV:

Mean corpuscular volume

Plt:

Platelets

RBCs:

Red blood cells

ROS:

Reactive oxygen species

Rt:

Renal tissue

T. Protein:

Total protein

VEGF:

Vascular endothelial growth factor

WBCs:

White blood cells

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Authors and Affiliations

  1. Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Sheben Elkom, Menoufia, 32511, Egypt

    Mabrouk Attia Abd Eldaim

  2. Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt

    Ehab Tousson

  3. Chemistry Department, Faculty of Science, Menoufia University, Sheben Elkom, 32511, Egypt

    Ibrahim El Tantawy El Sayed, Asmaa Zakaria Abd Elmaksoud & Abdullah A. S. Ahmed

Authors
  1. Mabrouk Attia Abd Eldaim
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  2. Ehab Tousson
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  3. Ibrahim El Tantawy El Sayed
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  4. Asmaa Zakaria Abd Elmaksoud
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  5. Abdullah A. S. Ahmed
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Contributions

Abd Eldaim MA and Tousson E suggested the idea and experimental design; Abd Elmaksoud, AZ and Ahmed A AS performed the experiment and wrote the draft of manuscript with the support of El Sayed IE and Tousson E; Abd Eldaim MA, Tousson E, and El Sayed IE supervised the implementation of the experiment and analyzed the results; Tousson E and Abd Elmaksoud AZ performed the histopathological examination. All authors discussed the results and contributed to finalize the manuscript.

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Correspondence to Mabrouk Attia Abd Eldaim.

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All authors declared that they have no conflicts of interest regarding the publication of this manuscript

Ethical approval

Rearing, treatment of mice and all the experimental procedures were conducted in accordance with guide for animal use and approved by animal care and use committee (IACUC-SCI-TU- 0067), Faculty of Science, Tanta university, which followed the National Institutes of Health Guide for Care and Use of Laboratory Animals (Publication No. 85-23, revised 1985).

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Responsible editor: Mohamed M. Abdel-Daim

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Highlights

• Ehrlich ascites carcinoma (EAC) altered liver and kidney functions and structures.

• EAC elevated protein expression of tumor and angiogenesis biomarkers.

• EAC decreased apoptosis and DNA synthesis in hepatic and renal cells.

• 9-Diaminoacridine (9-DAAD) improved liver and kidney structures and functions.

• 9-DAAD reduced hepatic and renal cells proliferation and DNA synthesis.

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Abd Eldaim, M.A., Tousson, E., El Sayed, I.E.T. et al. Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma–induced hepatorenal injury in mice. Environ Sci Pollut Res 28, 21835–21850 (2021). https://doi.org/10.1007/s11356-020-11857-y

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  • DOI: https://doi.org/10.1007/s11356-020-11857-y

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