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The Effect of Boric Acid and Borax on Oxidative Stress, Inflammation, ER Stress and Apoptosis in Cisplatin Toxication and Nephrotoxicity Developing as a Result of Toxication

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Abstract

The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group. At the end of the study, oxidative stress-related (GSH, MDA, PCO, GPx, 8-OHdG), inflammation-related (TNF-α, IL-1β, IL-18, MCP-1, ICAM, TGF-β), apoptosis-related (p53, caspase 1, 3, 8, 12, bcl-2, bcl-xL, NFkB), and ER stress-related (GRP78, ATF-6, PERK) basic parameters were analyzed in serum, erythrocyte, and kidney tissues. Kidney tissues were also examined by histopathological and immunohistochemical methods. Borax and boric acid at different doses decreased inflammation and oxidative stress caused by cisplatin toxicity and increased ER stress. As a result of the treatments applied to experimental animals, it was determined that boric acid and borax reduced apoptotic damage in kidney tissue, but the decrease was statistically significant only in 200 mg/kg boric acid-administered group. In the study, low anti-apoptotic effects of borate doses with the anti-inflammatory and antioxidant effect may be due to increased ER stress at the relevant doses. Further studies on the effects of boron compounds on ER stress and apoptotic mechanisms may clarify this issue. Thus, possible side effects or if there are new usage areas of borone compounds which have many usage areas in clinics can be detected.

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Abbrevations

AKU Afyon Kocatepe Unıversty

BA boric acid

BX borax

DEPC diethylprocarbonate

PBS phosphate buffer solution

ELISA enzyme-linked immunosorbent assay

RT-PCR reverse transcription-polymerase chain Reaction

TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling method

HE Hematoxylin-eosin

ANOVA one-way analysis of variance

GSH glutathione

SOD superoxide dismutase.

CAT catalase

GPx gulutation peroxidase

NO nitric oxide

MDA malondialdehyde

hb hemoglobin

PCO oxide protein carbonyl

8-OHdG 8-hydroxy-deoxyguanosine

TNF-α tumor necrosis factor alpha

IL-β interleukin 1-beta

IL-18 interleukin-18

TBA thiobarbituric acid

cDNA complementary DNA

BUN blood urea nitrogen

CREA creatinine

NFKB nuclear factor kappa B

IFN-γ interferon gamma

Bcl-2 B cell lymphoma 2

Bcl-xL B cell lymphoma-extra large or Bcl2-like 1 isoform 1

p53 Tumor protein p53

GRP78 glucose-regulated protein, 78

TGF-β transforming growth factor-β

ICAM-1 intercellular adhesion molecule-1

MCP-1 monocyte chemoattractant protein-1

VEGF vascular endothelial growth factor

Funding

We declare that this study was financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK SBAG project number:114S063), Turkey.

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Authors and Affiliations

  1. Department of Chemistry, Biochemistry Division, Faculty of Science and Arts, Afyon Kocatepe University, Afyonkarahisar, Turkey

    Ömer Hazman & Fadime Erkan Uysal

  2. Department of Pathology, Faculty of Veterinary, Afyon Kocatepe University, Afyonkarahisar, Turkey

    Mehmet Fatih Bozkurt

  3. Department of Biochemistry, Faculty of Veterinary, Afyon Kocatepe University, Afyonkarahisar, Turkey

    Abdurrahman Fatih Fidan

  4. Department of Biochemistry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey

    Sefa Çelik

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  1. Ömer Hazman
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  2. Mehmet Fatih Bozkurt
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  4. Fadime Erkan Uysal
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  5. Sefa Çelik
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Corresponding author

Correspondence to Ömer Hazman.

Ethics declarations

All interventions carried out on the animals during the study were made at Afyon Kocatepe University Experemental Animals Research and Application Center, in line with the rules announced by Afyon Kocatepe University, Local Experimental Animal Ethics Committee (ethics committee number/date: 380/26.09.2013).

Conflict of Interest

This study was presented at 8th and 9th National Veterinary Biochemistry and Clinical Biochemistry Congress. In addition, part of the data contained in this article will be presented as the thesis of graduate student Fadime Erkan Uysal (one of the authors of this article).

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Hazman, Ö., Bozkurt, M.F., Fidan, A.F. et al. The Effect of Boric Acid and Borax on Oxidative Stress, Inflammation, ER Stress and Apoptosis in Cisplatin Toxication and Nephrotoxicity Developing as a Result of Toxication. Inflammation 41, 1032–1048 (2018). https://doi.org/10.1007/s10753-018-0756-0

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