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Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats

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Abstract

Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [3H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H2O2 (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.

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Abbreviations

Fe-NTA:

Ferric nitrilotriacetate

MPO:

Myloperoxidase

BUN:

Blood urea nitrogen

ROS:

Reactive oxygen species

GSH:

Reduced glutathione

GST:

Glutathione-S-transferase

DTNB-50:

Dithio-bis 2-nitrobenzoic acid

CDNB:

1-Chloro 2,4-dinitrobenzene

NO:

Nitric oxide

GR:

Glutathione reductase

GSSG:

Oxidized glutathione

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

EDTA:

Ethylenediamine tetra acetic acid

LDH:

Lactate dehydrogenase

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Acknowledgments

The authors are thankful to Centre of Council for Research in Unani Medicine (CCRUM), Department of AYUSH, Ministry of Health and Family Welfare, Govt. of India, for providing the funds to carry out this study.

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Authors and Affiliations

  1. Molecular Carcinogenesis and Chemoprevention Division, Department of Medical Elementology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Muneeb U. Rehman & Sarwat Sultana

  2. Molecular Carcinogenesis and Chemoprevention Division, Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Muneeb U. Rehman & Sarwat Sultana

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  1. Muneeb U. Rehman
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Correspondence to Sarwat Sultana.

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U. Rehman, M., Sultana, S. Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats. Mol Cell Biochem 357, 115–124 (2011). https://doi.org/10.1007/s11010-011-0881-7

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