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Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity

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Abstract

Aluminum has toxic potential on humans and animals when it accumulates in various tissues. It was shown in a number of studies that aluminum causes oxidative stress by free radical formation and lipid peroxidation in tissues and thus may cause damage in target organs. Although there are numerous studies investigating aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have yet to be explained. Melatonin produced by pineal gland was shown to be an effective antioxidant. Since kidneys are target organs for aluminum accumulation and toxicity, we have studied the role of melatonin against aluminum-induced renal toxicity in rats. Wistar albino rats were divided into five groups. Group I served as control, and received only physiological saline; group II served as positive control for melatonin, and received ethanol and physiological saline; group III received melatonin (10 mg/kg); group IV received aluminum sulfate (5 mg/kg) and group V received aluminum sulfate and melatonin (in the same dose), injected three times a week for 1 month. Administration of aluminum caused degenerative changes in renal tissues, such as increase in metallothionein immunoreactivity and decrease in cell proliferation. Moreover, uric acid and lipid peroxidation levels and xanthine oxidase activity increased, while glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate dehydrogenase, and sodium potassium ATPase activities decreased. Administration of melatonin mostly prevented these symptoms. Results showed that melatonin is a potential beneficial agent for reducing damage in aluminum-induced renal toxicity.

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Abbreviations

AEC:

3-Amino-9-ethylcarbazole

Al:

Aluminum

Al2(SO4)3 :

Aluminum sulfate

AOS:

Antioxidant defense system

CAT:

Catalase

DETAE:

Experimental Medical Research Institute of Istanbul University

G6PD:

Glucose-6-phosphate dehydrogenase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Glutathione

GST:

Glutathione-S-transferase

HMS:

Pentose phosphate pathway

Ki-67:

Nuclear antigen that detects cells in synthesis phase

LPO:

Lipid peroxidation

Mel:

Melatonin

MT:

Metallothionein

Na+/K+-ATPase:

Sodium/potassium ATPase

PBS:

Phosphate buffer

PC:

Protein carbonyl

PON1:

Paraoxonase 1

ROS:

Reactive oxygen species

SD:

Standard deviation

SE:

Standard error

SOD:

Superoxide dismutase

XO:

Xanthine oxidase

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Acknowledgments

This study was supported by Scientific Research Projects Coordination Unit of Istanbul University (Project No: 4729 and UDP -33257).

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Turkey

    Omur Karabulut-Bulan, Pelin Arda-Pirincci, Guner Sarikaya-Unal & Huseyin Us

  2. Department of Chemistry, Faculty of Engineering, Istanbul University, 34320, Avcilar, Istanbul, Turkey

    Bertan Boran Bayrak & Refiye Yanardag

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  1. Omur Karabulut-Bulan
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Correspondence to Omur Karabulut-Bulan.

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Karabulut-Bulan, O., Bayrak, B.B., Arda-Pirincci, P. et al. Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity. Biol Trace Elem Res 168, 141–149 (2015). https://doi.org/10.1007/s12011-015-0320-9

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