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Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity

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Abstract

Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity.

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Abbreviations

CAT:

Catalase

DNPH:

2,4-Dinitrophenyl hydrazine

DTT:

Dithiothreitol

γGC:

γ-Glutamyl cysteine

GPx:

Glutathione peroxidase

GSH:

Reduced glutathione

H&E:

Hematoxylin and eosin

IL-1β:

Interleukin-1-β

IL-6:

Interleukin-6

MDA:

Malondialdehyde

PBS:

Phosphate-buffered saline

PCC:

Protein carbonyl content

PCNA:

Proliferating cell nuclear antigen

PMSF:

Phenylmethanesulfonyl fluoride

ROS:

Reactive oxygen species

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

SOD:

Superoxide dismutase

TAC:

Total antioxidant capacity

TBARS:

Thiobarbituric acid reactive substance

TCA:

Trichloroacetic acid

TNF-α:

Tumor necrosis factor-α

TMB:

3,3′,5,5′-Tetramethylbenzidine

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Acknowledgments

We greatly thank Prof. Adel Kholoussy (Professor of Pathology, Cairo University, Egypt) for his contribution in the histopathological examination.

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Correspondence to Samir A. Salama.

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All procedures related to animal care, treatments, and sampling were conducted according to the guidelines of Taif University research ethical committee.

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The authors declare that they have no competing interests.

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Salama, S.A., Arab, H.H., Maghrabi, I.A. et al. Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity. Biol Trace Elem Res 173, 96–107 (2016). https://doi.org/10.1007/s12011-016-0624-4

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