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The interrelationship between gasotransmitters and lead-induced renal toxicity in rats.
Toxicol Lett. 2019 Aug; 310:39-50.TL

Abstract

This study explored the role of gasotransmitters in lead-induced nephrotoxicity. Long-term exposure of rats to lead resulted in its accumulation in kidney. The accumulated metal impaired kidney function and structure. Lead intoxication resulted in oxidative stress, inflammation and apoptosis in kidney. In addition, it resulted in nitric oxide (NO) overproduction and decrease in hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in kidney. Inhibition of NO overproduction by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and CO level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of kidney function and structure. These agents inhibited lead-intoxication induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of H2S level and HO-1 concentration. Also, concomitant treatment with these agents inhibited lead intoxication-induced increase in protein expressions of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine- γ-lyase (CSE) in kidney. The NO donor, L-arginine and the H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively produced opposite effects and aggravated the toxic effects of lead. These results demonstrate, for the first time, that gasotransmitters play an important role in lead-induced nephrotoxicity.

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Authors+Show Affiliations

Abdel-Zaher AO
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. Electronic address: ahmedosmanaz@hotmail.com.
Abd-Ellatief RB
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Aboulhagag NA
Department of Patholology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Farghaly HSM
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Al-Wasei FMM
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.

MeSH

AnimalsApoptosisCarbon MonoxideCaspase 3CytokinesGasotransmittersHeme Oxygenase (Decyclizing)Hydrogen SulfideInflammation MediatorsKidneyKidney DiseasesMaleNitric OxideNitrosative StressOrganometallic CompoundsOxidative StressRats, WistarSignal Transduction

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30980911

Citation

Abdel-Zaher, Ahmed O., et al. "The Interrelationship Between Gasotransmitters and Lead-induced Renal Toxicity in Rats." Toxicology Letters, vol. 310, 2019, pp. 39-50.
Abdel-Zaher AO, Abd-Ellatief RB, Aboulhagag NA, et al. The interrelationship between gasotransmitters and lead-induced renal toxicity in rats. Toxicol Lett. 2019;310:39-50.
Abdel-Zaher, A. O., Abd-Ellatief, R. B., Aboulhagag, N. A., Farghaly, H. S. M., & Al-Wasei, F. M. M. (2019). The interrelationship between gasotransmitters and lead-induced renal toxicity in rats. Toxicology Letters, 310, 39-50. https://doi.org/10.1016/j.toxlet.2019.04.012
Abdel-Zaher AO, et al. The Interrelationship Between Gasotransmitters and Lead-induced Renal Toxicity in Rats. Toxicol Lett. 2019;310:39-50. PubMed PMID: 30980911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The interrelationship between gasotransmitters and lead-induced renal toxicity in rats. AU - Abdel-Zaher,Ahmed O, AU - Abd-Ellatief,Rasha B, AU - Aboulhagag,Noha A, AU - Farghaly,Hanan S M, AU - Al-Wasei,Fahmy M M, Y1 - 2019/04/11/ PY - 2018/11/13/received PY - 2019/03/06/revised PY - 2019/04/08/accepted PY - 2019/4/14/pubmed PY - 2019/5/29/medline PY - 2019/4/14/entrez KW - Apoptosis KW - Gasotransmitters KW - Inflammation KW - Lead KW - Nephrotoxicity KW - Oxidative stress SP - 39 EP - 50 JF - Toxicology letters JO - Toxicol Lett VL - 310 N2 - This study explored the role of gasotransmitters in lead-induced nephrotoxicity. Long-term exposure of rats to lead resulted in its accumulation in kidney. The accumulated metal impaired kidney function and structure. Lead intoxication resulted in oxidative stress, inflammation and apoptosis in kidney. In addition, it resulted in nitric oxide (NO) overproduction and decrease in hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in kidney. Inhibition of NO overproduction by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and CO level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of kidney function and structure. These agents inhibited lead-intoxication induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of H2S level and HO-1 concentration. Also, concomitant treatment with these agents inhibited lead intoxication-induced increase in protein expressions of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine- γ-lyase (CSE) in kidney. The NO donor, L-arginine and the H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively produced opposite effects and aggravated the toxic effects of lead. These results demonstrate, for the first time, that gasotransmitters play an important role in lead-induced nephrotoxicity. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/30980911/The_interrelationship_between_gasotransmitters_and_lead_induced_renal_toxicity_in_rats_ DB - PRIME DP - Unbound Medicine ER -
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