Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway

The present study analyzes the efficacy of N-acetyl cysteine (NAC) against diazinon (DZN)-induced nephrotoxicity in male Wistar rats. Rats were divided into five groups with six animals in each group: Group 1 (G1) was maintained in typical control circumstances and given saline once daily intragast...

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Main Authors: Eman M. Fath, Hatem H. Bakery, Ragab M. EL Shawarby, Mohamed E.S. Abosalem, Nesrine Ebrahim, Ahmed Medhat Hegazy, Samar S. Ibrahim
Format: Article
Language:English
Published: Assiut University 2023-09-01
Series:Journal of Advanced Veterinary Research
Subjects:
Online Access:https://advetresearch.com/index.php/AVR/article/view/1472
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author Eman M. Fath
Hatem H. Bakery
Ragab M. EL Shawarby
Mohamed E.S. Abosalem
Nesrine Ebrahim
Ahmed Medhat Hegazy
Samar S. Ibrahim
author_facet Eman M. Fath
Hatem H. Bakery
Ragab M. EL Shawarby
Mohamed E.S. Abosalem
Nesrine Ebrahim
Ahmed Medhat Hegazy
Samar S. Ibrahim
author_sort Eman M. Fath
collection DOAJ
description The present study analyzes the efficacy of N-acetyl cysteine (NAC) against diazinon (DZN)-induced nephrotoxicity in male Wistar rats. Rats were divided into five groups with six animals in each group: Group 1 (G1) was maintained in typical control circumstances and given saline once daily intragastric (IG) for 4 weeks; G2 was administered 0.1 mL olive oil IG for 4 weeks; G3 was administered IG NAC 150 mg/kg daily as an aqueous solution for 4 weeks; G4 was administered IG diazinon at a dose of 15 mg/kg daily for 4 weeks; and G5 was administered IG NAC daily one hour before diazinon at the same dose in G3 and G4 for 4 weeks. Sub-chronic exposure to DZN impairs the kidney structure and function, as evidenced by the histopathology, immunohistochemistry, and gene expression of NLRP3, NFκB, IKB, BCL2, BAX mRNA. Our findings showed that NAC reduces the renal dysfunctions induced by DZN by restoring urea and creatinine levels as well as oxidative indicators. Moreover, serum inflammatory markers (IL-1β and TNF-α) concentrations were ameliorated by NAC treatment. However, NAC has shown to play a beneficial role against nephrotoxicity by reversing the cytoarchitecture and downregulation of inflammatory (NLRP3, NFκB, IKB) and apoptotic (BAX) as well as upregulated BCL2 genes and proteins in kidney tissues, bringing them to near-normal levels. Moreover, IHC examination of renal tissue revealed the attenuation of expression of TNF-α. Therefore, NAC could be potentially used to protect the kidneys from pathological changes induced by DZN.
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spelling doaj.art-faf41e4c19e54261b10befcf11f3dc862023-10-18T14:07:54ZengAssiut UniversityJournal of Advanced Veterinary Research2090-62692090-62772023-09-01138Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling PathwayEman M. Fath0Hatem H. Bakery1Ragab M. EL Shawarby2Mohamed E.S. Abosalem3Nesrine Ebrahim4Ahmed Medhat Hegazy5Samar S. Ibrahim6Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.Department of Histology and Cell Biology Faculty of Medicine, Benha University, Benha 13511, Egypt.Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt. The present study analyzes the efficacy of N-acetyl cysteine (NAC) against diazinon (DZN)-induced nephrotoxicity in male Wistar rats. Rats were divided into five groups with six animals in each group: Group 1 (G1) was maintained in typical control circumstances and given saline once daily intragastric (IG) for 4 weeks; G2 was administered 0.1 mL olive oil IG for 4 weeks; G3 was administered IG NAC 150 mg/kg daily as an aqueous solution for 4 weeks; G4 was administered IG diazinon at a dose of 15 mg/kg daily for 4 weeks; and G5 was administered IG NAC daily one hour before diazinon at the same dose in G3 and G4 for 4 weeks. Sub-chronic exposure to DZN impairs the kidney structure and function, as evidenced by the histopathology, immunohistochemistry, and gene expression of NLRP3, NFκB, IKB, BCL2, BAX mRNA. Our findings showed that NAC reduces the renal dysfunctions induced by DZN by restoring urea and creatinine levels as well as oxidative indicators. Moreover, serum inflammatory markers (IL-1β and TNF-α) concentrations were ameliorated by NAC treatment. However, NAC has shown to play a beneficial role against nephrotoxicity by reversing the cytoarchitecture and downregulation of inflammatory (NLRP3, NFκB, IKB) and apoptotic (BAX) as well as upregulated BCL2 genes and proteins in kidney tissues, bringing them to near-normal levels. Moreover, IHC examination of renal tissue revealed the attenuation of expression of TNF-α. Therefore, NAC could be potentially used to protect the kidneys from pathological changes induced by DZN. https://advetresearch.com/index.php/AVR/article/view/1472 DiazinonN-acetyl cysteineNephrotoxicityNLRP3Oxidative stress
spellingShingle Eman M. Fath
Hatem H. Bakery
Ragab M. EL Shawarby
Mohamed E.S. Abosalem
Nesrine Ebrahim
Ahmed Medhat Hegazy
Samar S. Ibrahim
Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
Journal of Advanced Veterinary Research
Diazinon
N-acetyl cysteine
Nephrotoxicity
NLRP3
Oxidative stress
title Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
title_full Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
title_fullStr Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
title_full_unstemmed Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
title_short Nephroprotective Effect of N-Acetyl-L-Cysteine against Diazinon-induced Nephrotoxicity in Rats via IKβ, NFκB, NLRP3 Signaling Pathway
title_sort nephroprotective effect of n acetyl l cysteine against diazinon induced nephrotoxicity in rats via ikβ nfκb nlrp3 signaling pathway
topic Diazinon
N-acetyl cysteine
Nephrotoxicity
NLRP3
Oxidative stress
url https://advetresearch.com/index.php/AVR/article/view/1472
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