Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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ɴ-Acetylcysteine protects against diazinon-induced histopathological damage and apoptosis in renal tissue of rats

  • Gaiqin Dong (Department of Nephrology and Immunology, Children's Hospital of Soochow University) ;
  • Qingfeng Li (Department of Pediatrics, Affiliated Hospital of Yangzhou University) ;
  • Chun Yu (Department of Pediatrics, Affiliated Hospital of Yangzhou University) ;
  • Qing Wang (Department of Pediatrics, Affiliated Hospital of Yangzhou University) ;
  • Danhua Zuo (Department of Pediatrics, Affiliated Hospital of Yangzhou University) ;
  • Xiaozhong Li (Department of Nephrology and Immunology, Children's Hospital of Soochow University)
  • Received : 2023.08.29
  • Accepted : 2024.01.22
  • Published : 2024.04.15
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Abstract

Diazinon (DZN) is a member of organophosphorus insecticides that has cytotoxic effects on different organs. ɴ-Acetyl cysteine (NAC) is a widely used antioxidant in clinical, in vivo and in vitro studies. We evaluated the protective role of NAC against DZN-induced toxicity in kidney tissue of Wistar rats. 30 male Wistar rats were divided into 5 groups of control, single dose of DZN, continuous dose of DZN, single doses of DZN + NAC and continuous doses of DZN + NAC. Kidney function test (blood urea nitrogen, creatinine and uric acid) was provided. Levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and total sulfhydryl (T-SH) were determined in renal tissues. Renal cells apoptosis was detected using TUNEL assay. The mRNA expressions of apoptosis, oxidative stress and inflammatory mediators, including B-cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (Bax), superoxide dismutase (SOD), catalase (CAT), Interleukin 10 (IL-10), Tumor necrosis factor-α (TNF-α), Caspase-3 and Caspase-8 were analyzed in kidney tissues using Real Time PCR method. Chronic exposure to DZN was associated with severe morphological changes in the kidney, as well as impairment of its function and decreased kidney weights. Continues treatment with DZN significantly decreased the percentage of renal apoptotic cells as compared to rats treated with continuous dose of DZN alone (17.69 ± 3.67% vs. 39.46% ± 2.44%; p < 0.001). Continuous exposure to DZN significantly decreased TAC and T-SH contents, as well as SOD and CAT expression, but increased MDA contents in the kidney tissues (p < 0.001). A significant increase was observed in mRNA expression of Bax, Caspase-3, Caspase-8, as well as TNF-α following exposure to DZN, but the expression of IL-10 and Bcl2 was significantly decreased. NAC can protect kidney tissue against DZN-induced toxicity by elevating antioxidants capacity, mitigating oxidative stress, inflammation and apoptosis.

Keywords

Acknowledgement

The authors of this manuscript wish to express their thanks and appreciation to Department of Nephrology and Immunology at Children's Hospital of Soochow University, and Department of Pediatrics at Affiliated Hospital of Yangzhou University, Yangzhou Jiangsu, China.

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