Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway
Abstract Widespread application of carbendazim (CBZ) is a major environmental impact because of its residues that caused multi-organ dysfunction. Recently, Chitosan nanoparticles (CS-NPs) are extensively used as nanocarriers due to their non-toxic and biodegradable nature. Therefore, the current stu...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-06-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13960-1 |
| _version_ | 1811242256520183808 |
|---|---|
| author | Elshazly Mo Yasmin A. Ebedy Marwa A. Ibrahim Khaled Y. Farroh Eman I. Hassanen |
| author_facet | Elshazly Mo Yasmin A. Ebedy Marwa A. Ibrahim Khaled Y. Farroh Eman I. Hassanen |
| author_sort | Elshazly Mo |
| collection | DOAJ |
| description | Abstract Widespread application of carbendazim (CBZ) is a major environmental impact because of its residues that caused multi-organ dysfunction. Recently, Chitosan nanoparticles (CS-NPs) are extensively used as nanocarriers due to their non-toxic and biodegradable nature. Therefore, the current study aimed to investigate the possible mechanistic pathway of modified CS-NPs to reduce the hepatic and nephrotoxicity of CBZ in rats. CS-NPs were synthesized by the ionic gelation method by using ascorbic acid instead of acetic acid to increase its antioxidant efficiency. Twenty-adult male Wistar rats were grouped (n = 5) as follows: Group (1) negative control, group (2) received CS-NPs, group (3) received CBZ, and group (4) co-administered CS-NPs with CBZ. Rats received the aforementioned materials daily by oral gavage for 28 days and weighed weekly. The results revealed that CBZ receiving group showed severe histopathological alterations in the liver and kidney sections including cellular necrosis and interstitial inflammation confirmed by immunostaining and showed marked immunopositivity of iNOS and caspase-3 protein. There were marked elevations in the serum levels of ALT, AST, urea, and creatinine with a significant increase in MDA levels and decrease in TAC levels. Upregulation of the Keap1 gene and down-regulation of Nrf2 and HO-1 genes were also observed. Co-treatment of rats by CS-NPs with CBZ markedly improved all the above-mentioned toxicological parameters and return liver and kidney tissues to normal histological architecture. We concluded that CBZ caused hepatorenal toxicity via oxidative stress and the Nrf2/HO-1 pathway and CS-NPs could reduce CBZ toxicity via their antioxidant, anti-apoptotic, and anti-inflammatory effects. |
| first_indexed | 2024-04-12T13:49:03Z |
| format | Article |
| id | doaj.art-229a14965be141f7a6b41bf3ac1bbf25 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T13:49:03Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-229a14965be141f7a6b41bf3ac1bbf252022-12-22T03:30:35ZengNature PortfolioScientific Reports2045-23222022-06-0112111410.1038/s41598-022-13960-1Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathwayElshazly Mo0Yasmin A. Ebedy1Marwa A. Ibrahim2Khaled Y. Farroh3Eman I. Hassanen4Pathology Department, Faculty of Veterinary Medicine, Cairo UniversityPathology Department, Faculty of Veterinary Medicine, Cairo UniversityBiochemistry Department, Faculty of Veterinary Medicine, Cairo UniversityNanotechnology and Advanced Materials Central Lab, Agricultural Research CenterPathology Department, Faculty of Veterinary Medicine, Cairo UniversityAbstract Widespread application of carbendazim (CBZ) is a major environmental impact because of its residues that caused multi-organ dysfunction. Recently, Chitosan nanoparticles (CS-NPs) are extensively used as nanocarriers due to their non-toxic and biodegradable nature. Therefore, the current study aimed to investigate the possible mechanistic pathway of modified CS-NPs to reduce the hepatic and nephrotoxicity of CBZ in rats. CS-NPs were synthesized by the ionic gelation method by using ascorbic acid instead of acetic acid to increase its antioxidant efficiency. Twenty-adult male Wistar rats were grouped (n = 5) as follows: Group (1) negative control, group (2) received CS-NPs, group (3) received CBZ, and group (4) co-administered CS-NPs with CBZ. Rats received the aforementioned materials daily by oral gavage for 28 days and weighed weekly. The results revealed that CBZ receiving group showed severe histopathological alterations in the liver and kidney sections including cellular necrosis and interstitial inflammation confirmed by immunostaining and showed marked immunopositivity of iNOS and caspase-3 protein. There were marked elevations in the serum levels of ALT, AST, urea, and creatinine with a significant increase in MDA levels and decrease in TAC levels. Upregulation of the Keap1 gene and down-regulation of Nrf2 and HO-1 genes were also observed. Co-treatment of rats by CS-NPs with CBZ markedly improved all the above-mentioned toxicological parameters and return liver and kidney tissues to normal histological architecture. We concluded that CBZ caused hepatorenal toxicity via oxidative stress and the Nrf2/HO-1 pathway and CS-NPs could reduce CBZ toxicity via their antioxidant, anti-apoptotic, and anti-inflammatory effects.https://doi.org/10.1038/s41598-022-13960-1 |
| spellingShingle | Elshazly Mo Yasmin A. Ebedy Marwa A. Ibrahim Khaled Y. Farroh Eman I. Hassanen Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway Scientific Reports |
| title | Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway |
| title_full | Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway |
| title_fullStr | Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway |
| title_full_unstemmed | Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway |
| title_short | Newly synthesized chitosan-nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of Nrf2/HO1 signalling pathway |
| title_sort | newly synthesized chitosan nanoparticles attenuate carbendazim hepatorenal toxicity in rats via activation of nrf2 ho1 signalling pathway |
| url | https://doi.org/10.1038/s41598-022-13960-1 |
| work_keys_str_mv | AT elshazlymo newlysynthesizedchitosannanoparticlesattenuatecarbendazimhepatorenaltoxicityinratsviaactivationofnrf2ho1signallingpathway AT yasminaebedy newlysynthesizedchitosannanoparticlesattenuatecarbendazimhepatorenaltoxicityinratsviaactivationofnrf2ho1signallingpathway AT marwaaibrahim newlysynthesizedchitosannanoparticlesattenuatecarbendazimhepatorenaltoxicityinratsviaactivationofnrf2ho1signallingpathway AT khaledyfarroh newlysynthesizedchitosannanoparticlesattenuatecarbendazimhepatorenaltoxicityinratsviaactivationofnrf2ho1signallingpathway AT emanihassanen newlysynthesizedchitosannanoparticlesattenuatecarbendazimhepatorenaltoxicityinratsviaactivationofnrf2ho1signallingpathway |