Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats
Irinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. <i>N</i>-acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress a...
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2219 |
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| author | Sevgi Gençosman Deniz Ceylanlı Ahmet Özer Şehirli Kerem Teralı Furkan Bölükbaşı Şule Çetinel Serkan Sayıner |
| author_facet | Sevgi Gençosman Deniz Ceylanlı Ahmet Özer Şehirli Kerem Teralı Furkan Bölükbaşı Şule Çetinel Serkan Sayıner |
| author_sort | Sevgi Gençosman |
| collection | DOAJ |
| description | Irinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. <i>N</i>-acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress and inflammation. This study aimed at investigating whether NAC provides protection against hepatorenal and gastrointestinal tissue damage induced by CPT-11. Thirty-two Wistar albino rats were divided into four groups as control, NAC, CPT-11, and CPT-11+NAC. Following the experimental period, blood, and tissue samples (liver, kidney, stomach, and small intestine) were collected, and biochemical indicators, together with pro-inflammatory cytokines (TNF-α and IL-1β), matrix metalloproteinases (MMPs), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels were evaluated. Both the biochemical indicators and the pro-inflammatory cytokines, MMP, and MDA levels increased in animals treated with CPT-11, while SOD and GPx activities decreased. Histopathological evaluation revealed structural damage in all examined tissues. With NAC administration, significant improvements were observed, both biochemically and histologically. In conclusion, the results of the present study suggest that NAC treatment together with CPT-11 may have a beneficial effect on reducing CPT-11 toxicity in rats, by modulating inflammation and the oxidant–antioxidant balance. These results strongly promote further investigative studies. |
| first_indexed | 2024-03-09T18:31:26Z |
| format | Article |
| id | doaj.art-9a09f97c0c354455b151da39b62276b6 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T18:31:26Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-9a09f97c0c354455b151da39b62276b62023-11-24T07:31:42ZengMDPI AGAntioxidants2076-39212022-11-011111221910.3390/antiox11112219Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in RatsSevgi Gençosman0Deniz Ceylanlı1Ahmet Özer Şehirli2Kerem Teralı3Furkan Bölükbaşı4Şule Çetinel5Serkan Sayıner6Department of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, TurkeyDepartment of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, TurkeyDepartment of Pharmacology, Faculty of Dentistry, Near East University, 99138 Nicosia, North Cyprus, TurkeyDepartment of Medical Biochemistry, Faculty of Medicine, Cyprus International University, 99258 Nicosia, North Cyprus, TurkeyDepartment of Histology and Embryology, School of Medicine, Marmara University, 34722 İstanbul, TurkeyDepartment of Histology and Embryology, School of Medicine, Marmara University, 34722 İstanbul, TurkeyDepartment of Biochemistry, Faculty of Veterinary Medicine, Near East University, 99138 Nicosia, North Cyprus, TurkeyIrinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. <i>N</i>-acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress and inflammation. This study aimed at investigating whether NAC provides protection against hepatorenal and gastrointestinal tissue damage induced by CPT-11. Thirty-two Wistar albino rats were divided into four groups as control, NAC, CPT-11, and CPT-11+NAC. Following the experimental period, blood, and tissue samples (liver, kidney, stomach, and small intestine) were collected, and biochemical indicators, together with pro-inflammatory cytokines (TNF-α and IL-1β), matrix metalloproteinases (MMPs), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels were evaluated. Both the biochemical indicators and the pro-inflammatory cytokines, MMP, and MDA levels increased in animals treated with CPT-11, while SOD and GPx activities decreased. Histopathological evaluation revealed structural damage in all examined tissues. With NAC administration, significant improvements were observed, both biochemically and histologically. In conclusion, the results of the present study suggest that NAC treatment together with CPT-11 may have a beneficial effect on reducing CPT-11 toxicity in rats, by modulating inflammation and the oxidant–antioxidant balance. These results strongly promote further investigative studies.https://www.mdpi.com/2076-3921/11/11/2219cancer chemotherapyirinotecan<i>N</i>-acetylcysteinematrix metalloproteinaseproinflammatory cytokinesmalondialdehyde |
| spellingShingle | Sevgi Gençosman Deniz Ceylanlı Ahmet Özer Şehirli Kerem Teralı Furkan Bölükbaşı Şule Çetinel Serkan Sayıner Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats Antioxidants cancer chemotherapy irinotecan <i>N</i>-acetylcysteine matrix metalloproteinase proinflammatory cytokines malondialdehyde |
| title | Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats |
| title_full | Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats |
| title_fullStr | Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats |
| title_full_unstemmed | Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats |
| title_short | Investigation of the Possible Protective Effect of <i>N</i>-Acetylcysteine (NAC) against Irinotecan (CPT-11)-Induced Toxicity in Rats |
| title_sort | investigation of the possible protective effect of i n i acetylcysteine nac against irinotecan cpt 11 induced toxicity in rats |
| topic | cancer chemotherapy irinotecan <i>N</i>-acetylcysteine matrix metalloproteinase proinflammatory cytokines malondialdehyde |
| url | https://www.mdpi.com/2076-3921/11/11/2219 |
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