Journals / Turkish Journal of Medical Sciences / 2019 / Cilt: 49 - Sayı: 6

The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model

Pages
1789–1799
Publication Date
2022-11-06
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion:It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Background/Aim:Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers.
📊
Key Findings & Data:Of those, the most clinically significant and common effect is nephrotoxicity.
💡
Conclusion & Impact:Conclusion:It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Background/Aim:Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental groups were treated intraperitoneally (i.p.) with a single dose of cisplatin (10 mg/kg body weight) and i.p. with NAC (250 mg/kg body weight) for three consecutive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples, myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB), high mobility group box-1 (HMGB-1), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well. Results: It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but did increase TOS levels and decrease TAS levels in tissue samples. Interestingly, NAC elevated MPO and HMGB-1 levels significantly. Nevertheless, NAC ameliorated histological and functional changes in kidney tissues. Conclusion:It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.

🔖

Cite This Article

YAZICI, C., KÖSE, K., DAĞLI, F., YAY, A., YÜCEL, B., GÜNTÜRK, İ. (2022). The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model. Turkish Journal of Medical Sciences, Cilt: 49 - Sayı: 6, 1789–1799. https://ajindex.com/articles/609973

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (15)

  1. Perše M, Večerić-Haler Ž. Cisplatin-induced rodent model of kidney injury: characteristics and challenges. BioMed Research International 2018; 2018: 1462802
  2. Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nature Reviews Drug Discovery 2005; 4: 307-320
  3. Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. American Journal of the Medical Sciences 2007; 334: 115-124
  4. Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 2011; 3: 1351-1371
  5. Sánchez-González PD, López-Hernández FJ, López-Novoa JM, Morales AI. An integrative view of the pathophysiological events leading to cisplatin nephrotoxicity. Critical Reviews in Toxicology 2011; 41: 803-821
  6. Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Veterinary and Comparative Oncology 2008; 6: 1-18
  7. Uozumi J, Ueda T, Yasumasu T, Koikawa Y, Naito S et al. Platinum accumulation in the kidney and changes in creatinine clearance following chemotherapy with cisplatin in humans. Urologia Internationalis 1993; 51: 57-61
  8. Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochimica et Biophysica Acta - General Subjects 2013; 1830: 4117-4129
  9. Atkuri KR, Mantovani JJ, Herzenberg LA, Herzenberg LA. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology 2007; 7: 355- 359
  10. Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences 2003; 60: 6-20
  11. Muldoon LL, Wu YJ, Pagel MA, Neuwelt EA. N-Acetylcysteine chemoprotection without decreased cisplatin antitumor efficacy in pediatric tumor models. Journal of Neuro-Oncology 2015; 121: 433-440
  12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 1951; 193: 265-275
  13. Abdelrahman AM, Al Salam S, Al Mahruqi AS, Al Husseni IS, Mansour MA et al. N-Acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity. Journal of Applied Toxicology 2010; 30: 15-21
  14. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel) 2010; 2: 2490-2518
  15. Hayati F, Hossainzadeh M, Shayanpour S, Abedi-Gheshlaghi Z, Beladi Mousavi SS. Prevention of cisplatin nephrotoxic