The effects of apelin-13 against cisplatin-induced nephrotoxicity in rats.


TOPÇU A., SARAL S., MERCANTEPE T., AKYILDIZ K., TÜMKAYA L., YILMAZ A.

Drug and chemical toxicology, pp.1-11, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume:
  • Publication Date: 2021
  • Doi Number: 10.1080/01480545.2021.2011309
  • Journal Name: Drug and chemical toxicology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1-11
  • Keywords: Apelin-13, cisplatin, inflammation, nephrotoxicity, oxidative stress, rats, OXIDATIVE STRESS, INFLAMMATION, PRETREATMENT, INHIBITION, MECHANISMS, APOPTOSIS, AUTOPHAGY, PROTECTS, PATHWAY, IMPACT
  • Recep Tayyip Erdoğan University Affiliated: Yes

Abstract

Acute kidney injury (AKI) is observed in nearly 60% of patients undergoing cisplatin (CP) therapy. The aim of this study was to reveal the potential effects of apelin-13 (AP-13) in the prevention of CP-induced renal toxicity, together with its antioxidant and anti-inflammatory effect mechanisms. Four experimental groups were established. Group 1, the control group, received 0.9% saline solution alone intraperitoneally (IP). Group 2, the CP group, received CP IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 3, the CP + Apelin-13 (AP-13) group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free saline before injection every day for four weeks and administered IP. CP was administered IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 4, the AP-13 group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free 0.9% saline before injection every day for four weeks and administered IP. Thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin-1 beta, cleaved caspase-3, 8-hydroxy 2-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-kappa beta/p65) levels were then measured. Increased oxidative stress, inflammation, and apoptosis as a result of CP application activated the cascade. However, AP-13 administration reduced the oxidative stress increased by CIS with the determined antioxidant effect and reduced the damage by increasing total -SH levels. 8-OHdG and NF-kappa beta/p65, which were up-regulated by triggering oxidative stress and inflammation, were down-regulated through the antioxidant and anti-inflammatory effects of AP-13.