Lercanidipine alleviates doxorubicin-induced lung injury by regulating PERK/CHOP and Bax/Bcl 2/Cyt c pathways

TEPEBAŞI M. Y., Selli J., Gül S., Hüseynov İ., Milletsever A., Selçuk E.

Histochemistry and Cell Biology, vol.160, no.4, pp.361-368, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 160 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.1007/s00418-023-02231-3
  • Journal Name: Histochemistry and Cell Biology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, CINAHL, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.361-368
  • Keywords: Apoptosis, Doxorubicin, Lercanidipine, Lung toxicity, Oxidative stress
  • Süleyman Demirel University Affiliated: Yes


Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model.