Expression of ER stress markers (GRP78 and PERK) in experimental nephrotoxicity induced by cisplatin and gentamicin: Roles of inflammatory response and oxidative stress
Yükleniyor...
Dosyalar
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated
protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin
(CIS)–induced and gentamicin (GEN)–induced nephrotoxicity.
The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for
7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last
injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.
CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS),
while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural
findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor
necrosis factor-α (TNF-α) and interleukin 1β (IL-1β)) and ER stress markers (GRP78 and PERK) was significantly increased
in the kidney tissue of rats treated with CIS and GEN for 7 days.
These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of
oxidative stress, inflammation, and ER stress–related markers. As a result, the recommended course of action is to utilize
CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs instead
Açıklama
This work was supported by Kahramanmaras Sutcu Imam University Department of Scientific Research Projects (grant number: 2017/4-40 M).
Anahtar Kelimeler
Nephrotoxicity, Cisplatin, Gentamicin, ER Stress, GRP78/BIP, PERK
Kaynak
Naunyn-Schmiedeberg's Archives of Pharmacology
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
396
Sayı
4
Künye
Metin, T. O., Bayrak, G., Yaman, S., Doganer, A., Yoldas, A., Eser, N., ... & Sahin, M. (2023). Expression of ER stress markers (GRP78 and PERK) in experimental nephrotoxicity induced by cisplatin and gentamicin: Roles of inflammatory response and oxidative stress. Naunyn-Schmiedeberg's Archives of Pharmacology, 396(4), 789-801. https://doi.org/10.1007/s00210-022-02358-5
