engleski

Carvacrol attenuates acute kidney injury induced by cisplatin through suppression of MAPK and PI3K/Akt pathways

Mechanisms of renoprotective effects of carvacrol against cisplatin (CP)-induced kidney injury were investigated. Male BALB/cN mice were orally gavaged with 5, 10 and 20 mg carvacrol/kg body weight for two days, 48 h after CP (13mg/kg) intraperitoneal injection. Four days after CP administration, the increase in serum creatinine and blood urea nitrogen levels coincided with histopathological findings of kidney injury. Renal oxidative stress was evidenced by increased expression of cytochrome P450 E1 (CYP2E1) and heme oxygenase- 1 (HO-1). CP treatment increased the expression of phosphorylated nuclear factor-kappaB (NF-κB) p65 and tumor necrosis factor-alpha (TNF-α) in the kidneys, suggesting inflammatory response. CP intoxication induced apoptosis and inhibition of the cell cycle in the kidneys by increasing the expression of p53, p21, Bax, and caspase-3 and suppressing Bcl-2 and cyclin D1 expression. The increase in proliferating cell nuclear antigen (PCNA) suggested enhancement of DNA repair process. CP administration also resulted in activation of extracellular signal- regulated kinases 1 and 2 (ERK1/2), Akt and signal transducer and activator of transcription (STAT) 3. All these changes were dose- dependently restored by carvacrol. In vitro, carvacrol at concentration of 550 μM showed a significant cytotoxicity against HeLa cells, which occured through ERK1/2 inhibition. Interestingly, carvacrol seems to protect HeLa cells treated by CP. The results of the current study suggest that carvacrol attenuated CP- induced acute renal injury by suppressing oxidative stress, apoptosis and inflammation through the mechanisms which involve modulation of PI3K/Akt and ERK/STAT3 pathways. However, some concerns arose concerning its cytoprotection against CP-treated tumor cells in vitro.

cisplatin ; carvacrol ; MAPK ; kidney ; HeLa cells

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