engleski

Carvacrol attenuates kidney apoptosis induced by cisplatin through suppression of the ERK MAPK and PI3K/Akt pathways

Carvacrol has been shown to possess numerous health beneficial effects. In this study we investigated the mechanisms of renoprotective effects of carvacrol against cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally gavaged with 1, 3, and 10 mg carvacrol/kg body weight for two days, 48 h after intraperitoneal injection of CP (13 mg/kg). Four days after CP administration, the increase in serum creatinine and blood urea nitrogen (BUN) 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 (p-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 and Bax and suppressing Bcl-2 and cyclin D1 expression. Concomitant increase in p21 and proliferating cell nuclear antigen (PCNA) expression suggested enhanced DNA repair process. CP administration also resulted in activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) with concomitant induction of phosphorylated Akt and suppression of phosphatase and tensin homolog (PTEN) expression. All these changes were dose-dependently restored by carvacrol. The results of the current study suggest that carvacrol could attenuate CP-induced acute renal injury by suppressing oxidative stress, apoptosis and inflammation through modulation of the ERK MAPK and PI3K/Akt pathways.

carvacrol ; cisplatin nephrotoxicity ; apoptosis ; inflammation ; MAPK ; PI3K/Akt

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