Carvacrol attenuates acute kidney injury induced by cisplatin through suppression of ERK and PI3K/Akt activation.
We investigated the mechanisms of renoprotective effects of carvacrol, a monoterpenoid compound, against cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 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, renal oxidative stress was evidenced by increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), 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 kidneys, suggesting inflammatory response. CP intoxication induced apoptosis and inhibition of the cell cycle in 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 and PI3K/Akt pathways.
Department of Chemistry and Biochemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Iva
I
Potočnjak
Department of Chemistry and Biochemistry, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. Electronic address: robert.domitrovic@uniri.hr.
Robert
R
Domitrović
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D000081007:Cymenes; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D002945:Cisplatin; D000081007:Cymenes; D048049:Extracellular Signal-Regulated MAP Kinases; D039821:Monoterpenes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C073316:carvacrol
Apoptosis; Carvacrol; Cisplatin nephrotoxicity; ERK; Inflammation; PI3K/Akt