Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney

Abstract

Cyclophosphamide (CP) is an antineoplastic drug that induces kidney damage via producing oxidative stress. Carvacrol (CAR) has antioxidative effect and we postulated that it can be protective against CP-induced nephrotoxicity. Six groups (n = 7) of rats (control, 100 mg/kg CP, CP+5 mg/kg CAR, CP+10 mg/kg CAR, 5 mg/kg CAR, and 10 mg/kg CAR) were injected intraperitoneally. Serum malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), creatinine (CRE), total antioxidant capacity (TAC), and total oxidant state (TOS) were measured, and oxidative stress indexes (OSI) were calculated. Kidneys were also analyzed histologically. In CP-alone group MDA, CRE, TOS, and OSI levels increased whereas GSH, SOD, CAT, and TAC levels decreased compared with control group. In CP plus CAR groups, MDA, TOS, and OSI levels decreased whereas GSH, SOD, CAT, and TAC levels increased compared with CP-alone group. However, CRE levels were similar in CP-alone and CP+5 CAR group whereas decreased in CP+10 CAR group. CP+10 CAR group was significantly different in all parameters (except TAC) from CP+5 CAR group. Kidney microscopy was showed lower tissue damage in CP plus CAR groups. In conclusion, 10 mg/kg CAR is more effective than 5 mg/kg CAR in prevention of CP-induced oxidative damage on kidney.

Contribution of garlic for improving the cytoprotective effect of mesna against cyclophosphamide toxicity in rats

“…injection of CYP. Inconsistent with our findings, Gunes et al [30] recorded that rats treated with 100 mg/kg CYP induced significant increase in serum MDA with reduction in TAC. Moreover, previous investigations recorded the tissue oxidative damages of CYP as demonstrated by increase of MDA and reduction of antioxidants [28,[31][32][33][34][35].…”

“…The mechanism by which CYP induces tissue damages could be attributed it to its cytotoxic metabolites; phosphoramide mustard and acrolein. Phosphoramide mustard exerts antineoplastic effect while acrolein, is a highly reactive metabolite that causes oxidative stress implicated in the urotoxic, hepatotoxic, nephrotoxic, cardiotoxic and immunotoxic effects of CYP [28,[30][31][32]34,38]. Also, CYP cytotoxicity may be due to the production of TNF-α, a pleiotropic cytokine inducing cell death via necrosis and apoptosis pathway [39].…”

Candesartan in a rat model of testicular toxicity: New insight on its protective mechanism

“…20 OSI (Arbitrary Unit; AU) = TOS (μmol H 2 O 2 equivalent/mg protein)/TAS (mmol Trolox equivalent/mg protein) × 100. 21…”

Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato–Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice

“…CP is a prodrug that is metabolized within hepatocytes to generate two reactive metabolites, phosphoramide mustard and acrolein [7]. Phosphoramide mustard possesses antineoplastic activity, while acrolein is reported to be responsible for the CP-induced cytotoxic effects [8,9]. Acrolein initiates oxidative stress via the production of reactive oxygen species (ROS) causing the depletion of cellular defense mechanisms, induction of lipid peroxidation [10], nucleic acid damage and mutation [11].…”