Olayinka Ebenezer Tunde, Ore Ayokanmi, Ola Olaniyi Solomon, Adeyemo Oluwatobi Adewumi
Biochemistry Unit, Department of Chemical Sciences, Ajayi Crowther University, PMB 1066, Oyo, Oyo State 211213, Nigeria.
Med Sci (Basel). 2015 Sep 8;3(3):78-92. doi: 10.3390/medsci3030078.
Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180-200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated ( 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid.
环磷酰胺(CP)是一种用于化疗的双功能烷化剂,据报道可通过产生活性氧和氧化应激介导器官毒性。没食子酸(GA)是一种酚类物质,是一种具有经证实的自由基清除活性的天然抗氧化剂,可提供针对氧化损伤的保护作用。本研究旨在调查GA对CP诱导的大鼠毒性的改善作用。25只雄性Wistar大鼠(180 - 200克)被随机分为五个治疗组:(A)对照组,(B)CP组,2毫克/千克体重(b.w.),(C)GA预处理(20毫克/千克b.w.)7天,随后CP(2毫克/千克b.w.)7天,(D)GA(20毫克/千克b.w.)与CP(2毫克/千克b.w.)联合治疗7天,以及(E)GA(20毫克/千克b.w.)7天。CP诱导了明显的肾脏和肝脏损伤,因为与对照组相比,CP治疗组的血浆尿素、肌酐、胆红素水平以及AST、ALT、ALP和GGT活性显著升高(P < 0.05)。此外,与对照组相比,CP治疗组的肝脏GSH、维生素C水平以及SOD、过氧化氢酶和GST活性显著降低。这伴随着肝脏脂质过氧化的显著增加。GA预处理和联合治疗对肾脏和肝脏损伤标志物以及抗氧化指标和脂质过氧化的恢复清楚地表明,GA通过清除CP产生的活性氧发挥改善作用。这种保护作用可能归因于没食子酸的抗氧化特性。