Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats

Abstract

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 (p < 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.

Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide

“…Conversely, albumin was significantly decreased in CP-administered rats compared with control rats. Similar findings were reported by many authors, as cyclophosphamide was proved to cause significant increase of serum ALT, AST, and bilirubin (Olayinka, Ore, Ola, & Adeyemo, 2015;Li et al, 2015) and decreased albumin levels (Mahmoud & Al Dera, 2015).…”

“…Many investigations have reported that CP induces oxidative stress and reduces the antioxidant statues. Administration with CP was proven to cause a significant reduction of hepatic CAT, SOD, and GPx (Mahmoud, Hussein, & Ramadan, 2013;Mahmoud & Al Dera, 2015;Olayinka, Ore, Ola, & Adeyemo, 2015). Moreover, liver lipid peroxidation (LPO), estimated as MDA, showed a significant increase (P < 0.001) in CP-induced mice when compared to the control group (Li et al, 2015).…”

“…Therapeutic dose of CP causes hepatotoxicity, nephrotoxicity, cardiotoxicity, immunotoxicity, and mutagenicity (Chamorro-Cevallos et al, 2008;Viswanatha-Swamy et al, 2013;Amien, Fahmy, Abd-Elgleel, & Elaskalany, 2015;Li, Li, & Jia, 2015). Metabolism of CP leads to the formation of many cytotoxic metabolites that induce oxidative injury (Olayinka, Ore, Ola, & Adeyemo, 2015). The vital issue for both therapeutic and toxic effects of CP is the requirement of metabolic activation by hepatic microsomal cytochrome P450 mixed functional oxidase system (Cederbaum, 2015).…”

Ameliorative action of farnesol on cyclophosphamide induced toxicity in mice

“…The activities of the hepatic enzymes such as ALT and AST in the plasma are reliable indicators of hepatic injuries (32). Elevated plasma levels of these enzymes by CP resulted from cellular damages and loss of functional integrity of hepatocyte membrane leading to their leakage into the serum or plasma (9). AST is an enzyme abundant in the cytoplasm and mitochondria of hepatocytes and presents in heart, skeletal muscle, and brain.…”

“…The antineoplastic effects of CP are related to phosphoramide mustard, but acrolein is responsible for several toxic effects such as, induction of oxidative stress, cell death (apoptotic necrosis and oncotic necrosis) (4). Alleviation of toxic effects of CP in different organs has been investigated by using some antioxidant agents (5)(6)(7)(8)(9)(10)(11). Farnesol, a 15-carbon sesquiterpene ( Figure 1B), is produced in cells by dephosphorylation of farnesyl pyrophosphate (FPP), a metabolic precursor of squalene producing sterols and other isoprenoid compounds.…”