Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Sep 8;3(3):78-92.
doi: 10.3390/medsci3030078.

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

Ebenezer Tunde Olayinka  1 , Ayokanmi Ore  2 , Olaniyi Solomon Ola  3 , Oluwatobi Adewumi Adeyemo  4
Affiliations

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

Ebenezer Tunde Olayinka et al. Med Sci (Basel). .

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.

Keywords: cyclophosphamide; gallic acid; hepatic dysfunction; oxidative injury.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of cyclophosphamide (a), and gallic acid (b).
Figure 2
Figure 2
Protective effects of gallic acid on cyclophosphamide induced changes in the activity of hepatic glutathione-S-transferase (GST) in rats. CP = cyclophosphamide (2 mg/kg body weight); GA = gallic acid (20 mg/kg body weight); Data are expressed as mean ±SD for five rats in each group; * Significantly different from the control (p < 0.05); a Significantly different from cyclophosphamide group.
Figure 3
Figure 3
Protective effects of gallic acid on cyclophosphamide induced changes in the levels of hepatic ascorbic acid in rats. CP = cyclophosphamide (2 mg/kg body weight); GA = gallic acid (20 mg/kg body weight); Data are expressed as mean ±SD for five rats in each group; * Significantly different from the control (p < 0.05); a Significantly different from cyclophosphamide group.
Figure 4
Figure 4
Protective effects of gallic acid on cyclophosphamide induced changes in the levels of hepatic reduced glutathione (GSH) concentration in rats. CP = cyclophosphamide (2 mg/kg body weight); GA = gallic acid (20 mg/kg body weight); Data are expressed as mean ±SD for five rats in each group; * Significantly different from the control (p < 0.05); a Significantly different from cyclophosphamide group.
Figure 5
Figure 5
Protective effects of gallic acid on cyclophosphamide induced changes in the levels of hepatic Lipid peroxidation in rats. CP = cyclophosphamide (2 mg/kg body weight); GA = gallic acid (20 mg/kg body weight); Data are expressed as mean ±SD for five rats in each group; * Significantly different from the control (p < 0.05); a Significantly different from cyclophosphamide group.
See this image and copyright information in PMC

References

    1. Takimoto C.H., Calvo E. Principles of oncologic pharmacotherapy. In: Pazdur R., Coia L.R., Hoskins W.J., Wagman L.D., editors. Cancer Management: A Multidisciplinary Approach. 9th ed. PRR Inc.; Seattle, WA, USA: 2005. pp. 23–42.
    1. Clern M., Bickers D.R. Dermatological pharmacology. In: Goodman G.A., Rall T.W., Nies A.S., Taylor P., editors. The Pharmacological Basis of Therapeutics. Pergamon Press; New York, NY, USA: 1991. pp. 1572–1591.
    1. Paul C., Bruce A.C. Antineoplastic agents. In: Goodman G.A., Rall T.W., Nies A.S., Taylor P., editors. The Pharmacological Basis of Therapeutics. Pergamon Press; New York, NY, USA: 1991. pp. 1209–1263.
    1. Kirkland R.T., Bongiovanni A.M., Cornfield D., McCormic J.B., Parks J.S., Tenore A. Gonadotropin responses to leutinizing releasing factor in boys treated with cyclophosphamide for nephrotic syndrome. J. Pediatr. 1976;89:941–944. doi: 10.1016/S0022-3476(76)80600-2. - DOI - PubMed
    1. Etteldorf J.N., West C.D., Pitcock J.A., Williams D.L. Gonadal function, testicular histology, and meiosis following cyclophosphamide therapy in patients with nephrotic syndrome. J. Pediatr. 1976;88:206–212. doi: 10.1016/S0022-3476(76)80983-3. - DOI - PubMed

LinkOut - more resources