Phenolic Acids (Gallic and Tannic Acids) Modulate Antioxidant Status and Cisplatin Induced Nephrotoxicity in Rats

Abstract

Cisplatin (cis-diamminedichloroplatinum (II) or CDDP), used in the treatment of many solid-tissue cancers, has its chief side-effect in nephrotoxicity. Hence, this study sought to investigate and compare the protective effect of gallic acid (GA) and tannic acid (TA) against cisplatin induced nephrotoxicity in rats. The rats were given a prophylactic treatment of GA and TA orally at a dose of 20 and 40 mg/kg body weight for 7 consecutive days before the administration of a single intraperitoneal (i.p.) injection of cisplatin (CP) at 7.5 mg/kg bwt. The protective effects of both GA and TA on CP induced nephrotoxicity were investigated by assaying renal function, oxidative stress biomarkers, and histopathological examination of kidney architecture. A single dose of cisplatin (7.5 mg/kg bwt) injected i.p. caused a significant increase in some biomarkers of renal function (creatinine, uric acid, and urea levels), with a marked elevation in malondialdehyde (MDA) content accompanied by a significant (P < 0.05) decrease in reduced glutathione (GSH) content (103.27%) of kidney tissue as compared to control group. Furthermore, a significant (P < 0.05) reduction in kidney antioxidant enzymes (SOD, catalase, GPx, and GST) activity was observed. However, pretreatment with oral administration of tannic acid and gallic acid at a dose of 20 and 40 mg/kg body weight, respectively, for 7 days prior to cisplatin administration reduced histological renal damage and suppressed the generation of ROS, lipid peroxidation, and oxidative stress in kidney tissues. These results indicate that both gallic and tannic acids could serve as a preventive strategy against cisplatin induced nephrotoxicity.

Figure 1

Effect of gallic and tannic acids on kidney and plasma MDA contents in normal and cisplatin induced nephrotoxic rats. 1: Normal control; 2: Induced control, 3: 20 mg gallic acid + cisplatin, 4: 40 mg gallic acid + cisplatin, 5: 40 mg gallic acid only, 6: 20 mg tannic acid + cisplatin, 7: 40 mg tannic acid + cisplatin, and 8: 40 mg tannic acid only. ^{∗, #} Significantly different (P < 0.05) from the normal control; ^&,∧Significantly (P < 0.05) different from the induced control.

Figure 2

Effect of gallic and tannic acids on arginase activity in the kidney of normal and cisplatin induced nephrotoxic rats. 1: Normal control; 2: Induced control, 3: 20 mg gallic acid + cisplatin, 4: 40 mg gallic acid + cisplatin, 5: 40 mg gallic acid only, 6: 20 mg tannic acid + cisplatin, 7: 40 mg tannic acid + cisplatin, and 8: 40 mg tannic acid only. ^* Significantly (P < 0.05) different from the normal control; ^#Significantly (P < 0.05) different from the induced control.

Figure 3

Histopathological views (×400) of the kidney showing severe and generalized tubular epithelial cell necrosis associated with diffuse tubular lumina in rat administered a single i.p dose of cisplatin (7.5 mg/kg bwt) (b), while no damage is noticed in normal control rats (a).

Figure 4

Histopathological views (×400) of the kidney showing a marked improvement on kidney damage in rats pretreated with gallic and tannic acids. ((a) and (b)) gallic acid (20 and 40 mg/kg bwt) + cisplatin and ((c) and (d)) tannic acid (20 and 40 mg/kg bwt) + cisplatin.

Figure 5

Histopathological views (×400) of the kidney showing no damage in rats pretreated with gallic acid (40 mg/kg bwt) (a) and tannic acid (40 mg/kg bwt) (b) only without cisplatin.