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. 2016 Aug 26;6(1):6092.
doi: 10.4081/xeno.2016.6092. eCollection 2016 Jun 10.

Ameliorative Effect of Gallic Acid on Methotrexate-Induced Hepatotoxicity and Nephrotoxicity in Rat

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

Ameliorative Effect of Gallic Acid on Methotrexate-Induced Hepatotoxicity and Nephrotoxicity in Rat

Ebenezer Tunde Olayinka et al. J Xenobiot. .

Abstract

We investigated the protective effect of gallic acid (GA) against methotrexate (MTX)-induced hepatotoxicity and nephrotoxicity. Male Wistar rats were randomized into five groups (n = 6/group): I, control; II, MTX-treated for seven days; III, pre-treated with GA for seven days, followed by MTX for seven days; IV, co-treated with MTX and GA for seven days and V, GA for seven days. MTX caused a significant increase (P<0.05) in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (Bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase) when compared with control. Furthermore, MTX caused a significant decrease in the activities of hepatic enzymic antioxidants (superoxide dismutase, catalase, glutathione S-transferase) and nonenzymic antioxidants (Vitamin C and glutathione), followed by a significant increase in hepatic malondialdehyde content. However, pre-treatment and co-treatment with gallic acid ameliorated the MTX-induced biochemical changes observed. Taken together, GA protected against MTX-induced hepatotoxicity and nephrotoxicity in rats, by reducing the impact of oxidative damage to tissues.

Keywords: Methotrexate; gallic acid; hepatotoxicity; nephrotoxicity; rat.

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Figures

Figure 1.
Figure 1.
Chemical structure of methotrexate (A) and gallic acid (B).
Figure 2.
Figure 2.
Ameliorative effect of gallic acid pre-treatment and co-treatment on methotrexate-induced reduction in hepatic glutathione S-transferase (GST) activity in rats. Data are expressed as mean ± S.D for six rats in each group. *Significantly different from the control (P<0.05); asignificantly different from the methotrexate group (P<0.05).
Figure 3.
Figure 3.
Ameliorative effect of gallic acid pre-treatment and co-treatment on methotrexate-induced reduction in hepatic vitamin C level in rats. Data are expressed as mean ± S.D for six rats in each group. *Significantly different from the control (P<0.05); asignificantly different from the methotrexate group (P<0.05).
Figure 4.
Figure 4.
Ameliorative effect of gallic acid pre-treatment and co-treatment on methotrexate-induced reduction in hepatic glutathione (GSH) level in rats. Data are expressed as mean ± S.D for six rats in each group. *Significantly different from the control (P<0.05); asignificantly different from the methotrexate group (P<0.05).
Figure 5.
Figure 5.
Ameliorative effect of gallic acid pre-treatment and co-treatment on methotrexate-induced increase in hepatic level of lipid peroxidation (MDA) in rats. Data are expressed as mean ± S.D for six rats in each group. *Significantly different from the control (P<0.05); asignificantly different from the methotrexate group (P<0.05).
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