The hepatoprotective and antioxidative effect of saffron stigma alcoholic extract against vincristine sulfate induced toxicity in rats

Abstract

Vincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.

Keywords: hepatotoxicity; liver enzymes; oxidative stress; saffron; vincristine.

Figure 1

A: Comparison of AST activity between all groups (mean and SEM). There is a significant difference in mean AST activity between all groups (p<0.001). Saffron treatment decreased the vincristine-induced AST activity especially at higher concentration. V: vincristine; S: saffron. B: Comparison of the ALT activity between all groups (mean and SEM). There is a significant difference in mean of ALT activity between all groups (p<0.001). Saffron treatment decreased the vincristine-induced ALT activity. V: vincristine; S: saffron. C: Comparison of ALP activity between all groups (mean and SEM). There is a significant difference in mean ALP activity between all groups (p<0.001). Saffron treatment decreased the vincristine-induced ALP activity especially at higher concentrations. V: vincristine; S: saffron. D: Comparison of the bilirubin levels between all groups (mean and SEM). There is a significant difference in mean bilirubin concentration between all groups (p<0.001). Saffron treatment decreased the vincristine-induced bilirubin concentration. V: vincristine; S: saffron. E: Comparison of TAC mean levels between all groups (mean and SEM). There is a significant difference in mean TAC concentration between all groups (p<0.001). Saffron treatment increased the TAC values in VCR treated rats. V: vincristine; S: saffron; TAC: total antioxidant capacity. F: Comparison of MDA mean levels between all groups (mean and SEM). There is a significant difference in mean MDA concentration between all groups (p<0.001). Saffron treatment reduced the MDA values in VCR treated rats. V: vincristine; S: saffron; MDA: malondialdehyde.