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Published on: February 18, 2016
[Protective effect of 2,4-dihydroxybenzophenone on cocaine-induced hepatotoxicity and neurotoxicity in mice]
1Department of Toxicology, Peking University School of Public Health, Beijing, China.
Objective:
To investigate the protective effect of 2,4-dihydroxybenzophenone(BP-1) on acute hepatotoxicity and neurotoxicity induced by cocaine in mice, and its possible mechanism.
Methods:
Male ICR mice were pretreated with BP-1(100,200,400 mg/kg, ig, 4 d), cocaine(75 mg/kg) was injected 30 minutes after BP-1 administration on day 4.Twenty-four hours after the injection of cocaine, the serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed by HITACHI-7170A automatic analyzer. The content of malondialdehyde (MDA) and the content of reduced glutathione (GSH) and oxidized glutathione (GSSG) were examined, and the ratio of GSH/GSSG was calculated, and histopathological analyses were also made. Male ICR mice were pretreated with BP-1(100,200,400 mg/kg, ig, 3 d), cocaine(20 mg/kg) was injected 30 minutes after BP-1 administration on day 3.The locomotor activity during 0-180 minutes of mice was recorded individually for each animal immediately after cocaine injection.
Results:
After the administration of cocaine, compared with corresponding solvent group, the activities of ALT [(1 571±1 161) IU/L vs. (30±16) IU/L, P<0.05], AST [(408±226) IU/L vs. (101±12) IU/L, P<0.05] and LDH [(3 963±1 431) IU/L vs. (1 935±287) IU/L, P<0.05] were significantly increased; the ratio of GSH/GSSG [(5.11±0.63) vs. (6.88±1.13),P<0.05] was decreased and the content of MDA [(1.97±1.36) μ mol/g vs. (0.07±0.06) μmol/g, P<0.01] was significantly increased. With the pretreatment of BP-1, compared with cocaine treatment group, the serum ALT [(112±96 )IU/L, (54±20) IU/L, (35±15) IU/L, P<0.05],AST [(130±33) IU/L,(107±5) IU/L, (99±9) IU/L, P<0.05] and LDH [(1 667±564) IU/L, (1 507±365) IU/L, (1 249±349) IU/L, P<0.01] were significantly decreased, the ratios of GSH/GSSG [(7.33±1.84), (9.28±0.67), (10.5±1.20), P<0.05] were increased and the contents of MDA [(1.82±1.19)μmol/g, (0.49±0.31)μmol/g, (0.35±0.30) μmol/g, P<0.05] were decreased. Significant amelioration in liver histopathology was also presented in the BP-1 treatment groups. The BP-1 pretreated mice showed significant reduction in activity counts evoked by cocaine (20 mg/kg), and shorten the time for activity counts to become normal.
Conclusion:
BP-1 has protective effect on acute hepatotoxicity and neurotoxicity of mice induced by cocaine. Its mechanisms might be associated with its antioxidant activity.
