[Protective effect of 2,4-dihydroxybenzophenone on cocaine-induced hepatotoxicity and neurotoxicity in mice].
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.


CONCLUSIONS
BP-1 has protective effect on acute hepatotoxicity and  neurotoxicity of mice induced by cocaine. Its mechanisms might be associated with its antioxidant activity.
Department of Toxicology, Peking University School of Public Health, Beijing, China.
Xue-yin
XY
Wu
Ru
R
Xue
Xin
X
Liu
Feng-lan
FL
Jia
Ming
M
Ruan
Bao-xu
BX
Zhang
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001577:Benzophenones / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003042:Cocaine / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*
D000975:Antioxidants; D001577:Benzophenones; D003042:Cocaine; C121479:2,4-dihydroxybenzophenone