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Preventive effect of Thea sinensis melanin against acetaminophen-induced hepatic injury in mice

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10.1021/jf049662o

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The preventive effect of Thea sinensis melanin (TSM) against overdoses of N-acetyl-p-aminophenol (NAPAP) was studied on ICR mice. Animals were given 400 mg/kg intraperitoneally (i.p.) of NAPAP, and TSM was injected i.p. in doses 10-40 mg/kg 2 h before intoxication. The protective effects were evidenced by a complete blockage of the NAPAP-induced elevation of plasma alanine aminotransferase (ALT) activity, decreased concentration of thiobarbituric acid reactive substances (TBARS) to the control level, and a partial prevention of reduced glutathione (GSH) depletion in the liver tissue. Preadministration of TSM also caused restoration of superoxide dismutase (SOD) activity and resumed content of coenzymes 09 and Q10. TSM by itself, however, did not affect the hepatic functional parameters, including serum ALT, TBARS, GSH, SOD, or coenzymes Q in the liver. Administration of TSM caused a dose-dependent inhibition of N-nitrosodimethylamine demethylase activity with ED50 of 15.8 mg/kg. Activities of ethoxyresorufin O-dealkylase and pentoxyresorufin O-alkylase isozymes were changed insignificantly. The immune suppressive effect of NAPAP on the in vivo antibody-forming cell responses was demonstrated using ICR-sensitized mice with sheep red blood cells. The joint effect of TSM and NAPAP indicated the capability of TSM to recover immunity of the animals to the level of intact mice. Results obtained demonstrate that TSM preadministration can prevent the multiple toxic effects of NAPAP.

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