Preventive Effect ofThea sinensisMelanin against Acetaminophen-Induced Hepatic Injury in Mice

Abstract

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 Q9 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.

Characterization of melanin extracted from apricot (Armeniaca sibirica) and its effect on hydrazine-induced rat hepatic injury

“…Hydrazine challenge caused a significant increase in lipid peroxidation (measured as increases in MDA contents) in hepatic tissue of the rats, as previously observed 5,28,29 , to 1.27 ± 0.08 nmol/mg protein, indicating hydrazine intoxication (Fig. 9).…”

“…SOD plays a key role in elimination of reactive oxygen species (ROS) derived from the peroxidation of xenobiotics in hepatic tissues 26,29 . As shown in Fig.…”

“…Thus GSH deficiency in organisms can lead to tissue disorder and injury 29 . Significant reductions in GSH contents were detected in liver homogenates from hydrazine-treated rats (0.09 ± 0.04 g/mg protein versus 5.45 ± 0.74 g/mg protein in homogenates from controls).…”

“…CAT is a key component of the antioxidant defence system, inhibition of which results in enhanced sensitivity to free radicals and thus cellular damage 29 . As shown in Fig.…”

“…Partly because several kinds of free radicals are produced in the liver during their elimination, various deleterious agents can induce inflammation, fibrosis, necrosis, and eventually cirrhosis and functional deterioration of the organ 28 . Acute and chronic liver diseases are of global concerns, and medical treatments often involve difficult protocols and have limited efficiency 29 . Hence, there is considerable interest in complementary or alternative medicines for their treatment 26,30 , particularly drugs from natural products, which may have lower toxicity than synthetic drugs 5 .…”