الفهرس 
Liver in health and diseaseOnly 14 pages are availabe for public view
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Abstract
The present study was conducted to evaluate the effect of thymoquinone, a natural main constituent of the volatile oil of Nigella sativa seeds, in modulation of the disturbed hepatic function induced by D-galactosamine. The hepatic functional and histopathological changes were examined and compared with silymarin, a standard hepatoprotective drug.
This study was performed on 44 female Wistar rats, divided into four groups.
Group I: Normal control group (n=11)
Rats received olive oil by gavage in a dose of 2 ml/kg b.w., for 10 days. On the tenth day, 2 hours after olive oil administration, rats received single, i.p., injection of normal saline in a dose of 1.5 ml/kg b.w., then they were sacrificed 22 hours later.
Group II: D-galactosamine control group (n=11)
Rats received olive oil by gavage in a dose of 2 ml/kg b.w, for 10 days. On the tenth day, 2 hours after olive oil administration, rats received single, i.p., injection of D-galactosamine in a dose of 400 mg, dissolved in 1.5 ml normal saline, per kg b.w., then they were sacrificed 22 hours later..
Group III: Thymoquinone-D-galactosamine- treated group (n=11)
Rats received thymoquinone, in a dose of 20 mg dissolved in 2 ml olive oil, per kg b.w., by gavage for 10 days. On the tenth day, 2 hours after thymoquinone administration, rats received single, i.p., injection of D-galactosamine in a dose of 400 mg dissolved in 1.5 normal saline, per kg b.w., then they were sacrificed 22 hours later.
Group IV: Silymarin-D-galactosamine-treated group (n=11)
Rats received silymarin in a dose of 25 mg dissolved in 2 ml olive oil, per kg b.w., by gavage for 10 days. On the tenth day, 2 hours after silymarin administration, rats received single, i.p., injection of D-galactosamine in a dose of 400 mg dissolved in 1.5 ml normal saline, per kg b.w., then they were sacrificed 22 hours later.
Rats of the four groups were subjected to measurement of plasma levels of total proteins, albumin, alanine transferase (ALT), aspartate transferase (AST), and lactate dehydrogenase (LDH), as well as blood levels of reduced glutathione (GSH) and hepatic levels of GSH and malondialdehyde (MDA). Also, livers were subjected to histological study.
D-galactosamine rats demonstrated decreased plasma total proteins and albumin, elevated plasma levels of liver enzymes; ALT, AST and LDH, and as well decreased hepatic GSH content and increased hepatic MDA levels compared to normal control rats. In addition, histological examination revealed loss of the normal hepatic architecture, with vacuolar degeneration, necrosis of hepatocytes, and inflammatory cell infiltration.
Upon pretreatment with thymoquinone, a marked reduction was observed in the elevated plasma levels of ALT, AST, and LDH and in the elevated hepatic MDA levels induced by D-galactosamine; the reduction was comparable to that produced by silymarin. On the other hand, plasma total proteins and albumin, and hepatic GSH content showed slight insignificant rise with thymoquinone treatment, in contrast to a significant rise in these parameters with silymarin treatment, reaching to the normal control values. Meanwhile, focal and bridging necrosis, eosinophility of hepatocytes, and inflammatory cell infiltration induced by D-galactosamine were reduced by pretreatment with thymoquinone, however, more reduction was observed with silymarin, yet it was nonsignificantly different compared to thymoquinone.
In conclusion, pretreatment with thymoquinone in a dose 20mg/kg, b.w., for 10 days, protected the liver enzyme leakage and prevented lipid peroxidation induced by D-galactosamine injection to the same extent as silymarin. These findings indicate the membrane stabilizing effect of thymoquinone that might be ascribed to its ability to scavenge the free radicals derived from D-galactosamine and therefore protect the liver from oxidative damage.
However, the magnitude of protection offered by thymoquinone was less than that of silymarin, evident by the significant increase in plasma albumin level and hepatic GSH content with silymarin compared to thymoquinone.
Thus, further studies with higher doses of thymoquinone and for longer duration are necessary to determine the effective dose and to assess its value as a promising prophylactic agent against hepatic dysfunction.