Effects of volatile oil constituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: evidence for antioxidant effects of thymoquinone.
Effects of the volatile oil constituents of Nigella sativa, namely, thymoquinone (TQ), p-cymene and alpha-pinene, on carbon tetrachloride (CCl4-indued acute liver injury were investigated in mice. A single dose of CCl4 (15 microl/Kg i.p.) induced hepatotoxicity 24 h after administration manifested biochemically as significant elevation of the enzymes activities of serum alanine transaminase (ALT, EC:2.6.1.2), asparate transaminase (AST, EC:2.6.1.1) and lactate dehydrogenase (LDH, EC: 1.1.1.27). The toxicity was further evidenced by a significant decrease of non-protein sulfhydryl(-SH) concentration, and a significant increase of lipid peroxidation measued as malondialdhyde (MDA) in the liver tissues. Administration of different doses of the TQ (4, 8, 12.5, 25 and 50 mg/Kg i.p.) did not alter the chosen biochemical parameters measured, while higher doses of TQ were lethal. The LD50 was 90.3 mg/Kg (77.9-104.7, 95% CL). Pretreatment of mice with different doses of TQ 1 h before CCl4 injection showed that the only dose of TQ that ameliorated hepatotoxicity of CCl4 was 12.5 mg/Kg i.p. as evidenced by the significant reduction of the elevated levels of serum enzymes as well as hepatic MDA content and significant increase of the hepatic nonprotein sulfhydryl(-SH) concentration. Treatment of mice with the other volatile oil constituents, p-cymene or alpha-pinene did not induce any changes in the serum ALT measured. In addition, i.p. administration of these compounds 1 h before CCl4 injection, did not protect mice against CC4-induced hepatotoxicity. The results of the present study indicate that TQ (12.5 mg/Kg, i.p.) may play an important role as antioxidant and may efficiently act as a protective agent against chemically-induced hepatic damage. In contrast, higher doses of TQ were found to induce oxidative stress leading to hepatic injury.
Mansour
M A
MA
Department of Pharmacology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Ginawi
O T
OT
El-Hadiyah
T
T
El-Khatib
A S
AS
Al-Shabanah
O A
OA
Al-Sawaf
H A
HA
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016227:Benzoquinones / Q000506:poisoning / Q000627:therapeutic use*; D000081008:Bicyclic Monoterpenes; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology* / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000517:prevention & control*; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000627:therapeutic use; D009822:Oils, Volatile / Q000506:poisoning / Q000627:therapeutic use*; D010938:Plant Oils; D013729:Terpenes / Q000627:therapeutic use; D029974:Carum
D016227:Benzoquinones; D000081008:Bicyclic Monoterpenes; D000081007:Cymenes; D039821:Monoterpenes; D009822:Oils, Volatile; D010938:Plant Oils; D013729:Terpenes; C007210:4-cymene; C104525:caraway oil; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C005451:alpha-pinene; C003466:thymoquinone