Protection by Nigella sativa against carbon tetrachloride-induced downregulation of hepatic cytochrome P450 isozymes in rats.
Nigella sativa (family Ranunculaceae) is an annual plant that has been traditionally used on the Indian subcontinent and in Middle Eastern countries. In this study, we investigated the effect of N. sativa oil on the drug-metabolizing cytochrome P450 (CYP) enzymes and whether it has a protective effect against the acute hepatotoxicity of CCl4. Intraperitoneal injection of rats with CCl4 drastically decreased CYP2E1, CYP2B, CYP3A2, CYP2C11, and CYP1A2 mRNA and protein expressions. Oral administration of 1 ml/kg N. sativa oil every day for one week prior to CCl4 injection alleviated CCl4-induced suppression of CYP2B, CYP3A2, CYP2C11, and CYP1A2. Moreover, CCl4 increased iNOS and TNFalpha mRNA, while N. sativa oil administration for one week prior to CCl4 injection downregulated the CCl4-induced iNOS mRNA and up-regulated IL-10 mRNA. These results indicate that N. sativa oil administration has a protective effect against the CCl4-mediated suppression of hepatic CYPs and that this protective effect is partly due to the downregulation of NO production and up-regulation of the anti-inflammatory IL-10.
Ibrahim
Zein S
ZS
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Ishizuka
Mayumi
M
Soliman
Mohamed
M
ElBohi
Khlood
K
Sobhy
Wageh
W
Muzandu
Kaampwe
K
Elkattawy
Azza M
AM
Sakamoto
Kentaro Q
KQ
Fujita
Shoichi
S
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D031881:Nigella sativa / Q000737:chemistry*; D008517:Phytotherapy; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats
D007527:Isoenzymes; D010938:Plant Oils; D016753:Interleukin-10; D003577:Cytochrome P-450 Enzyme System