Effects of Teratogenic Drugs on CYP1A1 Activity in Differentiating Rat Embryo Cells.

CYP1A1, a P450 isoenzyme, is involved in the phase I xenobiotic metabolism including teratogen drugs. In the present study, the ability of teratogens to elevate the embryonic expression of CYP1A1 was examined. Micromass cell cultures prepared from day 13 rat embryo limb buds (LB). LB cells were cultivated and exposed for 5 days to retinoic acid (RA), hydrocortisone (HC), caffeine (CA) and quinine (QN). CYP1A1 protein expression and activity were measured using immunofluorescence staining and ethoxyresorufin O-deethylation (EROD) assay, respectively. The EROD activity increased significantly following LB cells exposure to RA and HC (p<0.05) but the expression of CYP1A1 protein was reduced by these drugs, whereas the expression of CYP1A1 protein and EROD activity decreased significantly following the addition of CA and QN (p<0.05, p<0.01). Our findings show that studied teratogens have potency to increase CYP1A1 activity.

Protective effect of pretreatment with thymoquinone against Aflatoxin B(1) induced liver toxicity in mice.

BACKGROUND AND THE PURPOSE OF THE STUDY: Thymoquinone (TQ) is one of the active components of Nigella sativa. The plant has been used in herbal medicine for treatment of many diseases including liver complications. The present study aimed to investigate protective effects of TQ on Aflatoxin B(1) (AFB(1)) induced liver toxicity in mice. METHODS: Animals were divided into six groups and treated intraperitoneally. Group 1 (blank) served as vehicle, group 2 (positive control) received AFB(1), Group 3 was treated with 9 mg/kg of TQ, Groups 4, 5 and 6 were treated with 4.5, 9 and 18 mg/kg of TQ, respectively. After three consecutive days, except for groups 1 and 3, animals were administered with a single dose of AFB(1) (2 mg/kg). All the animals were killed 24 hrs following the AFB(1) administration under ether anesthesia. Biochemical parameters including AST, ALT and ALP in serum samples and glutathione (GSH) and malondialdehyde (MDA) contents in liver homogenates were determined. Liver sections were collected for histopathological examination. RESULTS: Findings of this study showed that AST, ALT, ALP and MDA levels were significantly lower in the TQ treated animals as compared to AFB(1) group (group 2). Furthermore, TQ was able to recover glutathione content (GSH) of liver tissue. The best response, however, was observed with the dose of 9 mg/kg. Liver sections of AFB(1) intoxicated mice showed inflammation, necrosis, hyperplasia of kupffer and infiltration of mononuclear cells, dilation of sinusoids and disruption of hepatocytes, while treatment with TQ helped to normalize liver architecture in accordance to biochemical findings. CONCLUSION: Taken collectively, TQ has a protective role with optimum dose of 9 mg/kg in AFB(1) hepatotoxicity.