Short-term effects of oral administration of Pistacia lentiscus oil on tissue-specific toxicity and drug metabolizing enzymes in mice.
BACKGROUND
Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro.


METHODS
Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days.


RESULTS
Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation) of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues.


CONCLUSIONS
These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in combination with other pharmacological agents in order to avoid potential drug-drug interaction leading to toxicity. This study will help in safer use of Pistacia lentiscus oil for therapeutic purpose.
Department of Pharmacology and Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Samir
S
Attoub
Sherif M
SM
Karam
Abderrahim
A
Nemmar
Kholoud
K
Arafat
Annie
A
John
Wafa
W
Al-Dhaheri
Mahmood Ahmed
MA
Al Sultan
Haider
H
Raza
D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005638:Fruit / Q000737:chemistry; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009928:Organ Specificity / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D027927:Pistacia / Q000737:chemistry*; D010938:Plant Oils / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations; D010938:Plant Oils; D003577:Cytochrome P-450 Enzyme System