الفهرس 
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Abstract
Methotrexate, a folic acid analogue and antagonist, is widely used as a cytotoxic chemotherapeutic agent in the treatment of malignancies and some autoimmune diseases, but the efficacy is limited due to its side effects. The cytotoxic effect of MTX is not selective for cancer and hyperproliferative cells, it affects the normal tissues as well. The amount of the damage and its severity is based on the duration and amount of drug used to treat the disease (37).
Green Tea contains various components with health-promoting effects. It is believed to have protective effects against diseases such as cancer, diabetes, obesity, hepatitis and neurodegenerative diseases. Majority of scientific evi-dence based on cellular and animal experiments as well as a number of human epidemiological and intervention studies demonstrate that Green Tea has beneficial health effects against various diseases (10).
Black Seed, an annual Ranunculaceae herbaceous plant, has been used for centuries in the Middle East and India. It has been shown that Black Seed as well as thymoquinone (TQ) as its active constituent, inhibit lipid peroxidation in liposomes and have appreciable free radical scavenging properties (8).
This study was conducted to evaluate and compare the effect of Green Tea extract and Black Seed oil on Methotrexate induced oral mucositis and submandibular salivary gland cytotoxicity in Albino rats.
Fifty six, 10-12 weeks old male Albino rats, weighing 200 to 250 grams were used in the experiment. The Albino rats were randomly divided into 4 groups, 14 rats in each group. Each group was subdivided into 2 subgroups : in the first subgroup the duration of the experiment was 5 days (A), and in the second subgroup the duration of the experiment was 10 days (B). The first group was the control group which had intraperitoneal injection of saline only on the first day of the experiment and distilled water was administered orally by orogastric tube daily. The second group was (MTX treated group) which had MTX (20 mg\kg) intraperitoneal injection on the first day of the experiment (one single dose) and distilled water was administered orally by orogastric tube daily. The third group was (MTX + Green Tea treated group) which had MTX (20 mg\kg) intraperitoneal injection on the first day of the experiment (one single dose) and Green Tea extract (20 mg\kg) was given orally by orogastric tube two times daily (total 40 mg\ kg\day). The fourth group was (MTX + Black Seed treated group) which had MTX (20 mg\kg) intraperitoneal injection on the first day of the experiment (one single dose) and Black seed oil (1 gm\kg) was given orally by orogastric tube once daily. Sacrifice of rats was done at the end of 5 and 10 days.
The specimens taken at each time interval were immediately fixed in 10% formalin for 24 hours. Washing was done in tap water then serial ascending concentration of alcohol were used for dehydration. Specimens were cleared in xylene for 2 hours to be cleaned from the remaining alcohol. Specimens were then embedded in paraffin blocks, for sectioning at 5 micron thickness. The obtained tissue sections were collected on glass slides, deparaffinized, stained by hematoxylin and eosin (H and E) stain, PAS stain and COX-2 marker for histological, histochemical and immunohistochemical examination.
Our results in submandibular salivary gland revealed normal acinar and ductal structure in control group, while in MTX treated groups after 5 and 10 days there was ductal dilatation and structural damage. After treatment with Green Tea and Black Seed, there was an improvement in the structure of the salivary gland.
In buccal mucosa and dorsum of tongue, epithelial hyperplasia, hyper keratosis and signs of inflammation were noticed after injection of MTX, while the groups treated with Green Tea and Black Seed partially restored its structural integrity.
Our results in submandibular salivary gland revealed protective effect of Black Seed at 5 and 10 days. While Green Tea had protective effect at 10 days only.
In buccal mucosa, Green Tea at 5 and 10 days had protective effect against MTX induced cytotoxicity. Black Seed had no protective effect against MTX induced cytotoxicity.
In dorsum of tongue, Green Tea at 5 and 10 days had protective effect against MTX induced cytotoxicity. Black Seed had protective effect at 5 days only.