Abstract led to a particular aspect of heart necrosis,

Abstract   The experiment wereperformed in this present study to evaluate the therapeutic and the protectiveeffect of ethologic extract of rosemary (Rosmarinus officinalis) leaves againstacute toxicities in rats due to extreme high dose of paracetamol 1ml/  1000mg/ kg that led to a particular aspect of heart necrosis, congestion,vacuolation of heart muscle cells, and infiltration of inflammatory cells.

The leaves and stem of (Rosmarinus officinalis) werecollected, identified, dried, powdered and extracted by using 90% ethanol insoxhlet apparatus.  Twenty healthy albino mature malerat’s Rattus norvegicus were used in this study, were randomly divided intofour groups including group1 (control group), group 2 were given high dose ofparacetamol for 3 weeks, group 3 were given combination from high dose ofparacetamol and alcoholic extract of (rosemary officials) for 6 weeks, andgroup 4 were given rosemary extract for 3 weeks after it was given high dose ofparacetamol for 3 weeks. The histopathological result showed that the alcoholicextract of rosemary officinalis have the protection effect when used incombination with high dose of paracetamol that clear in microscopic appearanceof the heart muscle in group 3, while the histopathological result of group 4 revealedthe therapeutic effect to the alcoholic extract of rosemary officinalis and themicroscopic appearance showed the intact heart muscle.   ??????? ??????? ???????? ??????? ????? ????? ????????? ????????? ?????????? ?????? ??????? ????????????? ?? ??? ??????????????????:?????????????,????? ?????, ???? ?????, ?????  ???????          ???????? ??? ??????? ?????? ?????? ???????? ??????? ????? ????? ?????(?????????????) ???????? ???????? ?? ??????? ????? ????????????? ???? ????? 1000????/??? ?? ??? ????? ??? ????? ?? ???? ??????? ???????. ??? ??? ????? ?????? ????????? ????? ?? ??????? ???????? ?????? ??? ????????? ?????? ?????? ????????????? 90-95% ????????? ???? ?????????. ?? ??????? 20 ??? ?????? ???? ??? ???????????, ???????? ?????? ?????? ????? ????? ??? ???? ???? ???? ??????? ???????????????? ????? ???? ????? ?? ????????????? 1000 ???? /??? ?? ??? ????? ??? ??????????? ?????? ????? 3??????, ????????? ??????? ???? ???? ?????? ???????????????? ??????? ????????? ??????? ????? ????? ????? 250 ???? /??? ?? ??? ?????,????? ???????? ??????? ?? ??????? ????????? ??????? ????? ????? ????? 250 ????/??? ?? ??? ????? ?? ???? ??????? ?????? ???? 3 ?????? ??? ?? ????? ????? ??????? ????????????? ????? 3 ??????.

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????? ????? ????? ??????? ???????? 3 ?? ???????? ???? ?? ?????? ??????? ?? ??? ????? ??????? ?????????? ??????? ???? ???????? ????? ???????? ??? ??? ???????? ?? ??????? ??????? ???? ?????, ????? ???????????? ???????? ???????? 4 ?? ???????? ??? ????? ???? ?? ???????? ????? ????????????????? ????????? ????? ????? ???? ????? ?? ????? ?????? ?????? ????????????????????.  1.    Introduction       Rosemary is a constituentone of the mint family Lamiaceae, along with many otherherbs, such as basil, thyme, oregano, and lavender. The herb not only good tastesin cuisine, but that is also a good source of iron, vitamin B-6, and calcium. Habitually rosemary is the one herbs which have a wide range ofuses in popular medicine or beauty products , in addition it is used as a foodsflavor.

1Anciently herbal therapy play an important role as a traditionaland alternative medicine that is used to treat various diseases. 2  “Rosmarinus officinalis”, have avariety of anti?tumor, antioxidant, and anti?inflammatoryactivities and elevate the immune system and improve blood circulation. Manystudies have discern the rosemary extract is very rich in anti-oxidant that playan important role in equilibrium and removal the harmful of the free radical. Rosemaryleaves are used in medicine folk as an analgesic, antispasmodic, diuretic andantiepileptic agent 34.Large number of naturally compounds in plants whichinter in our food, such constituents may have a protecting favorable effect forthe body. In damaged systems one or more of the following actions lead todevilry of the tissue: (a) free radicals slink (b) cellular antioxidants altitude(c) boost for the bone marrow recovery (d) regeneration of extra hematologicaltissue which are inspire by plants or herbs may reveal the suggested principalmechanisms for protection. 5 The most important constituents of rosemary iscaffeic acid and its derivatives like rosmarinic acid (have antioxidant effect)and the phenolic compound, these constituents is well absorbed fromgastrointestinal tract and from the skin.

6R. Officinalis leaves have a wide range of bioactivities such as antitumor,antioxidant, antibacterial and anti-inflammatory actions. The bioactivities ofrosemary leaves extract are comparable with known antioxidants constituents,such as carnasol, carnosic acid, rosemarenic acid, butylated hydroxyanisole,butylated hydroxytoluene and ursolic acid, with no confederate hazard tocarcinogenicity or cyto-toxicity of the artificial antioxidants. 7, 8, 9 Paracetamolis one of the most commonly used non-steroidal anti-inflammatory drugs(NSAIDs). The heart muscle after long term and high dose of paracetamol sufferingfrom severe vacoulation in the myocardial muscle fibers as well as the severeatrophy and fibrosis especially in the pericardial region.

Myocyte cell deathby both apoptosis and necrosis has also been suggested. 10, 11 The histologicalstructure of the heart and vessels tissue from mice treated with paracetamolshowed moderate vascular congestion and inflammatory alteration like themyocytes coagulation and cardio-toxicity. 12, 13 High dose of paracetamolfor long term take the risk of reverse response, typical for selectiveinhibition of COX-2, such as hypertension, heart infarction (necrosis) or renalfailure.

14 . This study aimed to investigate the protective and therapeutic effectof Rosmarinus officinalis leave extract by ethanol alcohol on heart muscle versusthe long term of high dose of paracetamol.  2 Material and method2.1 Experiment animals      Twenty healthy albinomature male rat’s Rattus norvegicus were used in this study. Theseanimals weighing 350-450 gm ±5g.

The animals were obtained from the Animalhouse of the pharmacy collage University of Kerbela. The animals were kept at atemperature between 25-28C°. The air of the room was changed continuously byusing ventilating vacuum and light/dark cycle (12/12) hr/per/day.

The littersof cages were changed every second days. They were given a rodent dietsupplement with a Vitamin C and supplied with water ad libitum. The animalswere left in normal conditions for two weeks for acclimatization in animalhouse.2.2 Experimental design:    Twenty adult male ratswere randomly divided into four groups (5 rat/ group) and were treated daily asfollows:Group 1:   Rat of this groupwere allowed to ad libitum supply of drinking water (control group).Group 2:   Rat of this groupwere administered paracetamol 1ml 1000mg/kg.

B.Wby gavage needle.Group 3:  Rat of this groupwere administered combination paracetamol 1ml 1000mg/kg.B.W and 250 mg/kg B.

W alcoholic extract of rosemary by gavage needle.Group 4:  Rat of this groupwere administered 250 mg/kg B.W alcoholicextract of rosemary for 3weeks afteradministered by paracetamol 1ml  1000mg/kg. B.W for 3 weeks by gavage needle.2.

3 Plant materialFreshRosemary officials’leaves were collected from a local medical gardenin   pharmacy collage (Kerbela) during June. Later these plant leaves were washed under tap water, and then dried in room temperature atshade. The dried leaves were crushed by a laboratory blender. The plantclassification was done Dr. Ibraheim Saleh Abbas of the Pharmacognosydepartment, pharmacy faculty, Al-Mustansiriya University.2.

4 Extraction of plant          Extraction was carried out by using ethanol (95% ethyl alcohol) for the Rosemary officials’ leaves and stem whichis considered as a very effective in extracting the active ingredients of theplant according to method described by 15. Soxhlet apparatus was used that consists of anelectric heater with a thermostat regulator upon which a round bottom glassflask placed that fitted to an extraction unit.2.5 Experimental of Histopathology        For histopathological study the rats were anesthetized by high dose tosacrifice them.

Immediately, after sacrifice, the heart was removed andpreserved it in 10% neutral formalin buffer solution. The histological sections were stained with hematoxylin and eosin(H&E). Severaltissue sections (1cm) were prepared according to 16.The slides were examined under light microscope for the reveled thehistopathological changed. Result The histopathological study for animal treated with high dose of paracetamolfollowed by administration with rosemary extract showed the following:Group 1 :These group showed the normalhistological structure for the heart muscle (Figure 1, 2)Group 2: The cardiac muscle in these groupsuffering from degeneration and necrosis, and  there is markedly separation between themuscle fiber and vacoulation in myocardial cells, also there are presence ofglobular hemorrhage with infiltration of inflammatory cells (Figure 3, 4, 5)Group 3: The cardiac muscle showed moderatevacuolation in the myocardial muscle cells, decreased the degeneration andlittle infiltration of inflammatory cells, also there is a fibrosis inpericardial region (Figure 6, 7).

   Group 4 : In this group the heart muscle appearslike normal and intact cardiac muscle with moderated congestion of vessel. (Figure8, 9)