Toxicity of trigonella Foenum graecum (Fenugreek) In Bone Marrow Cell Proliferation in Rat.
Door: M. araee, M. Norouzi, G. Habibi en M. Sheikhvatan.
Medical Sciences/University of Tehran, Iran.
Fenugreek is a plant from the family Leguminosae cultivatied in some countries such as India
Africa, Egypt, Morocco and occasionally in England.
Feugreek is an old medicanal plant and has been commonly used as a traditional food and medicine.
The seeds are reported to have restorative and nutitive properties (Khosla et al., 1995) and its nutrient composition
is moisture, portein, fat, saponins, and dietary fibers (Ikeuchi et al. 2006)
In additon, wide range of its medicinal applications were identified and its medical use
for the treatment of inflammation, tumors, cardiovascular diseases, renal insufficiency, infections, and meatbolic disordersd
has been clear in several studies (Muralidhara et al, 1999; Petit et al., 1992; Sharma et al., 1990; Puri et al., 2002; Pandian et al 2002., ;
Tahiliani and Kar, 2003 ; Sur et al 2001; Ahmadiani et al., 2001)
It has been also shown that at the stated dose, it increases the bone marrow cell counts indicating its stimulatory
effect on blood cells especially maccrophages (Bin-Hafeez et al., 2003)
Futhermore, one of the nutritional profiles of Fenugreek seed is iron and may influence the iron absorption ( Fenugreek Trigonella Foenum-Graecum, 2008)
However, a few studies were available about the effects of Fenugreek
and its toxicity on immunomodulatory effects and haematopoietic stem cells of bone marrow.
Also the mechanisms of these effects have not been clear.
The goal of the present study was to investigate the effect of Fenugreek on fetal macroscopic diameters and microscopic bone marrow cell histological changes in its teratogenic dosages.
Decoction of Fenugreek plant
Fenugreek plant used in thes study was supplied by Tehran central market and its decoction was prepared from dry leaves.
For the measurement of teratogenic dosage of drug LD50 was calculated and it was 4.1 g/kg in female rat and 3.5 g/kg in male rat.
Fetal mortality rate was uncreased in injected drug dose (fig.1)
The results of the measurement of fetal diameters were summarized in table 1.
There was a positive relation between the increase of drug doses and decrease in the fetal ear to ear diameter, however, other fetal diameters were not dependant to the drug dosage increasing.
In histological evaluation of stem cells, no difference between the effects of distilled water and drug infection
with the dosage of 0.8 g/kg (P=0.820) and 1.6 g/kg (P=0.180) was fond, but the severity of stem cells
histological changes caused by 3.2 g/kg drug injections was lower than distilled water injection (P<0.001)
In evaluation of other cells of bone marrow (Figs. 2-5) significant differences in the severity of histological changes between three groups with different drug injection and control group was detected (table 2)
Exept for the changes in haematopotic cord, in other types of bone marrow cell, significant decrease in the severity of histological changes with the increase of drug dosages was found (tabble 2)
The toxic effects of Fenugreek on male and female reproductive system and also its adverse effects on developing fetus
have been shown in precious studies.
In a study by Kassem et al (2006) a significant reducrion in fetuses developing due to the reductions of both fetal and placental weights
at 20 days of gestation and litter size was observed.
This result was proven histopathologically by the observation of proliferative changes of the endometrial glands (Kassem et al 2006)
Similarly, in the present study, we also showed the side effects of this drug on the decrease of the fetal ear to ear diameter
and increase of fetal mortality rate.
However, the effects of Fenugreek on bone marrow proliferation and its side effects on the normal
histological pattern of bone marrow cell have nog been clearly demonstrated.
In the present study we found the side effects of high dose Fenugreek especially 3.2 g/kg dosage on the majority types of bone marrow cell.
These side effects can be occurred following to the different etiologies.
In vivo investigations on animal models showed the impairment of peripheral conversion of thyroid hormones (Kelly 2000)
Futhermore a stimulatory effect on bone marrow cellularity was observed in normal rats contimuously
infused with thyroid hormones.
Results of studies on bone marrow were expressed in absolute numbers of total nucleated erythroid cells per miligram of femoral marrow at the beginning and after 8 hours of continuous infusions (malgor et al 1972)
Therefore, differences in histological changes in bone marrow cell proliferation may be caused by the effects of Fenugreek on thyroid hormones secretion.
It has been clearly shown that the intestinal disaccharidase activity and glucose absorption can be decreased and gastrointestinal motility increased by the admmistration of a soluble dietary fiber fractionof Fenugreek.
and thus it can decrease serum glucose, increased liver glycogen content and enhanced total antioxidant status (Hannan et al 2007)
Also, Fenugreek administered at 2 and 8 g/kg dose orally significantly reduced the blood sugar both in normal and diabetic rats (Khosla et al 1995)
In addition, the metabolism of bone marrow is directly dependant to glucose (Vaccari et al 1958)
Therefore, decrease in glucose absorption in bone marrow may lead to metabolic disturbances of bone marrow cell and enzymatic dysfunction in bone marrow cell proliferation.
Is was also suggested that estrogen can regulate B lymphocyte development in mouse bone marrow and its deficiency causes a marked increase in bone marrow cel (Mansuzawa et al 1994)
The p45 NF-E2 turn on 3b-HSD gene and encodes an enzyme for regulation of all steroid hormone biosynthesis
3b-HSD induces the estogen producing in the form of estradiol, in megakaryocyte cells.
It has been shown that the addition of exogenous estradiol can increase pro-platelet, while the inhibition of estradiol receptors blocked pro-platelet in live mice ( Nagata et al 2003)
Futhermore, Fenugreek seed is a source of the steroidal saponin diosgenin.
It has been demonstrated that both progesterone and estrogen (estradiol [1,3,5 (10)-estratrien-3, 17S-diol]) levels were lower in the Fenugreek fed females as compared with those in the control animals (Kassem et al. 2006).
In view of the role of estradiol on bone marrow formation and also the precence of steroidal saponin diosgenin in Fenugreek seed, it seems that the administration of Fenugreek
in high dosages may adversely influence the bone marrow cell proloferation.
In spite of the fact that above probable mechanisms and relationships may explain the bone marrow changes after
high dose administration of Fenugreek, more studies for demonstration of these mechanisms are needed.