11.2.3 Biosafety and Toxicological Studies
Utilization of natural polymers for biomedical applications is continuously
increasing owing to their minimal cost, biocompatibility and minimal side effects. It
is of utmost importance to evaluate the probable toxic effects of these polymers
before their preclinical and clinical applications. Previous toxicological studies
affirm that seed extract/seed powder of fenugreek is non-toxic to experimental
animals at a single oral dose of 5 g/kg. Opdyke et al., showed that acute oral LD 50
of fenugreek was more than 5 g/kg in rats (Opdyke 1978) while the LD 50 for acute
dermal toxicity in rabbits was found to be 2 g/kg. Repeated dose toxicity studies for
90 days concluded that debitterized fenugreek was safe to weaning rats and no
significant toxic effects were noticed in behavioural pattern, food intake and growth
of animals (Narasimhamurthy et al. 1999). Trigonelline, an alkaloid present in the
seeds of fenugreek, was also found to be not altering the weights of mice thymus,
kidney, liver, thyroid, adrenals, uterus or ovaries when fed for three weeks. Oral
uptake of fenugreek seed extract for six months did not cause any clinical, hepatic,
renal and hematological irregularities in diabetic human patients (Sharma et al.
1996a, b). On the other hand, in a randomized, double blinded, placebo-paralleled
trial type II diabetes melitus patients suffered from stomach discomfort, nausea and
diarrhea due to subchronic administration of saponins derived from fenugreek
seeds. Patients were provided with 2.1 g of saponins thrice a day for a period of
three months (Lu et al. 2008).
Subchronic oral administration of fenugreek seed powder acts as an antifertility
agent in rodents by altering the weight of the reproductive tissues, sperm count and
morphological irregularities in sperm cells (Al-Ashban et al. 2010; Al-Yahya 2013).
Sharma and Bhinda. observed decline in weights of ovaries and uterine due to
administration of steroidal extract of fenugreek (100 mg/day/rat for 15 days) to
adult female rats (Sharma and Bhinda 2005). Elbetieha et al. (1996) suggested
fenugreek seed powder induced abnormalities in fertility of female rats due to its
estrogenic activity that distorts endothelial lining and interfaces of fetal development (Elbetieha et al. 1996).
The toxicological properties of fenugreek seed powder were observed by various
animal models and human trials. From the above observations, it was clear that
fenugreek act as antifertility agent in both male and female animals. But particular
molecule and cellular mechanism responsible for antifertility of fenugreek is still in
debate. Further investigations are needed to identify the compositional element of
fenugreek seed, which acts as toxic agent. Toxico-metabolomics and metabolic flux
analysis experiments may be helpful to understand the cellular metabolism and
detoxification pathways (Table 11.2).
386
P. Mishra et al.
Utilization of natural polymers for biomedical applications is continuously
increasing owing to their minimal cost, biocompatibility and minimal side effects. It
is of utmost importance to evaluate the probable toxic effects of these polymers
before their preclinical and clinical applications. Previous toxicological studies
affirm that seed extract/seed powder of fenugreek is non-toxic to experimental
animals at a single oral dose of 5 g/kg. Opdyke et al., showed that acute oral LD 50
of fenugreek was more than 5 g/kg in rats (Opdyke 1978) while the LD 50 for acute
dermal toxicity in rabbits was found to be 2 g/kg. Repeated dose toxicity studies for
90 days concluded that debitterized fenugreek was safe to weaning rats and no
significant toxic effects were noticed in behavioural pattern, food intake and growth
of animals (Narasimhamurthy et al. 1999). Trigonelline, an alkaloid present in the
seeds of fenugreek, was also found to be not altering the weights of mice thymus,
kidney, liver, thyroid, adrenals, uterus or ovaries when fed for three weeks. Oral
uptake of fenugreek seed extract for six months did not cause any clinical, hepatic,
renal and hematological irregularities in diabetic human patients (Sharma et al.
1996a, b). On the other hand, in a randomized, double blinded, placebo-paralleled
trial type II diabetes melitus patients suffered from stomach discomfort, nausea and
diarrhea due to subchronic administration of saponins derived from fenugreek
seeds. Patients were provided with 2.1 g of saponins thrice a day for a period of
three months (Lu et al. 2008).
Subchronic oral administration of fenugreek seed powder acts as an antifertility
agent in rodents by altering the weight of the reproductive tissues, sperm count and
morphological irregularities in sperm cells (Al-Ashban et al. 2010; Al-Yahya 2013).
Sharma and Bhinda. observed decline in weights of ovaries and uterine due to
administration of steroidal extract of fenugreek (100 mg/day/rat for 15 days) to
adult female rats (Sharma and Bhinda 2005). Elbetieha et al. (1996) suggested
fenugreek seed powder induced abnormalities in fertility of female rats due to its
estrogenic activity that distorts endothelial lining and interfaces of fetal development (Elbetieha et al. 1996).
The toxicological properties of fenugreek seed powder were observed by various
animal models and human trials. From the above observations, it was clear that
fenugreek act as antifertility agent in both male and female animals. But particular
molecule and cellular mechanism responsible for antifertility of fenugreek is still in
debate. Further investigations are needed to identify the compositional element of
fenugreek seed, which acts as toxic agent. Toxico-metabolomics and metabolic flux
analysis experiments may be helpful to understand the cellular metabolism and
detoxification pathways (Table 11.2).
386
P. Mishra et al.