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| ORIGINAL ARTICLE |
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| Year : 2019 | Volume
: 8
| Issue : 1 | Page : 21-27 |
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Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae): Acute and sub-acute toxicity studies in Wistar rats
Abdulhakim Abubakar1, Abdullahi Balarabe Nazifi2, Fatima Ismail Hassan3, Kehinde Andem Duke1, Theophillus Danjuma Edoh1
1 Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria
2 Department of Pharmacology and Therapeutics, Bayero University, Kano, Nigeria
3 Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria, Nigeria; Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| Date of Submission | 28-Oct-2018 |
| Date of Decision | 04-Dec-2018 |
| Date of Acceptance | 28-Dec-2018 |
| Date of Web Publication | 24-Jan-2019 |
Correspondence Address:
Abdulhakim Abubakar
Department of Pharmacology and Therapeutics, Ahmadu Bello University, Zaria
Nigeria
 Source of Support: None, Conflict of Interest: None  | 8 |
DOI: 10.4103/2221-6189.250374
Objective: To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5 000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5 000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/ body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.
Keywords: Chlorophytum alismifolium, Toxicity studies, Biochemical parameters, Histology
How to cite this article:
Abubakar A, Nazifi AB, Hassan FI, Duke KA, Edoh TD. Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae): Acute and sub-acute toxicity studies in Wistar rats. J Acute Dis 2019;8:21-7 |
How to cite this URL:
Abubakar A, Nazifi AB, Hassan FI, Duke KA, Edoh TD. Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae): Acute and sub-acute toxicity studies in Wistar rats. J Acute Dis [serial online] 2019 [cited 2023 Mar 22];8:21-7. Available from: https://www.jadweb.org/text.asp?2019/8/1/21/250374 |
| 1. Introduction | |  |
The utilization of plants and their resources for combating various diseases has been known since antiquity and they are still in use worldwide[1]. Plants constitute important source of drugs[2] and according to the statistics of World Health Organization, many inhabitants of developing countries rely on natural products from plants as medications for various ailments[3]. Herbal preparations are complementary medicines for the remedy of many diseases due to their presumed appropriateness, safety, efficacy and affordability[4]. In the past, herbal medicine has drawn remarkable interests for many studies[5], and as a justification, more investigations are conducted on medicinal plants and their constituents in order to explore their toxicity potentials, because they produce a wide range of drugs of therapeutic benefit[6],[7]. Therefore, it should be a fundamental requirement to establish the harmful consequences of some of the phyto-constituents[8] and this could be achieved through toxicological studies in experimental animals[9]. Information of toxicity studies on medicinal plants or their constituents should be obtained in order to guarantee assurances in their safety to humans[10]. Thus, it is imperative to evaluate the potential toxic effects or safety profile of any medicinal plant intended to be used in animals or humans.
The genus Chlorophytum (Liliaceae) covers about 198 species of important medicinal plants broadly distributed in the tropical regions of the world, notably in India and Africa[11]. Chlorophytum alismifolium (C. alismifolium) (Baker), is a short stem herb that is found around stony sites in forest streams containing white flowers and tuberous root stocks[12]. The common name is Alimsa-ground lilly while the local names include Rogon Makwarwa, Ekuce, and Cigorodi in “Hausa”, “Agatu” and “Fufulde” languages respectively. It is extensively utilized in herbal medicine against nociception and diabetes mellitus. The antinociceptive, anti-inflammatory and anti- hyperglycaemic activities of the tubers have been reported[13],[14]. Despite the widespread folk uses and pharmacological effects of C. alismifolium, little is known about its safety. Assessment of the toxicity profile of phyto-constituents is a vital requirement in order to assure their safety[15]. Furthermore, the increasing awareness in herbal medicine necessitates toxicity studies on products derived from medicinal plants[16]. Thus, this study intended to investigate the effects of C. alismifolium following 28 d repeated daily administration in rats.
| 2. Materials and methods | | |
2.1. Animals
Wistar rats of either sex (100-140)g were sourced from experimental animal facility of the Faculty of Pharmaceutical Sciences, Ahmadu Bello University (A.B.U.), Zaria, Nigeria. They were managed in well-ventilated cages at room temperature under normal day and night cycle, kept on pelletized animal feed (Vital feed®, Jos) with access to water ad libitum. The animals were treated in accordance with the NIH Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, revised, 1996) and approved by institutional Research and Ethical Committee (Protocol Number: DAC/IW-OT/212-15).
2.2. Plant material
Fresh tubers of C. alismifolium were obtained in June, 2017 from Toro, Bauchi State, Nigeria. It was identified and authenticated in the Herbarium of the Department of Botany, A.B.U., Zaria, by Namadi Sanusi. A voucher number of 6 785 was issued by comparing with a previously deposited voucher specimen.
2.3. Plant extraction
The fresh tubers obtained were size-reduced and dried before pulverization into powder with the aid of a mortar and pestle. Two kilograms (2 kg) of the powdered plant was extracted using soxhlet apparatus with 5 L of methanol and water (in the proportion of 9:1 respectively) for 3 d. The extract obtained was subsequently concentrated over a water bath set at a temperature of 50 °C. The dried extract was weighed and labeled as methanol extract of C. alismifolium (MECA). It was kept in a desiccator at room temperature [(25±1.5) C] and protected from light until further use.
2.4. Phytochemical screening
MECA was subjected to qualitative phytochemical tests as described by Evans[17] to screen for the presence or absence of secondary metabolites.
2.5. Preparation of extract and treatment
Different stock solutions of MECA were prepared using distilled water followed by serial dilution to obtain the final experimental concentrations. The solutions were freshly prepared daily and orally administered with the aid of oral gavages.
2.6. Acute toxicity studies
The median lethal dose (LD50) of MECA was determined in accordance with the Organization for Economic Co-operation and Development (OECD, 425) guidelines[18] using five rats which were fasted overnight before dosing with MECA at 5 000 mg/kg orally. One rat was initially dosed and food was further withheld for 4 h. It was observed for the first 24 h and then for 14 d for signs of toxicity (changes in mucous membranes, skin, fur and eyes, circulatory, respiratory, somato-motor activity and behaviour pattern) and mortality. The remaining four rats were also dosed and observed for 2 weeks. Thereafter, the LD50 was estimated.
2.7. Sub-acute toxicity studies
The study was conducted according to OECD 407 guidelines[19]. Briefly, twenty four rats were fasted overnight and then divided into four groups of six rats each. The first group of rats served as control and received distilled water 1 mL/kg. The 2nd, 3rd and 4th group were administered graded doses of MECA (150 mg/kg, 300 mg/kg and 600 mg/kg body weight respectively) daily for 28 d. The mortality and general behaviour of the rats were observed daily and their weights were recorded weekly. The rats were then euthanized on the 29th day of the experiment following mild chloroform anaesthesia. Their organs and blood samples were collected for further investigations.
2.8. Haematological indices evaluation
Blood samples for haematological evaluation were collected into ethylene diamine tetra-acetic acid containing sample bottles to prevent coagulation. Thereafter, the levels of white blood cells, lymphocytes, granulocytes, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, packed cell volume and platelets were estimated using haematology machine (Cell-Dyn, Abbott, USA).
2.9. Evaluation of biochemical parameters and electrolytes
Plain bottles were used to collect blood samples, allowed to clot and then centrifuged at 3 500 rpm for 10 min. The serums obtained were investigated to estimate the effect of MECA on biochemical indices using photoelectric colorimeter (AC-115 Optima, Japan). The parameters estimated were alanine amino transferase (ALT) and aspartate amino transferase (AST)[20], alkaline phosphatase (ALP)[21], total bilirubin[22], total protein, albumin and globulin[23], urea[24] and creatinine[25]. The effect of the extract on electrolytes (potassium, sodium, bicarbonate and chloride) was also determined with the aid of Hitachi 902 analyzer (Roche, Germany).
2.10. Evaluation of organ-body weight ratio
The kidneys, livers, pancreases and hearts of the rats were removed on the 29th day following blood collection and were cropped to remove other tissues. The organs were then placed on a saline soaked gauze and then weighed (with paired organs weighed together). The relative organ-body weight ratio was then evaluated using the relationship:
2.11. Histology
The kidneys and livers were stabled for 10 d using formaldehyde (10%). They were then dehydrated, cleared and infiltrated with paraffin wax. Thereafter, they were embedded before sectioning. With the aid of a microtome, 5 μm sections of the organs were made, placed on a slide and stained with haematoxylin and eosin. The stained sections were finally viewed under a microscope for morphological changes[26].
2.12. Statistical analyses
Data generated from the experiments were entered into SPSS software (Version 20). Descriptive statistics was carried out to obtain the mean ± SEM. Data on relative organ body weight, haematological, hepatic and renal indices were analyzed by one way analysis of variance (ANOVA) while those on body weight were analyzed using repeated measure ANOVA and Bonferroni test for comparison over time. Statistical significant differences were considered at 95% confidence interval (P<0.05).
| 3. Results | | |
3.1. Extractive value and phytochemical constituents
The MECA obtained was gummy in nature with a honey-like aroma. The extraction of 2 000 g of the powdered plant material produced 104.2 g of the extract corresponding to the yield of 5.21 %(w/w). Screening for phytochemical constituents showed the presence of flavonoids, alkaloids, triterpenes, saponins, glycosides and cardiac glycosides.
3.2. Effect of acute administration of MECA on general behaviour and mortality
The oral administration of MECA produced no visible signs of toxicity and mortality throughout the study period. The LD50 was thus found to be above 5 000 mg/kg.
3.3. Effect of 28-days daily administration of MECA on general behaviour and mortality
Oral administration of MECA (150 mg/kg, 300 mg/kg and 600 mg/kg) did not induce any mortality. There were also no observable changes in behaviour throughout the study period when compared to the control group.
3.4. Effect of 28-days daily administration of MECA on body weights
The administration of MECA did not produce significant (P>0.05) changes in the body weights of the rats when compared to control group. However, a significant (P<0.01) increase in the body weights was observed at 150 mg/kg in the fourth week compared to the first week. Similarly, a significant increase (P<0.05 and P<0.01) was observed at 600 mg/kg in weeks three and four respectively [Figure 1]; [Table 1]. | Figure 1: Effect of 28 d daily administration of methanol extract of C. alismifolium on body weights of rats. Values are presented as mean ± SEM; *: P<0.05; **: P<0.01 compared to week 1-Repeated measure ANOVA followed by Bonferroni post hoc test, n=6; D/W: Distilled water.
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3.5. Effect of 28-days daily administration of MECA on relative organ-body weights
The administration of MECA did not produce a significant (P>0.05) increase or decrease in the relative organ/body weights as compared to control group [Table 2]. | Table 2: Effect of 28 d oral administration of MECA on relative organ body weights of rats.
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3.6. Effect of 28-days daily administration of MECA on haematological parameters
Administration of MECA produced no significant (P>0.05) changes in the tested haematological parameters as compared to control group [Table 3]. | Table 3: Effect of 28 d administration of MECA on haematological parameters in rats.
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3.7. Effect of 28-days daily administration of MECA on hepatic indices
Administration of C. alismifolium extract did not produce significant (P>0.05) changes in the liver enzymes, total bilirubin and proteins as compared to control group [Table 4]. | Table 4: Effect of 28 d administration of MECA on hepatic indices in rats.
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3.8. Effect of 28-days daily administration of MECA on renal indices
Administration of C. alismifolium extract did not produce significant (P>0.05) changes in the levels of urea, creatinine and serum electrolytes as compared to control group [Table 5]. | Table 5: Effect of 28 d oral administration of MECA on renal indices and electrolytes in rats.
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3.9. Effects of 28-days daily administration of MECA on histology of the kidneys and livers
Histological examination of the kidneys revealed slight adhesion in the glomerulus and distortion of the tubules at 150 mg/kg of the extract. Slight glomerular distortion and lymphocyte hyperplasia were observed at 300 mg/kg and 600 mg/kg respectively [Figure 2]. Moderate hepatic necrosis was observed with the doses of 150 mg/kg and 300 mg/kg respectively, however, there were no histopathological changes in the hepatocytes at 600 mg/kg [Figure 3]. | Figure 2: Photomicrograph of the kidney sections of rats administered distilled water and MECA for 28 d. A: Distilled water treated group showing normal tubules (black arrow) and glomerulus (red arrow). B: MECA 150 mg/kg treated group showing moderate tubular adhesion. C: MECA 300 mg/kg treated group showing slight glomerular distortion (black arrow) and moderate tubular adhesion (red arrow). D: MECA 600 mg/kg treated group showing slight lymphocyte hyperplasia (black arrow) and slight tubular distortion (red arrow). (H and E, magnification ×250).
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 | Figure 3: Photomicrograph of the liver sections of rats administered distilled water and MECA for 28 d. A: Distilled water treated group showing normal hepatocytes. B: MECA 150 mg/kg treated group showing moderate vacoulations and necrosis. C: MECA 300 mg/kg treated group showing moderate hepatic necrosis (blue arrow). D: MECA 600 mg/kg treated group showing normal hepatocytes. (H and E, magnification ×250).
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| 4. Discussion | | |
The use of herbal medicines as a source of drugs has gained wide acceptability globally, especially in low and middle-income countries[27]. Medicinal plants are known for containing varying pharmacologically active constituents[28]. Although these plants may elicit numerous pharmacological activities, much is unknown about their potential to cause toxicity. Acute toxicity studies on C. alismifolium extract showed that it is practically non-toxic in rats following oral administration. This finding is corroborative with previous studies on the plant extract[13],[14]. The tubers of C. alismifolium have also been reported to possess bioactive compounds which could be beneficial in hyperglycaemic, painful and inflammatory conditions[13],[14]. Some of these bioactive constituents like phenolic compounds are phytochemical antioxidants with potentials for inhibiting reactive oxygen species implicated in the pathogenesis of many diseases and toxicities[29]. Despite these therapeutic benefits, there are no reports on its toxicological profile following repeated administration. This study therefore presents useful information on the sub-acute toxicity profile of C. alismifolium tuber extract.
Variation in body weights is an indication of toxic effects of chemicals[30],[31]. In this research, administration of C. alismifolium extract did not reduce the body weights of the animals suggesting that it did not exert any deteriorative effect on their growth. Furthermore, the significant increase in the body weights over time showed that MECA did not impair feed utilization of the rats. Similarly, the extract did not alter the organ weights of the rats and could therefore be considered non-toxic because reductions in the weights are sensitive markers of toxicity[32].
The haematopoietic system is a susceptible target for toxic compounds, especially in the bone marrow where the production of red blood cells occurs[33]. Haematological indices are commonly used markers of toxicity as a result of the interaction between a toxin and its potential metabolites on cellular components[34]. In this research, administration of graded doses of MECA did not cause significant changes on the haematological indices when compared with control group, thus, suggesting that it may be non- toxic to the blood system.
The liver and kidneys are crucial organs that perform significant role in detoxification[35]. The main organ for xenobiotics metabolism is the liver where compounds or hepatotoxic metabolites may be formed[36]. An increase in the levels of liver enzymes (AST, ALT and ALP) is conventionally an indication of liver injury[37]. Administration of graded doses of tuber extract of C. alismifolium did not produce major effects on the serum levels of liver enzymes, bilirubin and proteins in the experimental animals when compared with control. This indicates that the functions of the liver is not affected by the extract after 28 d treatment. Creatinine and urea are regarded as important markers of renal malfunction[38] and are used in diagnosing kidneys’ function or monitor clinical outcome of a therapy[39]. In this research, the lack of substantial changes in these parameters and serum electrolytes is a suggestion that C. alismifolium tuber extract has no harmful effect on the kidneys.
No marked changes were observed in the histo-morphology of organs following 28 d oral administration of C. alismifolium. However, slight to moderate histopathological alterations were observed in the liver and kidneys of rats in the extract treated groups. Considering the liver, levels of ALT and AST which are the major indicators of liver injury were not significantly altered. Therefore, these changes may not be significant toxicologically, since they were not supported by some of the findings from biochemical analysis.
The results obtained showed that C. alismifolium tuber extract is practically non-toxic after acute administration and produced low toxicity after 28 d repeated administration. The MECA did not elicit systemic toxicity, however, slight to moderate histo- morphological changes were observed in the kidneys and liver. Therefore, there is need to conduct chronic toxicity studies in order to ascertain its long term effects.
Conflict of interest statement
The authors report no conflict of interest statement.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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