Natural Products and Tissue Repair: Identification, Relevance and ApplicabilityView this Special Issue
Research Article | Open Access
Navid Omidifar, Amir Nili-Ahmadabadi, Ahmad Gholami, Dara Dastan, Davoud Ahmadimoghaddam, Hossein Nili-Ahmadabadi, "Biochemical and Histological Evidence on the Protective Effects of Allium hirtifolium Boiss (Persian Shallot) as an Herbal Supplement in Cadmium-Induced Hepatotoxicity", Evidence-Based Complementary and Alternative Medicine, vol. 2020, Article ID 7457504, 8 pages, 2020. https://doi.org/10.1155/2020/7457504
Biochemical and Histological Evidence on the Protective Effects of Allium hirtifolium Boiss (Persian Shallot) as an Herbal Supplement in Cadmium-Induced Hepatotoxicity
Background and Objectives. Allium hirtifolium Boiss (Persian shallot), as an edible vegetable, has several pharmacological properties including antimicrobial, anti-inflammatory, and antioxidative effects, while its protective effects in liver cells are controversial. In this study, we examined the effect of A. hirtifolium extract on cadmium- (Cd-) induced hepatotoxicity in rats. Materials and Methods. Thirty-six male Wistar rats were divided into six groups: groups 1, 2, and 3 received vehicle, Cd (100 mg/L/day by drinking water), and A. hirtifolium extract (200 mg/kg/day; orally), respectively. Groups 4, 5, and 6 were Cd groups which were treated with A. hirtifolium extract (50, 100, and 200 mg/kg/day, respectively). After 2 weeks, liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) and also oxidative stress biomarkers including lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol molecule (TTM), and the histopathological changes were determined using standard procedure. Results. The findings showed that Cd caused a remarkable rise in levels of serum hepatic enzymes such as ALT (), AST () and ALP () compared with the control group. In addition, Cd led to the decreasing of the levels of TTM () and TAC () and increasing of LPO () in liver tissue in comparison with the control group. In this regard, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of Cd-treated rats. Following the administration of A. hirtifolium extract, a significant improvement was observed in the functional and oxidative stress indices of hepatic tissue alongside histopathologic changes. Conclusion. The current study indicated that the A. hirtifolium extract might prevent hepatic oxidative injury by improving oxidant/antioxidant balance in rats exposed to Cd.
Allium hirtifolium Boiss, known as Persian shallot “Mooseer,” grows wild as blackish, paper-like tunics in some areas of Iran and other Asian countries. It is traditionally used in the routine diet in countries of central Asia as a spice and flavoring agent in food, especially yoghurt. Recent research has suggested that A. hirtifolium is composed of 9-hexadecenoic acid, 11,14-eicosadienoic acid, and n-hexadecanoic acid, and its hydromethanolic extract has strong antimicrobial properties against several bacteria . Allicin (diallyl thiosulfinate) is considered responsible for the antibacterial, antifungal, and antiparasite potentials of A. hirtifolium . In addition to the antimicrobial property, the phenolic compound of the ethanol extract of A. hirtifolium is reported to have moderate to good antioxidant activity [3, 4], as well as immunomodulatory activity  and accelerates wound healing by increasing the epithelialization rate . The active compound of A. hirtifolium, shallomin, is also found safe in humans; therefore, research is continued on the various effects of A. hirtifolium in different organs .
Special attention has been paid to the effect of A. hirtifolium on liver protection in animal studies. A. hirtifolium extract has shown protective effects against liver cell apoptosis by inhibiting the growth of human hepatoma cancer cells and BCL2 gene . Also, the chloroformic extract of A. hirtifolium is found to be able to inhibit proliferation of tumor cell lines including cervical cancer, breast, adenocarcinoma, and connective cell lines . Hydroalcoholic extract of A. hirtifolium can also protect rat liver cells against the effects of oxidants in alloxan-induced diabetes and reduce the serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) [10, 11]. The favorable result of the hydroalchoholic extract of A. hirtifolium on reducing the serum blood glucose levels, glucokinase activity, and gene expression has also been suggested by other researchers . Nevertheless, in another study, it has been shown that A. hirtifolium extract could not decrease serum levels of apo-lipoproteins, AST, ALT, glucose, or insulin, while it could significantly reduce serum levels of triglyceride and cholesterol as well as atherosclerotic plaque thickness to media . Accordingly, the efficacy of A. hirtifolium on liver enzymes is controversial, and further research is required in this regard.
Cadmium (Cd) is a food contaminant that increases the incidence rate of liver disease [14, 15] and induces oxidative stress in different body organs, especially liver, kidney, and blood, by generating reactive oxygen species (ROS) and impairing the antioxidant defense system . Accordingly, this metal is used to induce liver failure in different animals . Therefore, the aim of the study was to evaluate the therapeutic potential of A. hirtifolium in Cd-induced hepatotoxicity in rats.
2. Materials and Methods
2.1. Preparation of the Extract
The bulbs of the A. hirtifolium were collected from Hamadan in western Iran. The plant was identified by the herbarium section of School of Pharmacy, Hamadan University of Medical Sciences (HUMS), Hamadan, Iran, with code number 234. The bulbs were ground and extracted by methanol/water (50 : 50) at 25°C for 48 h in triplicate using a maceration method. Then, the extract was filtrated and evaporated to become dry in a rotary evaporator (Heidolph, Germany) under vacuum at 40°C. The resulting extract was kept in a dark place at 4°C.
2.2. Phytochemical Screening
The phytochemical analyses were performed on the A. hirtifolium extract using the standard methods to identify secondary metabolites such as alkaloids, saponins, tannins, flavonoids, steroids, terpenoids, proteins, amino acids, glycosides, and anthraquinones [18, 19].
2.3. Determination of Total Phenolic Content
The total phenolic content of the A. hirtifolium extract was determined according to the Folin–Ciocalteu procedure, 2 hours and 1, 7, and 14 days after the extraction (each experiment was performed in triplicate). The results were expressed as mg gallic acid equivalents (GAE)/g extract .
2.4. Determination of Total Flavonoid Content
Total flavonoid content of the A. hirtifolium extract was determined based on the method reported by Fathollahi et al. , 2 hours and 1, 7, and 14 days after the extraction (each experiment was performed in triplicate). The results were expressed as mg quercetin/g extract .
2.5. Animals and Experimental Design
Thirty-six adult male Wistar rats, weighted 210–240 g, were obtained from the animal house of Hamadan University of Medical Sciences (HUMS), kept in polypropylene cages at room temperature (25 ± 2°C), 12 h dark/12 h light cycle, and humidity of about 50%, and provided with free food and water.
After one week of acclimatization, the animals were divided randomly into six groups and treated as follows: Group 1: the rats received normal saline (control group) Group 2: the rats received 100 mg/L/day Cd chloride (Cd group) Group 3: the rats received 200 mg/kg A. hirtifolium extract, orally (AhB200) Group 4: the rats received 100 mg/L/day Cd chloride by drinking water + 50 mg/kg A. hirtifolium extract orally (AhB50 + Cd) Group 5: the rats received 100 mg/L/day Cd chloride by drinking water + 100 mg/kg A. hirtifolium extract orally (AhB100 + Cd) Group 6: the rats received 100 mg/L/day Cd chloride by drinking water + 200 mg/kg A. hirtifolium extract orally (AhB200 + Cd)
After 2 weeks of treating animals of the six groups as described above, the animals were anaesthetized by 50 mg/kg ketamine and 10 mg/kg xylazine. The serum samples, obtained by centrifugation of the heart’s blood for 15 min at 5000 rpm, were kept at −20°C. A section of the fresh liver was separated and stored at −80°C for biochemical analysis. A part of rat’s liver was excised and put in 10% formalin for histological analysis.
2.6. Liver Function Experiments
The serum samples were used for examination of ALT, AST, and ALP using colorimetric biochemical kits (Pars Azmon, Iran).
2.7. Preparation of Hepatic Tissue Homogenate
The hepatic tissue (100 mg) was homogenized with 1 mL phosphate-buffered saline (50 mM, pH 7.3) and centrifuged at 3000 g for 10 min at 4°C. The supernatant was separated for the biochemical analysis .
2.8. Measurement of Lipid Peroxidation
The hepatic lipid peroxidation (LPO) was evaluated by determining bioactive aldehydes using the thiobarbituric acid reactive substances (TBARS) method . In brief, 100 µl of hepatic tissue homogenate was mixed with 500 µl reagent containing 2-thiobarbituric acid (TBA, 0.2%) in H2SO4 (0.05 M). The mixture was heated for 30 min at 100°C in boiling water bath. Then, the optimum absorbance was measured at 532 nm against different concentrations of malondialdehyde (MDA) as the standard, and its findings were reported as nmol/mg protein.
2.9. Measurement of Total Antioxidant Capacity
The total antioxidant capacity of tissue homogenate was measured by determining its ability to reduce Fe+3 to Fe+2 using the ferric-reducing antioxidant power (FRAP) method . In brief, FRAP reagent was prepared by mixing 1 volume of 20 mM FeCl3, 10 volumes of 300 mM acetate buffer (pH 3.6), and also 1 volume of 10 mM 2,4,6-tripyridyl-s-triazine (TPTZ) in 40 mM HCL. The complex between Fe2+ and TPTZ, as an indicator, gives a blue color with an absorbance maximum at 593 nm. The results were presented as nmol/mg protein.
2.10. Measurement of Total Thiol Molecules
Total thiol molecules (TTM) were assayed using 5,5′dithiobis-2-nitro benzoic acid (DTNB) as the reagent, and its absorbance was read against a blank at 412 nm . 200 µl of tris-EDTA buffer solution (0.25 M tris base and 20 mM EDTA, pH 8.2) was mixed with 10 µl of homogenized tissue, and its optimum absorbance was detected at 412 nm. Then, 10 µl of DTNB solution (10 mmol/l in methanol) was added to each sample and incubated at 37°C for 15 min. The absorbance of the samples (A2) and also DTNB blank (B) was read again at 412 nm. The level of thiol molecules was determined by reduced glutathione as standard and reported as µM/mg protein.
2.11. Protein Assay
At the end of each experiment, protein levels were measured in the crude homogenate of hepatic tissues by Bradford method.
2.12. Histopathologic Examination
After fixation of hepatic tissue in formalin (10%), the paraffin-embedded block was prepared and cut into 4 µm thick sections using a rotary microtome. The samples were stained with hematoxylin and eosin (H&E) dye for histopathological examination.
2.13. Statistical Analysis
All variables were quantitative. The mean values with standard error mean (SEM) were reported for each variable and compared among the six study groups using one-way ANOVA with Tukey’s post hoc test. For the statistical analysis, the GraphPad Prism statistical software version 6.0 was used. values <0.05 were considered statistically significant.
3.1. Phytochemical Analysis
Using the phytochemical screening, we obtained that the hydroalcoholic extract of the A. hirtifolium is composed of different compounds such as phenols, flavonoids, saponins, glycosides, steroids, tannins, terpenoids, and amino acids (Table 1). The total phenolic and flavonoid contents of A. hirtifolium extract were 80.1 ± 0.9 mg GAE/g extract and 58.2 ± 0.4 mg quercetin/g extract, respectively. During the 14 days after the extraction, no significant changes were observed in the phenolic and flavonoid values, which could indicate the stability of extract during this period (data not shown).
Strongly positive (+++), moderately positive (++), slightly positive (+), and negative (−).
3.2. The Effects of A. hirtifolium Extract on Liver Function
The results of comparing liver enzymes among the six study groups are shown in Figure 1. As illustrated, ALT, AST, and ALP levels of the Cd group were significantly higher than the control group (, , and , respectively). The two pretreatment groups, receiving 100 and 200 mg A. hirtifolium extract, had a significantly lower ALT level compared with the Cd group (). The A. hirtifolium extract could significantly decrease the serum levels of AST and ALP at the dose of 200 mg/kg, compared with the Cd group ().
3.3. The Effects of A. hirtifolium Extract on Hepatic Oxidative Damage
The results of comparing oxidative stress biomarkers among the six study groups are shown in Figure 2. As illustrated, the Cd group had a significantly higher LPO and lower TAC and TTM than the control group (). The two treatment groups, receiving 100 and 200 mg A. hirtifolium extract, had a significantly lower LPO level, compared with the Cd group (). The A. hirtifolium extract could significantly decrease the hepatic LPO level () and increase TTM levels () at the doses of 100 and 200 mg/kg, compared with the Cd group (). In addition, a significant increase was observed in the hepatic TAC levels at the dose of 200 mg/kg ().
3.4. The Effects of A. hirtifolium Extract on Pathological Changes
As mentioned in Figure 3, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of Cd-treated rats. Following the pretreatment with different doses of A. hirtifolium extract, a remarkable improvement was found in some of the pathological alterations such as vascular congestion and hepatocellular degeneration. The optimum protective effect was observed at the dose of 200 mg/kg of the extract.
The results of this study emphasize the nutritional importance of A. hirtifolium Boiss in Cd-induced liver failure. Preliminary phytochemical studies showed significant amounts of phenolic and flavonoid compounds in the A. hirtifolium extract. Due to the remarkable antioxidant properties of these compounds, quantitative contents of phenols and flavonoids were determined in the extract. Based on the received dosage range of the A. hirtifolium extract for each animal (50–200 mg/kg/day), the minimum and maximum amounts received for phenolic compounds (4–16 mg/kg/day) and flavonoid compounds (2.5–10 mg/kg/day) were estimated.
In the present study, increased hepatic serum enzymes (ALT, AST, and ALP) are considered as an important biomarker in the diagnosis of liver failure . Therefore, the results of the current study indicate disruption of hepatic cells’ integrity caused by Cd and occurrence of hepatic failure. Several animal studies have also suggested increased levels of hepatic enzymes in the rats’ serum that received Cd chloride in drinking water [27, 28], which confirm the results of the present study and emphasize on the importance of exposure to Cd. Clinical studies have also confirmed the significance of hepatotoxicity induced by Cd, which is present in soil, water, food (dietary intake), and air (smoking and air pollution), and considered an important health concern [15, 29–31]. Other studies have also shown the positive correlation of serum Cd concentrations with liver enzyme levels (ALT, AST, and ALP) in Korean adults  and Indonesian pregnant women , which is consistent with this study. According to the evidence, the body has a limited capacity to Cd exposure, and the long-term exposure to Cd accumulates Cd and causes toxicity in several organs, such as liver and kidneys and impair their function [34–36], indicating the toxic effect of Cd in different organ systems .
Since oxidative stress plays a fundamental role in Cd-induced hepatic failure, the oxidant/antioxidant markers were evaluated in this survey. In the current study, a significant increase in LPO and a noticeable decrease in TTM and TAC liver levels were found in the Cd group, indicating the induction of oxidative damage due to Cd toxicity. Although the accurate mechanism of the increased oxidative stress is still not well understood, review studies have indicated that Cd increases the LPO by changing the intracellular glutathione levels, induces the production of ROS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inhibits antioxidants [38, 39], which are consistent with the results of the present study.
Due to the significance of oxidative damage caused by Cd, researchers have studied several herbal medicines that can protect against the destructive effects of Cd in the liver with a great focus on oxidative stress [40, 41]. However, none of previous studies have studied the protective effects of A. hirtifolium extract on Cd-induced hepatotoxicity.
Another important finding of the present study, considered the main objective of our study, was the effect of A. hirtifolium on oxidative damage induced by cadmium. Our findings indicated that A. hirtifolium could improve hepatic oxidative damage by increasing the hepatic thiol group and, subsequently, decrease liver LPO. In this regard, the previous studies have suggested that administration of some Allium species such as A. tripedale and A. jesdianum can prevent the effects of hepatotoxic agents such as acetaminophen in rats [42, 43]. A. hirtifolium is reported to have the highest antioxidant property, compared with other 12 plant extracts, as well as significant radical scavenging property . This plant and other garlic compounds have a high concentration of sulphur compounds (such as diallyl sulfide, S-ethylcysteine, diallyl disulfide, and N-acetylcysteine) with a strong antioxidant activity that protect against cell injury . A. hirtifolium is also reported to have a high concentration of saponins, sulphur-containing compounds, and flavonoids which are responsible for its antioxidant activity . Apparently, the different compositions of the plant extract, obtained from different parts of the country, can cause different degrees of antioxidative and liver-protective effects . In addition, the methanolic extract of A. hirtifolium is reported to have a higher concentration of polyphenolic, flavonoid, and proanthocyanidin compounds and a stronger antioxidative property than its aqueous extract . Therefore, the essential components of A. hirtifolium are important factors in determining its protective effects.
In conclusion, the present study showed that Cd induced significant liver injury and oxidative stress in rats, and oral administration of 100 and 200 mg A. hirtifolium extract could significantly reduce the destructive effect of Cd on the liver. Due to the fact that Iranians frequently use A. hirtifolium in combination with yoghurt, it would be of great importance if such a study has been performed in humans with liver dysfunction.
The data supporting the findings of this study are available within the article.
The animal experiments were approved by the Ethics Committee of SUMS, Shiraz, Iran, with Grant no. 99-01-121-22558, in accordance with the guidelines of the Research Ethics Committee of the Ministry of Health and Medical Education, Iran (2019), based on the Helsinki Protocol (Helsinki, Finland, 1975).
Conflicts of Interest
The authors declare no conflicts of interest.
The authors would like to thankfully acknowledge the financial support from the Shiraz University of Medical Sciences (SUMS) and scientific support from HUMS.
- S. Ismail, F. A. Jalilian, A. H. Talebpour et al., “Chemical composition and antibacterial and cytotoxic activities of Allium hirtifolium Boiss,” BioMed research international, vol. 2013, Article ID 696835, 8 pages, 2013.
- J. Asgarpanah and B. Ghanizadeh, “Pharmacologic and medicinal properties of Allium hirtifolium Boiss,” African Journal of Pharmacy and Pharmacology, vol. 6, no. 25, pp. 1809–1814, 2012.
- H. Ghahremani-majd, F. Dashti, D. Dastan, H. Mumivand, J. Hadian, and M. Esna-Ashari, “Antioxidant and antimicrobial activities of Iranian mooseer (Allium hirtifolium Boiss) populations,” Horticulture, Environment, and Biotechnology, vol. 53, no. 2, pp. 116–122, 2012.
- A. G. Pirbalouti, Y. Ahmadzadeh, and F. Malekpoor, “Variation in antioxidant, and antibacterial activities and total phenolic content of the bulbs of mooseer (Allium hirtifolium Boiss),” Acta Agriculturae Slovenica, vol. 105, no. 1, pp. 15–22, 2015.
- A. Jafarian, A. Ghannadi, and A. Elyasi, “The effects of Allium hirtifolium Boiss on cell-mediated immune response in mice,” Iranian Journal of Pharmaceutical Research, vol. 2, no. 1, pp. 51–55, 2010.
- H. Ghodrati Azadi, B. Fathi, H. Kazemi Mehrjerdi, M. Maleki, H. Shaterzadeh, and M. Abyazi, “Macroscopic evaluation of wound healing activity of the Persian shallot, Allium hirtifolium in rat,” Iranian Journal of Veterinary Science and Technology, vol. 3, no. 1, pp. 31–38, 2012.
- M. Amin, M. H. Pipelzadeh, M. Mehdinejad, and I. Rashidi, “An in vivo toxicological study upon shallomin, the active antimicrobial constitute of Persian shallot (Allium hirtifolium Boiss) extract,” Jundishapur Journal of Natural Pharmaceutical Products, vol. 7, no. 1, pp. 17–21, 2012.
- F. S. Hosseini, S. K. Falahati-Pour, M. R. Hajizadeh et al., “Persian shallot, Allium hirtifolium Boiss, induced apoptosis in human hepatocellular carcinoma cells,” Cytotechnology, vol. 69, no. 4, pp. 551–563, 2017.
- H. G. Azadi, S. M. Ghaffari, G. H. Riazi, S. Ahmadian, and F. Vahedi, “Antiproliferative activity of chloroformic extract of Persian shallot, Allium hirtifolium, on tumor cell lines,” Cytotechnology, vol. 56, no. 3, pp. 179–185, 2008.
- H. Javad, H.-Z. Seyed-Mostafa, O. Farhad et al., “Hepatoprotective effects of hydroalcoholic extract of Allium Hirtifolium (Persian shallot) in diabetic rats,” Journal of Basic and Clinical Physiology and Pharmacology, vol. 2, no. 1, 2012.
- S. Kazemi, S. Asgary, J. Moshtaghian, M. Rafieian, A. Adelnia, and F. Shamsi, “Liver-protective effects of hydroalcoholic extract of Allium hirtifolium boiss in rats with alloxan-induced diabetes mellitus,” Arya Atherosclerosis, vol. 6, no. 1, pp. 11–5, 2010.
- M. Mahmoodi, S. Zarei, M. Rezaeian et al., “Persian shallot (<>Allium hirtifolium<> boiss) extract elevates glucokinase (GCK) activity and gene expression in diabetic rats,” American Journal of Plant Sciences, vol. 4, no. 7, pp. 1393–1399, 2013.
- M. Rafieian-Kopaei, M. Keshvari, S. Asgary, M. Salimi, and E. Heidarian, “Potential role of a nutraceutical spice (Allium hirtifolium) in reduction of atherosclerotic plaques,” Journal of HerbMed Pharmacology, vol. 2, 2013.
- A. Heshmati, J. Karami-Momtaz, A. Nili-Ahmadabadi, and S. Ghadimi, “Dietary exposure to toxic and essential trace elements by consumption of wild and farmed carp (Cyprinus carpio) and Caspian kutum (Rutilus frisii kutum) in Iran,” Chemosphere, vol. 173, pp. 207–215, 2017.
- O. Hyder, M. Chung, D. Cosgrove et al., “Cadmium exposure and liver disease among US adults,” Journal of Gastrointestinal Surgery, vol. 17, no. 7, pp. 1265–1273, 2013.
- V. Matović, A. Buha, D. Ðukić-Ćosić, and Z. Bulat, “Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys,” Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, vol. 78, pp. 130–140, 2015.
- J. Renugadevi and S. M. Prabu, “Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin,” Experimental and Toxicologic Pathology, vol. 62, no. 2, pp. 171–181, 2010.
- R. kumar Bargah, “Preliminary test of phytochemical screening of crude ethanolic and aqueous extract of Moringa pterygosperma Gaertn,” Journal of Pharmacognosy and Phytochemistry, vol. 4, no. 1, 2015.
- S. C. Ugochukwu, A. Uche, and O. Ifeanyi, “Preliminary phytochemical screening of different solvent extracts of stem bark and roots of Dennetia tripetala G. Baker,” Asian Journal of Plant Science and Research, vol. 3, no. 3, pp. 10–13, 2013.
- D. Dastan, P. Salehi, and H. Maroofi, “Chemical composition, antioxidant, and antimicrobial activities onLaserpitium carduchorumHedge&LamondEssential oil and extracts during various growing stages,” Chemistry & Biodiversity, vol. 13, no. 10, pp. 1397–1403, 2016.
- R. Fathollahi, D. Dastan, J. Lari, and S. Masoudi, “Chemical composition, antimicrobial and antioxidant activities of Crupina crupinastrum as a medicinal plant growing wild in west of Iran,” Journal of Reports in Pharmaceutical Sciences, vol. 7, no. 2, pp. 174–182, 2018.
- H. Zeinvand-Lorestani, A. Nili-Ahmadabadi, F. Balak, G. Hasanzadeh, and O. Sabzevari, “Protective role of thymoquinone against paraquat-induced hepatotoxicity in mice,” Pesticide Biochemistry and Physiology, vol. 148, pp. 16–21, 2018.
- H. Ohkawa, N. Ohishi, and K. Yagi, “Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction,” Analytical Biochemistry, vol. 95, no. 2, pp. 351–358, 1979.
- I. F. F. Benzie and J. J. Strain, “The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay,” Analytical Biochemistry, vol. 239, no. 1, pp. 70–76, 1996.
- M.-L. Hu, “Measurement of protein thiol groups and glutathione in plasma,” Methods in Enzymology, vol. 233, pp. 380–385, 1994.
- A. Nili-Ahmadabadi, P. Alibolandi, A. Ranjbar et al., “Thymoquinone attenuates hepatotoxicity and oxidative damage caused by diazinon: an in vivo study,” Research in Pharmaceutical Sciences, vol. 13, no. 6, p. 500, 2018.
- I. Alhazzi, “Cadmium induced hepatotoxicity and oxidative stress in rats: protection by selenium,” Research Journal of Environmental Sciences, vol. 2, no. 4, pp. 305–309, 2008.
- S. Asagba and G. Eriyamremu, “Oral cadmium exposure alters haematological and liver function parameters of rats fed a Nigerian‐like diet,” Journal of Nutritional & Environmental Medicine, vol. 16, no. 3-4, pp. 267–274, 2007.
- J. I. Anetor, O. Osibanjo, H. Benedo Osadolor, F. A Idomeh, W. Osazee Igiewe, and O. Uzoma Kalikwu, “Liver damage risk assessment study in workers occupationally exposed to E-waste in Benin city, south-south Nigeria,” Journal of Chemical Health Risks, vol. 5, no. 3, 2015.
- S. Sand and W. Becker, “Assessment of dietary cadmium exposure in Sweden and population health concern including scenario analysis,” Food and Chemical Toxicology, vol. 50, no. 3-4, pp. 536–544, 2012.
- S. Satarug, D. A. Vesey, and G. C. Gobe, “Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe?” Environmental Health Perspectives, vol. 125, no. 3, pp. 284–288, 2017.
- M.-Y. Kang, S.-H. Cho, Y.-H. Lim, J.-C. Seo, and Y.-C. Hong, “Effects of environmental cadmium exposure on liver function in adults,” Occupational and Environmental Medicine, vol. 70, no. 4, pp. 268–273, 2013.
- A. Wibowo, F. A. Rahaju, E. Iskandar, and E. Suhartono, “The role of urinary cadmium on liver function and erythrocytes cell count in pregnancy,” International Journal of Bioscience, Biochemistry and Bioinformatics, vol. 4, no. 4, pp. 224–228, 2014.
- D. Dastan, S. Karimi, A. Larki-Harchegani, and A. Nili-Ahmadabadi, “Protective effects of Allium hirtifolium Boiss extract on cadmium-induced renal failure in rats,” Environmental Science and Pollution Research, vol. 23, no. 18, pp. 18886–18892, 2019.
- A. Sarkar, G. Ravindran, and V. Krishnamurthy, “A brief review on the effect of cadmium toxicity: from cellular to organ level,” International Journal of Biotechnology Research, vol. 3, no. 1, pp. 17–36, 2013.
- A. Wallia, N. B. Allen, S. Badon, and M. El Muayed, “Association between urinary cadmium levels and prediabetes in the NHANES 2005-2010 population,” International Journal of Hygiene and Environmental Health, vol. 217, no. 8, pp. 854–860, 2014.
- V. Arroyo, K. Flores, L. Ortiz, L. Gómez-Quiroz, and M. Gutiérrez-Ruiz, “Liver and cadmium toxicity,” Journal of Drug Metabolism and Toxicology, vol. 5, no. 1, 2012.
- A. Cuypers, M. Plusquin, T. Remans et al., “Cadmium stress: an oxidative challenge,” Biometals, vol. 23, no. 5, pp. 927–940, 2010.
- R. Patra, A. K. Rautray, and D. Swarup, “Oxidative stress in lead and cadmium toxicity and its amelioration,” Veterinary Medicine International, vol. 2011, Article ID 457327, 9 pages, 2011.
- S. Andleeb, S. Shaukat, and C. Ara, “Protection against cadmium-induced abnormalities and hepatotoxicity in ovo by Allium sativum,” Punjab University Journal of Zoology, vol. 33, no. 1, pp. 34–41, 2018.
- U. E. Obioha, S. M. Suru, K. F. Ola-Mudathir, and T. Y. Faremi, “Hepatoprotective potentials of onion and garlic extracts on cadmium-induced oxidative damage in rats,” Biological Trace Element Research, vol. 129, no. 1-3, p. 143, 2009.
- S. Ghobadi, D. Dastan, M. Soleimani, and A. Nili-Ahmadabadi, “Hepatoprotective potential and antioxidant activity of Allium tripedale in acetaminophen-induced oxidative damage,” Research in Pharmaceutical Sciences, vol. 14, no. 6, p. 488, 2019.
- Z. Sohrabinezhad, D. Dastan, S. S. Asl, and A. Nili-Ahmadabadi, “Allium jesdianum extract improve acetaminophen-induced hepatic failure through inhibition of oxidative/nitrosative stress,” Journal of Pharmacopuncture, vol. 22, no. 4, p. 239, 2019.
- E. Souri, G. R. AMIN, H. Jalalizadeh, and S. Barezi, “Screening of Thirteen Medicinal Plant Extracts for Antioxidant Activity,” Life Sciences, vol. 73, no. 2, pp. 167–179, 2008.
- S. H. Omar and N. A. Al-Wabel, “Organosulfur compounds and possible mechanism of garlic in cancer,” Saudi Pharmaceutical Journal, vol. 18, no. 1, pp. 51–58, 2010.
- N. Hajian, Z. Rezayatmand, and K. Shahanipur, “Preventive effects of Allium hirtifolium Boiss methanolic and aqueous extracts on renal injury induced by lead in rats,” Journal of HerbMed Pharmacology, vol. 7, no. 3, 2018.
- A. Siahpoosh and S. Souhangir, “Antioxidative and free radical scavenging activities of aqueous and methanolic bulbs extracts of Allium hirtifolium,” International Journal of Biosciences, vol. 5, no. 9, pp. 379–392, 2014.
Copyright © 2020 Navid Omidifar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.