Review Article - Journal of Clinical and Experimental Toxicology (2018) Volume 2, Issue 2
The preventive and curative role of Nigella sativa in poisoning cases.Said Said Elshama*
Department of Forensic Medicine and Clinical Toxicology, College of Medicine, Suez Canal, University, Ismailia City, Egypt, College of Medicine, Taif University, Taif, Saudi Arabia
- *Corresponding Author:
- Said Said Elshama
Department of Forensic Medicine and Clinical Toxicology
College of Medicine Suez Canal University Ismailia City, Egypt
E-mail: [email protected]
Accepted date: August 26, 2018
Nigella sativa was used in folk medicine as a promising medicinal plant from many years ago. Therapeutic efficacy of Nigella sativa is attributed to thymoquinone that has cytoprotective action. Thymoquinone is a potent antioxidant effect via the oxidizing agents reduction and antioxidant molecules induction. A lot of studies proved that Nigella sativa has an effective preventive and curative outcome in many intoxicated cases. Most of these studies showed that Nigella sativa has the ability to prevent or cure the serious toxic manifestations of common drugs including some chemotherapeutic drugs, antibiotics, and analgesics besides some chemicals such as insecticides, organic solvents, and toxic elements.
Nigella sativa, antioxidant, prevention, curative
Folk or alternative medicine that is based on herbal plants was used a traditional treatment in many diseases for centuries in the different areas of the world especially the developing countries. Until now, it is still used in rural areas wherein 80% of the Asian and African population utilize it in primary health care. So, many studies were conducted on these medicinal plants to investigate its efficacy and safety . Nigella sativa is a marvel medicinal plant because of its wide potent therapeutic effects which were guaranteed historical and religious. Nigella sativa is called black seed among Muslim people wherein it was mentioned in the prophetic medicine as a promising medicinal plant .
Nigella sativa is one of Ranunculaceae family which grows spontaneously in the several areas of the world. This plant contains a lot of tiny dark black seeds that are used in cheese, bread, and pastry as a known spice and flavoring additive. However, it was also used in traditional medicine as a remedy for many illnesses owing to the reported therapeutic effects. The black seeds contain more than 100 bioactive molecules such as the different types of vitamins (A, B, C) and minerals (calcium, potassium, zinc, iron) besides the saturated and unsaturated fatty acids . According to many studies, the seeds of Nigella sativa and its oil have a broad range of curative effects wherein it is considered anti-hypertensive, anti-diabetic, anti-inflammatory, diuretic, analgesic, antibacterial, antiviral, anthelmintic, immunomodulator, anti-tumor and antioxidant .
The health benefits of Nigella sativa have been due to its active ingredients that are concentrated in fixed and essential oil. This oil is rich source of bioactive phytochemicals that represents 85% of the total compounds such as thymoquinone and tocopherols . Nigella sativa oil supplementation in the food products is utilized to promote the human health against common disorders such as hyperglycemia and hypercholesterolemia. The nutritional value of Nigella sativa oil is attributed to its ability to preserve the food from the degradation during processing and storage. Nigella sativa oil diminishes the microbial growth and delays the oxidation of oxidizable materials such as lipids .
Therapeutic efficacy of Nigella sativa is attributed to its essential constituent that is called thymoquinone and its derivatives which are cytoprotective agents through its potent antioxidant effect via the reduction of oxidizing agents and the induction of the cellular antioxidant molecules . From this a point of view, more attention have been paid to the use of Nigella sativa as a preventive and curative agent in the poisoning cases wherein the toxic manifestations of drugs and chemical intoxications are attributed to the oxidative stress process that produces the reactive oxygen species leading to a damage in the different cellular components and a lipid peroxidation in the various organs such as kidney, liver, and brain [8,9].
In the last years, a lot of studies were conducted on Nigella sativa using its health benefits for addressing many medical problems. So, this article endeavors to concentrate on the preventive and therapeutic role of Nigella sativa in the poisoning cases based on the available published researches.
Nigella sativa and Drug Intoxication
In the previous years, a lot of studies were carried out to investigate the efficacy of Nigella sativa in addressing the toxic manifestations that are emerging due to the use of some common medications. Cyclophosphamide is considered one of these medications that cause a known significant toxicity in the clinical field wherein induce significant alterations in the liver and renal functions, a decrease in hemoglobin concentration, an increases in the blood sugar level associated with an increase in the levels of triglyceride, cholesterol and low-density lipoprotein.
Alenzi and his colleagues  studied the preventive role of Nigella sativa in modulating the toxicity of cyclophosphamide wherein they proved the ability of Nigella sativa as an antioxidant to overcome the overall toxicity of cyclophosphamide that is resulted from the overproduction of reactive oxygen spices and the associated oxidative stress.
In the related context, Gore, et al.  showed that cyclophosphamide may induce hemorrhagic cystitis based on an increase in the oxidative stress, the inflammatory cytokines, and associated with a suppression in the activity of nuclear factor related erythroid 2-related factor (Nrf2). Furthermore, Gore and his colleagues indicated that the repeated use of cyclophosphamide over a long period may lead to bladder cancer. So, the study of Gore, et al. demonstrated the preventive effect of thymoquinone (active constituent of Nigella sativa) against cyclophosphamide-induced hemorrhagic cystitis via a reduction in the oxidative stress, inhibiting of DNA damage and upregulation of Nrf2 expression.
In the same context, Suddek, eta al.  referred that thymoquinone can attenuate cyclophosphamide-induced pulmonary injury via the restoration of antioxidant enzymes levels besides a reduction in the secretion of pro-inflammatory cytokine and lipid peroxidation in the lung tissues. In addition to, thymoquinone significantly alleviated the pulmonary histopathological changes and improved the associated serum biomarkers, and then the inflammatory reactions.
Moreover, other researches were conducted on the beneficial effects of thymoquinone as an antioxidant and anti-inflammatory to modulate the toxic effect of another chemotherapeutic agent that is cisplatin. Al-Malki and Sayed,  suggested that thymoquinone can ameliorate all toxic effects of cisplatin on the liver wherein it improves the toxic hepatic histopathological changes, attenuates the activated NF-κB in the liver, increases the antioxidant enzymes activities including glutathione peroxidase and glutathione-S transferase in the hepatic tissues, and reduces the levels of malondialdehyde . In addition, the expression and concentrations of inflammatory tumor necrosis factor, nitric oxide synthetase, and interleukin were significantly reduced improving the energy metabolism, accelerating the injured organelles regeneration, and strengthening the endogenous antioxidant defense mechanism .
On another hand, other studies showed that thymoquinone may be a renoprotective agent against cisplatin-induced nephrotoxicity  wherein thymoquinone has an ability to prevent the onset and progression of nephrotoxicity via decreasing the lipid peroxidation and increasing the activity of antioxidant enzymes in the renal tissues . Hosseinian and his colleagues  supported also the role of oxidative stress in the pathophysiology of cisplatin-induced nephrotoxicity and clarified the ability of Nigella sativa to recover the renal damage.
Likewise, Badary, et al.  demonstrated that the high antioxidant potential of thymoquinone can significantly modulate doxorubicin-induced hyperlipidemic nephropathy suppressing proteinuria and albuminuria wherein it is considered as an applicable protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome. Moreover, Alam, et al.  found that thymoquinone has a protective effect against doxorubicin-induced cardiotoxicity via accelerating the heart antioxidant defense mechanism and down-regulating the lipid peroxidation level towards the normality. Thus, thymoquinone may be utilized as a potential drug for toxic cardiomyopathy in accordance with Nagi and Mansour .
Furthermore, Nigella sativa may have cardioprotective effects according to the study of Ebru and his colleagues  who reported that its oil can lessen the cyclosporine A-induced cardiotoxicity owing to its antioxidant effect wherein the cardiac insult is a consequence of oxidative stress that is caused by the toxic effect of cyclosporine. In addition, Nigella sativa oil can abolish all toxic manifestations of cyclosporine on the heart decreasing the lipid peroxidation, improving the cellular protein oxidation, and normalizing the cardiac histopathological changes.
Over the past years, a number of researches were conducted on the protective role of Nigella sativa against paracetamolinduced hepatorenal damage that is manifested by a disturbance in the liver and renal function tests associated with the toxic hepatic and renal histopathological changes.
Hasan, et al.  confirmed the preventive role of Nigella sativa against paracetamol-induced hepatotoxicity and nephrotoxicity while Canayakin and his colleagues  showed the prophylactic role of Nigella sativa against paracetamolinduced nephrotoxicity wherein Hamza, et al.  and Adam, et al.  referred to hepatoprotective effects of Nigella sativa against acetaminophen-induced oxidative stress and hepatotoxicity. According to the results of these studies, the hepatoprotection role of Nigella sativa is attributed to the direct and indirect effects of thymoquinone wherein it is antioxidant besides enhancing the activity of other antioxidants such as glutathione, catalase, and superoxide dismutase boosting the body’s antioxidant mechanism against the oxidative stress. On another hand, the nephroprotection role of Nigella sativa is due to enhancing the prostaglandin synthesis leading to an inadequate renal perfusion besides the detoxification of the free radicals via significant improving the activities of antioxidant enzymes promoting the antioxidant mechanism.
Otherwise, Omar  pay more attention to the neuroprotective role of Nigella sativa and proved that administration of its oil can protect the cortical neurons and myelinated axons against tramadol-induced toxic changes wherein it alleviates ultrastructural apoptotic changes in the motor cerebral cortex. On another hand, Elkhateeb, et al.  indicated to the hepatoprotective and nephroprotective roles of Linn oil of Nigella sativa on hepatotoxicity and nephrotoxicity of tramadol.
Elshama, et al.  also proved that Nigella sativa can modulate the toxic testicular manifestations of the colchicine repeated use via normalization the plasma testosterone level, reducing the number of abnormal-shaped sperms, improving the sperm motility and liveability. In another context, Ali  and Rehman, et al.  showed the ability of Nigella sativa to ameliorate the renal toxic effects of gentamicin normalizing the renal biochemical parameters and the renal morphological changes.
Every day and with the scientific research development, the utilizing field of Nigella sativa in the treatment of poisoning cases is expanded to overcome the toxic side effects of other new therapeutic agents such as hypervitaminosis, oxytetracycline, isoproterenol, sodium valproate, and isoniazid.
According to Al-Suhaimi  Nigella sativa oil has a considerable hepatoprotective effect against hypervitaminosis A and a humoral immune response to vitamin A intoxication wherein it is an effective inducer of IgG and IgM in the serum with the high doses of vitamin A.
In the related context, Abdel-Daim and Ghazy  indicated to the hepatoprotective and renoprotective effect of Nigella sativa oil against oxytetracycline - induced hepatotoxicity and nephrotoxicity while Hassan, et al.  demonstrated the cardioprotective effect of Nigella sativa against isoproterenolinduced myocardial infarction via restoring the normal levels of cardiac biomarkers as well as antioxidant markers associated with modulation the cardiac histopathological changes.
Furthermore, Wahba  suggested that Nigella sativa may also protect the testicular tissues against the toxic effect of sodium valproate. In accordance with the results of the previous studies, the study of Hassan, et al.  referred also to the protective role of Nigella sativa in the hepatotoxicity of another drug that is one of the antituberculous drugs (isoniazid).
Table 1 shows a summary of the ameliorative effect of Nigella sativa on the above-mentioned drugs intoxication related to the affected organ or system.
|Drug||Affected Organ or System||Reference|
|Alenzi, et al. 
Gore, et al., 
Suddek, eta al., 
|Al-Malki, et al. 
Hosseinian, et al. 
|Badary, et al. 
Alam, et al. 
Nagi, et al. 
|Cyclosporine A||Cardiotoxicity||Ebru, et al. |
|Hasan, et al. 
Canayakin, et al. 
Hamza, et al., 
Adam, et al., 
Elkhateeb, et al. 
|Colchicine||Testicular toxicity||Elshama, et al. |
Rehman, et al. 
|Hypervitaminosis A||Hepatotoxicity||Al-Suhaimi |
|Daim, et al. |
|Isoproterenol||Cardiotoxicity||Hassan, et al. |
|Sodium Valproate||Testicular toxicity||Wahba |
|Isoniazid||Hepatotoxicity||Hassan, et al. |
Table 1. Ameliorative effect of Nigella sativa against different drugs intoxication.
Nigella sativa and Chemical Intoxication
In another context, a number of researches focused on the protective role of Nigella sativa against chemicals intoxication and conducted to the fruitful results in this field. Nagi and Almakki  showed that Nigella sativa is a promising prophylactic agent against chemical toxicity and carcinogenesis via enhancing the activities of glutathione transferase and quinone reductase. El Gendy, et al.  reported that Nigella sativa corrects the toxic biochemical disturbance which is induced by nitrosamine precursors administration wherein it ameliorates the levels of oxidative stress markers such as reduced glutathione, nitric oxide and the cancer-related genes such as bcl2, p53, and HER-2/neu.
Furthermore, Ahmad and Alkreathy  proved that the ameliorative effect of Nigella sativa against thioacetamideinduced hepatorenal toxicity wherein thioacetamide is classified as a potent centrilobular hepatotoxic agent and carcinogen of class 2B. Noteworthy, acute and chronic thioacetamide exposure leads to hepatic toxicity via interfering DNA, RNA, protein synthesis, and gamma-glutamyl transpeptidase activity by its bioactive metabolites.
In another context, Nigella sativa has an ability to counteract the toxic effect of gamma radiation on the jejunal mucosa attenuating the toxic morphological changes . It is also a promising radioprotective agent against hemopoietic, immunosuppressive, and oxidative effects of gamma irradiation toxicity .
In addition, Nagilla sativa has a protective effect against the toxicity of another inorganic chemical compound that is sodium nitrite; it is a commonly used color fixative and preservative. Thymoquinone is able to restore the normal balance between pro and anti-inflammatory cytokines and protect the renal tissue form extrinsic and intrinsic apoptosis that is attributed to the toxicity of sodium nitrite . Mansour, et al.  also demonstrated the protective effect of the volatile oil of Nigella sativa against carbon tetrachloride -induced hepatic damage as an efficient antioxidant in accordance with Krishnan and Muthukrishnan .
In the previous years, the large number of studies was carried out for the use of the protective effect of Nigella sativa in amelioration the hepatotoxicity of other toxic agents such as ethanol. Alsaif  and Develi, et al.  indicated that Nigella sativa is an effective agent in protecting the oxidative stressinduced hepatotoxicity in accordance with Hosseini, et al.  who confirmed also the protective effect of thymoquinone against ethanol-induced hepatotoxicity and nephrotoxicity together. El-Dakhakhny, et al.  conclude that Nigella sativa exerts a gastroprotective effect against ethanol-induced ulcer via a significant increase in the glutathione level, mucin content, and the free acidity associated with a significant decrease in the gastric mucosal histamine content.
Toluene is one of the aromatic hydrocarbons wherein it is used as a major solvent in numerous household products and occupational locations. Toluene Inhalation is one of the most popular forms of inhalant abuse wherein chronic toluene exposure is one of the most serious chemical toxicities. So, the toxic effects of chronic toluene exposure have been investigated extensively by the researchers to find a solution protecting the body systems such as the central nervous system and lung against its serious impact.
In the last years, more attention was paid towards this problem by Kanter who conducted some studies on chronic toluene exposure and its effects on CNS, lung, and testis by using Nigella sativa and the derived thymoquinone as a protective agent to ameliorate its toxic manifestations. Kanter showed that Nigella sativa can improve neurodegeneration in hippocampus that is caused by chronic toluene exposure . In another research, Kanter proved that Nigella sativa is able to modulate the pulmonary toxicity of toluene via inhibiting the inflammatory pulmonary responses, alveolar edema and exudate, interstitial fibrosis and necrosis besides a significant reduction in the activity of apoptosis, inducible nitric oxide synthase, and an increase in the pulmonary expression of surfactant protein D . In the third research of Kanter, Nigella sativa demonstrated an excellent efficacy in preventing the toluene-induced testicular toxicity and re-establishing the spermatogenesis via a significant reduction in the endothelial nitric oxide synthase and a rise in the expression of proliferating cell nuclear antigen in the testicular tissues .
Aluminum is another chemical toxic element and has serious hazards on human health; its oral exposure leads to hepatotoxicity, nephrotoxicity and hematological changes. Many studies used Nigella sativa to minimize the hazards of aluminum. These studies indicated to the protective effect of Nigella sativa against aluminum toxicity wherein co-administration of black seed with aluminum showed marked improvement in the hepatic and renal biochemical parameters [51,52] as well as alleviating the histopathological findings and hematological disorders .
In the different types of researches, the ameliorative action of Nigella sativa against the toxicity of other elements was proved. Parveen and Shadabig  indicated to its protective effect against iron-induced chromosomal aberrations in the bone marrow cells while Farrag, et al.  showed its preventive role against lead-induced hepatorenal toxicity. In the related context, Mohammed, et al.  referred also to the ability of Nigella sativa to attenuate cadmium-induced nephrotoxicity and neurotoxicity based on the biochemical and histological studies.
Recently, the poisoning cases of the widely used environmental chemicals such as the pesticides and insecticides become one of the most toxicological problems that face physicians in the clinical field. So, many researchers focused on their researches to find an efficient new substitute to treat or prevent the insecticides toxicity. Thus, Nigella sativa was used in many of these various studies as a new preventive agent in insecticides intoxication cases.
Suleman, et al.  indicated to the ability of the Nigella sativa oil in amelioration the hepatotoxicity induced via an exposure to the bifenthrin while Ince, et al.  reported that thymoquinone can attenuate the toxicity from the use of pyrethroid wherein it can prevent cypermethrin-induced oxidative stress and toxicity.
Propoxur is another widely used carbamate insecticide that has neurotoxic effects inducing lipid and protein peroxidation, a decrease in acetylcholine esterase activity in the brain associated with a decrease in the levels antioxidant activities and nonenzymatic antioxidant. Mohamadin, et al.  conclude that Nigella sativa significantly reduces propoxur induced toxicity and oxidative stress in the brain via a free radicals scavenging mechanism.
In the related context, Pourgholamhossein, et al.  showed that thymoquinone can alleviate the lung fibrosis induced by paraquat herbicide through the oxidative stress inhibition and pro-fibrotic genes down-regulation wherein paraquat is considered one of the highly toxic pesticides which cause a serious toxicity among humans. Furthermore, another study confirmed the protective role of Nigella sativa oil against chlorpyrifos that also is one of the most commonly used insecticides in the world. This study demonstrated that the concurrent administration of Nigella sativa oil and chlorpyrifos can reverse all manifestations of the reproductive toxicity wherein it improves the testosterone level, semen picture, antioxidant enzymes activities, and the testicular histopathological changes .
Finally, the protective effect of Nigella sativa extended to overcome the toxic effects of other chemical agents such as tartrazine that is widely used as an additive in the foods and drugs improving its taste. Al-Seenia, et al.  concluded that Nigella sativa can protect against tartrazine toxicity improving the kidney and liver functions, and other toxic manifestations on the testis and stomach. Nigella sativa can also normalize the total protein, total cholesterol, triglycerides, low and high-density lipoproteins, antioxidants activities and the lipid peroxidation in the different body tissues.
Table 2 shows a summary of the ameliorative effect of Nigella sativa on the above-mentioned toxic agents effects related to the affected organ or system.
|Toxic agent||Affected Organ or System||Reference|
|Nitrosamine||Hepatotoxicity||El Gendy, et al. |
|Gamma Radiation||Jejunal affection
|Orhon, et al. 
|Sodium Nitrite||Nephrotoxicity||Elsherbiny, et al. |
|Carbon Tetrachloride||Hepatotoxicity||Mansour, et al. 
Krishnan, et al. 
Toxic gastric ulcer
Develi, et al. 
Hosseini, et al. 
El-Dakhakhny, et al. 
|Mahdy, et al. 
Mohamed, et al. 
|Iron||Chromosomal Aberrations||Parveen, et al. |
|Farrag, et al. |
|Mohammed, et al. |
|Bifenthrin||Hepatotoxicity||Suleman, et al. |
|Pyrethroid||Oxidative toxicity||Ince, et al. |
|Propoxur||Neurotoxicity||Mohamadin, et al. |
|Paraquat||Lung fibrosis||Pourgholamhossein, et al. |
|Chlorpyrifos||Reproductive toxicity||Mosbah, et al. |
|Al-Seenia, et al. |
Table 2. Ameliorative effect of Nigella sativa against different toxic agents effects.
Nigella sativa is one of the medicinal plants that have marvel protective and therapeutic effects in a lot of the intoxicated cases. A number of studies revealed that Nigella sativa is a potent antioxidant agent and has an outstanding efficacy in preventing or treating the toxic manifestations of some common drugs and chemicals based on its oxidative stress mechanism inducing toxicity.
Further human researches should be conducted in the future to investigate the preventive and curative efficacy of Nigella sativa in the various intoxication cases.
Conflict of Interest Statement
There is no conflict of interest.
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