Nitrogen dioxide poisoning | |
---|---|
Specialty | Emergency medicine |
Nitrogen dioxide poisoning is the illness resulting from the toxic effect of Nitrogen (II) oxide. It usually occurs after the inhalation of the gas beyond the threshold limit value. [1] Nitrogen (II) oxide is reddish-brown with very a sharp, harsh smell at high concentrations. It is colourless and odourless at lower concentration but yet harmful. Nitrogen dioxide poisoning depends on the duration, frequency and intensity of exposure. Nitrogen (II) oxide is an irritant of the mucous membrane linked with other air pollutant that causes pulmonary diseases such as OLD, asthma, Chronic obstructive pulmonary disease and sometimes Acute exacerbation of COPD and in fatal cases, deaths.[2] Its poor solubility in water enhances its passage and its ability to pass through the moist oral mucosa of the respiratory tract. Like most toxic gases, the dose inhaled determines the toxicity on the respiratory tract. Occupational exposures constitute the highest risk of toxicity and domestic exposure is uncommon. Prolonged exposure to low concentration of the gas may have lethal effects, as can short-term exposure to high concentrations like Chlorine gas poisoning. It is one of the major air pollutant capable of causing severe heath hazards such as Coronary artery disease as well as Stroke.[3] Nitrogen (II) oxide is often released into the environment as a byproduct of fuel combustion but rarely released by Spontaneous combustion. Known sources of Nitrogen gas poisoning includes automobile exhaust, Power stations, The toxicity may also results from non-combustible sources such as the one released from anaerobic fermentation of food grains and Anaerobic digestion of Biodegradable waste.[4] The WHO developed a global recommendation limiting exposures less than 20 part per billion for chronic exposure and value less 100ppb for one hour for acute exposure, using Nitrogen (II)oxide as a marker for other pollutant from fuel combustions.[5] The standardss also based on the concentation of Nitrogen (II) oxide that show a significant and profound effects on the function of the pulmonary of asthmatic patients.[6] Historically, some states in the U.S including Chicago and L.A have high levels of Nitrogen (II) oxide but the EPA set a standard values less than 100 ppb for one hour exposure and less than 53 ppb for chronic exposure.[7][8]
Signs and symptoms
Nitrogen gas poisoning only causes severe damage to the pulmonary artery and respiratory tract. Nitrogen (II) oxide poisoning is not harmful to all forms of life just like "Chlorine gas poisoning" and Carbon (I) oxide. It is easily absorbed through the lungs and its inhalation result in heart failure and sometimes death in severe and fatal cases.[9] Individual and races may differ in Nitrogen (II)oxide tolerance level and individual tolerance level for the gas may be altered by several factors, such as metabolic rate, barometric pressure and hematological disorders but significant exposure may result in fatal conditions that could lead to shorter life span due to heart failure.[10]
Acute poisoning
Exposure to high level of Nitrogen (II) oxide may lead to inflammation of the mucous membrane and the lower and upper respiratory tracts.[11] The symptoms of acute Nitrogen (II)oxide poisoning is non-specific and have a semblance with "ammonia gas poisoning", "chlorine gas poisoning" and carbon (I) poisoning. The symptoms also resembles that of pneumonia or viral infection and other inhalational injuries but common symptoms includes Rhinitis wheezing or coughing, conjunctivitis, headache, throat irritation and dyspnea which may progress to nasal fissures, ulcerations, or perforation.[12] The patient is usually ill-appearing, and presents with hypoxemia coupled with shallow rapid breathing. Therapy is supportive and includes removal from further Nitrogen (II) oxide exposure Systemic symptoms include fever and anorexia. Electrocardiography and Chest radiography can help in revealing diffuse, bilateral alveolar infiltrates. The Chest radiography may be used in diagnosis and the baseline could be established with a Pulmonary function testing.[13][14] There is no specific laboratory diagnostic test for acute Nitrogen dioxide poisoning but analysis of arterial blood gas level, Methemoglobin level, Complete blood count, Glucose test, Lactate threshold measurement and r peripheral blood smear may be helpful in the diagnosis of Nitrogen (II) oxide poisoning.[15] The determination of Nitrogen (II)oxide in urine or tissue does not establish the diagnosis, and there are technical and interpretive problems with these tests.[16]
Chronic poisoning
Prolong exposure to a very high level of Nitrogen (II) oxide in micro meter-size range, may have an inflammatory effect that principally targets the respiratory tracts leading to chronic Nitrogen dioxide poisoning which can occur within a days or weeks after the threshold limit value is excessively exceeded.[17] This condition causes fever, rapid breathing coupled with rapid heart rate, Fever and Severe Seizure of breath. Other effects includes: Diaphoresis, chest pain and persistent dry cough, all of which may result in weight loss, anorexia and may also lead to right-side heart enlargement and heart disease in advanced cases. Prolong exposure to relatively low levels of Nitrogen (II) oxide may cause persistent headaches and nausea.[18] Like chlorine gas poisoning, symptoms usually resolve themselves upon removal from further Nitrogen (II)oxide exposure, unless there had been an episode of severe acute poisoning.[19] Treatment and management varies with symptoms. Patients are often observed for hypoxemia for a minimum of 12 hours if there is no initial symptoms and if patient is hypoxemic, oxygen may be administer but high-dose steroids are recommended for patients with pulmonary manifestations. Patients may also be hospitalize for 12 to 24 hours or longer for observation if gaseous exchange is impared. In a case where gaseous exchange is impaired, mechanical ventilation and Intubation may be necessary and if Bronchiolitis obliterans develop within 2 to 6 weeks of Nitrogen (II) oxide exposure, corticosteroid therapy such as anticholinergic may be required for 6 to 12 months to lower the body overreaction to Nitrogen gas.[20]
Pathophysiology
Nitrogen dioxide sparingly soluble in water and on inhalation, it diffuses into the lung and slowlly hydrolyzes to Nitrious and Nitric acid which causes pulmonary edema and pneumonitis leading to the inflammation of the bronchioles and Pulmonary alveolus resulting from Lipid peroxidation as well as Oxidative stress.[21] Mucous membrane is primarily affected alongside with Type I pneumocyte and the Respiratory epithelium. The generation of free radicals from lipid peroxidation result in irritation of the bronchioles and alveoli that causes rapid destruction to the respiratory epithelial cells. The overall reaction result in the release of fluids that causes pulmonary edema.[22] Nitrogen (II) oxides poisoning may alter macrophage activity aand immune function leading to susceptibility of the body to wide range of infections and overexposure to the gas may also leads to Methemoglobinemia, a disorder characterized by a higher than normal level of methemoglobin (metHb, i.e., ferric [Fe3+] rather than ferrous [Fe2+] haemoglobin) in the blood. Methemoglobinemia prevent the binding of oxygen to haemoglobin causing oxygen depletion that could leads to severe hypoxia.[23] If Nitrogen dioxide poisoning is untreated, fibrous granulation tissue is likely to develop within the alveolar duct, a tiny ducts that connect the respiratory bronchioles to alveolar sacs, each of which contains a collection of alveoli (small mucus-lined pouches made of flattened epithelial cells). The overall reaction may cause an Obstructive lung disease. Meanwhle proliferative bronchiolitis is a secondary effect of nitrogen (II)oxide poisoning.[24]
Etiology
Occupational exposures constitute the highest risk of toxicity and its often high for farmers especially those that deals with food grains. It is equally high for firefighters, military personnel especially those officers that deals in explosives. The risk is also high for arc welders, traffic officers, aerospace staffs and miners as well as those people whose occupation are connected with the Nitric acid.[25] Silo-filler's disease is a consequence of exposure to Nitrogen (II) oxide poisoning by farmers dealing with silos. Food grains such as corn and millet as well as grasses, such as alfalfa and some other plant material produces Nitrogen dioxide within hours due to anaerobic fermentation.[26] The thresold concentrations of Nitrogen (II)oxide are often attained within 1 to 2 days, and begin to declined gradually after 10 to 14 days but if the silos is well sealed, the gas may remain in the there for weeks. Heavily fertilized Silage, particularly the ones produced from immature plants generate a higher concentrations of the gas within the silo.[27] Nitrogen dioxide is about 1.5 times heavier than air and during silage storage, Nitrogen dioxide remain in the silage material. Improper ventilation may result in exposure during the leveling of the silage.[28]
Epidemiology
The EPA have some regulations and guidelines for monitoring Nitrogen (II) oxide level, although historically, some states in the U.S including Chicago, Northeast corridor and L.A have high levels of Nitrogen (II)oxide. In 2006, the WHO estimated that over 2 million death result annually from air pollution in which Nitrogen (II) oxide constitute one of the pollutant. While over 50% of the disease that results from these pollutant are common in developing countries and the effects in developed countries is not negligible either.[29] EPA survey in the U.S suggests that 16 percent of United State's housing units are sited close to airport and highway railroad increasing the exposure risk of approximately 48 million Americans. A feasibility study of the Ozone formed from the oxidation of Nitrogen (II) oxide in ambient air reported by the WHO suggested that daily deaths of 1 to 2% is attributed to exposure to ozone concentration above 47.3 ppb and exposure above 75.7ppb is attributed to 3 to 5% increase in daily mortality. Level above 114 ppb were attributed to 5 to 9% increase daily mortality. Silo filler's disease is pervasive during the harvest seasons of food grains.[30]
On May 2015, the National Green Tribunal directed Delhi and other states in India to ban diesel vehicles that are over 10 years old as a measure to reduces Nitrogen (II) oxide emission that may result in Nitrogen (II) poisoning.[31] In 2008, the report of United Kingdom committee on the medical effects of air pollutants (COMEAP) suggested that air pollution is the cause of about 29, 000 deaths in UK.[32] The WHO urban air quality database estimated Delhi's mean annual PM 10 levels in 2010 as 286 μg /m³ and London as 23 μg /m³. In 2014, the database estimated Delhi's annual mean PM 2.5 particulate matter levels in 2013 as 156 μg /m³ whereas, London have only 8 μg /m³ in 2010 but the Nitrogen (II) oxide in London breach the European Union's standard.[33] In 2013, the annual mean Nitrogen (II) oxide levels in London was estimated as 58 μg /m³ but the save and "threshold limit value" is 40 μg /m³.[34] On March 2015, Brussels dragged the United Kingdom into court for breaching emissions limits of Nitrogen dioxide at its coal-fired Aberthaw power stations in Wales. The plant operated under a permit allowing emissions of 0.0012 μg /m³ which is more than twice the 0.000 5μg /m³ limit set out in the EU’s large combustion plant directive.[35]
Prognosis
Generally, long-term prognosis is helpful to survival of initial exposure to Nitrogen (II)oxide. Some cases of Nitrogen (II)oxide poisoning resolves with no observable symptoms and patient may be determine with pulmonary function testing.[36] If chronic exposure causes lungs damage, it could take several days or months for the pulmonary function to improve. Meanwhile permanent mild dysfunction may result from bronchiolitis obliterans and could manifests as abnormal flow at 50 to 70 percent of vital capacity. It may also manifests as mild hyperinfamation, airway obstruction and in that case, patient may be subject to steroid treatment to treat deconditioning.[37] Complications from prolong exposure includes bronchiolitis obliterans and other secondary infections such as pneumonia due to injuries on the mucous membrain from pulmonary edema and inhibition of immune system by Nitrogen (II) oxide.[38] Nitrogen dioxide result in short and long-term morbidity or death depending on the extent of exposure and inhaled concentration and the exposure time Illness resulting from acute exposure is usually not fatal although some exposure may cause bronchiolitis obliterans, pulmonary edema as well as rapid asphyxiation.[39] If the concentration of exposure is excessively high, the gas may display oxygen resulting in fatal asphyxiation.[40]
Generally, patients and workers should be educated by medical personnel on how to identify the signs and symptons of Nitrogen dioxide poisoning. Farmers and other farm workers should be educated on the proper way of food grain storage to prevent silo filler's disease.[41]
Biochemical effects
Chronic exposure to high level of Nitrogen (II) oxide results in the allosteric inhibition of Glutathione peroxidase and Glutathione S-transferase, both of which are important enzymes found in the mucous membrane antioxidant defense system, that catalyse nucleophilic attack by reduced glutathione (GSH) on non-polar compounds that contain an electrophillic Carbon and Nitrogen. This inhibition mechanisms generates free radicals that causes Peroxidation from the lipids in the mucuous membrane leading to increased peroxidized eyrthrocyte lipids, a reaction that proceeds by a free radical chain reaction mechanism that result in oxidative stress.[42] These oxidative stress on the mucous membrane causes the dissociation of the GSTp-JNK complex, oligomerization of GSTP and induction of the JNK pathway, resulting in apoptosis or inflammation of the bronchioles and Pulmonary alveolus in mild cases.[43] On migrating to the bloodstream, Nitrogen dioxide poisoning result in an irreversible inhibition of the erythrocite membrane acetylcholinesterase which may lead to muscular paralysis, convulsions, Bronchoconstriction, the narrowing of the airways in the lungs (bronchi and bronchioles) and death by asphyxiation.[44][45][46] It also causes a decrease in Glucose-6-phosphate dehydrogenase which may results in Glucose-6-phosphate dehydrogenase deficiency known as favism, a condition that predisposes to hemolysis (spontaneous destruction of red blood cells).[47] Acute and chronic exposure also reduces Glutathione reductase, an enzyme that catalyzes the reduction of glutathione disulfide (GSSG) to the sulfhydryl form glutathione (GSH), which is a critical molecule in resisting oxidative stress and maintaining the reducing environment of the cell.[48][49][50]
Reproductive effects
Exposure to Nitrogen (II) oxide have a significant effects on male reproductive system by inhibiting the production of Sertoli cell, a "nurse" cell of the testicles that is part of a seminiferous tubule and helps in the process of spermatogenesis.[51] These effects consequently retard the production of sperm cell. The effects of "Nitrogen (II) oxide poisoning of female reproduction may be linked with the effects of oxidative stress in female reproduction.[52] Nitrogen (II) oxide poisoning disrupt the balance of Reactive oxygen species, ROS which results in OS and this have a significant effects on female reproductive life span. ROS play a significant role in body physiology, from Oocite production, development and maturation to fertilization, development of embryo and pregnancy. Exposure to Nitrogen (II) oxide causes an ovulation-induced oxidative damage to the DNA of ovarian epithelium.[53] There is a growing literature on the pathological effects of ROS on female reproduction in relation to free radical-induced birth defect, abortion, hydatidiform mole and pathophysiogy of pre-eclampsia. ROS also play a significant role in etiopathogenesis of endometriosis, a disease in which tissue that normally grows inside the uterus grows outside the uterus.[54] Oxidative stress causes defective placentation which is likely to lead to placental hypoxia, shortage of oxygen in the placental as well as reperfusion injury resulting from ischemia which may lead to endothelial cell dysfunction.[55] Over-expression of oxidative stress caused by Nitrogen (II) oxide poisoning may results in ovarian epithelium inflammation and sometime leads to cancer in severe cases.[56]
References
- ^ "Update of WHO air quality guidelines". International Agency for Research on Cancer. June 2008. Retrieved 2015-08-01.
- ^ "Nitrogen dioxide". US EPA. Retrieved August 1, 2015.
- ^ "Indoor Air". United States Environmental Protection Agency. Retrieved August 1, 2015.
- ^ Ashok, Pandey (2014). Pretreatment of Biomass: Processes and Technologies. USA: Elsevier. p. 202. ISBN 0128003960. Retrieved August 1, 2015.
- ^ "Nitrogen dioxide - WHO Guidelines for Indoor Air Quality: Selected". PubMed. Retrieved August 1, 2015.
- ^ Belanger K, Gent JF, Triche EW, Bracken MB, Leaderer BP (February 1, 2006). "Association of indoor nitrogen dioxide exposure with respiratory symptoms in children with asthma". 173 (3): 297–303. doi:10.1164/rccm.200408-1123OC. PMC 2662932. PMID 2662932.
{{cite journal}}
: Cite journal requires|journal=
(help)CS1 maint: multiple names: authors list (link) - ^ "Nitrogen oxides limits: Chicago would fail to meet Obama's tougher". Chicargo Tribune. Retrieved August 1, 2015.
- ^ "Nitrogen Dioxide". American Lung Association. Retrieved August 1, 2015.
- ^ "Hazardous Substances Data Bank (HSDB) [online database]. Nitrogen dioxide". National Library of Medicine. Retrieved August 1, 2015.
- ^ "Indoor pollution from heating". PubMed. 1996. Retrieved August 1, 2015.
- ^ ". Determinants of nitrogen dioxide concentrations in indoor ice skating rinks. American Journal of Public Health". 88 (12). 1998: 1781–6.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Glorennec P; et al. (2008). "Is a quantitative risk assessment of air quality in underground parking garages possible?". 18 (4): 283–92.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Leung R; et al. (1998). "Indoor environment of residential homes in Hong Kong – relevance to asthma and allergic disease". 28 (5): 585–90.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Hagenbjork-Gustafsson A; et al. (1996). "Measurements of indoor and outdoor nitrogen dioxide concentrations using a diffusive sampler". 12 (9): 1261–1264.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Levy JI; et al. (1998). "Impact of residential nitrogen dioxide exposure on personal exposure: an international study". 48 (6): 553–60.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Lambert WE; et al. (1993). "Nitrogen dioxide and respiratory illness in children. Part II. Assessment of exposure to nitrogen dioxide". 58 (33–50): 51–80.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Simoni M; et al. (2002). "The Po River Delta (north Italy) indoor epidemiological study: effects of pollutant exposure on acute respiratory symptoms and respiratory function in adults". 57 (2): 130–6.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Garcia-Algar O; et al. (2003). "Sources and concentrations of indoor nitrogen dioxide in Barcelona, Spain". 53 (11): 1312–7.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Kodama Y; et al. (2002). "Environmental NO2 concentration and exposure in daily life along main roads in Tokyo". 89 (3): 236–44.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Nakai S, Nitta H, Maeda K. (1995). "Respiratory health associated with exposure to automobile exhaust. II. Personal NO2 exposure levels according to distance from the roadside". 5 (2): 125–36.
{{cite journal}}
: Cite journal requires|journal=
(help)CS1 maint: multiple names: authors list (link) - ^ Blondeau P; et al. (2005). "Relationship between outdoor and indoor air quality in eight French schools". 15 (1): 2–12.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Weschler CJ; et al. (2006). "Workgroup report: indoor chemistry and health. Environmental Health Perspectives". 11 (3): 442–6.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Kattan M; et al. (2007). "Health effects of indoor nitrogen dioxide and passive smoking on urban asthmatic children". 120 (3): 618–24.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Baxter LK; et al. (2007). "Predictors of concentrations of nitrogen dioxide, fine particulate matter, and particle constituents inside of lower socioeconomic status urban homes". 17 (5): 433–44.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Baxter LK; et al. (2007). "Predicting residential indoor concentrations of nitrogen dioxide, fine particulate matter, and elemental carbon using questionnaire and geographic information system based data". 41 (31): 6561–6571.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Hansel N; et al. (2008). "A longitudinal study of indoor nitrogen dioxide levels and respiratory symptoms in inner city children with asthma". 116 (10): 1428–32.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Pilotto LS; et al. (1997). "Respiratory effects associated with indoor nitrogen dioxide exposure in children". 26 (4): 788–96.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Lévesque B; et al. (2001). "Wood-burning appliances and indoor air quality". 281 (1–3): 46–62.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Kumie A; et al. (2008). "lMagnitude of indoor NO2 from biomass fuels in rural settings of Ethiopia". 19 (1): 14–21.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Lawrence AJ; et al. (2005). "Indoor/outdoor relationships of carbon monoxide and oxides of nitrogen in domestic homes with roadside, urban and rural locations in a central Indian region". 15 (2): 76–82.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ "UK set for war on NO2 emissions". Times of India. Retrieved August 2, 2015.
- ^ "London set to declare war on diesel". The Irish Times. Retrieved August 2, 2015.
- ^ "Air pollution in London's Oxford Street has already breached the". Independent News. Retrieved August 2, 2015.
- ^ "UK set for war on NO2 emissions". India Environment Portal. Retrieved August 2, 2015.
- ^ "UK faces European court over coal plant emissions". The Guardian News. Retrieved August 2, 2015.
- ^ Garrett MH, Hooper MA, Hooper BM (1996). "Nitrogen dioxide in Australian homes: levels and sources". 49 (1): 76–81.
{{cite journal}}
: Cite journal requires|journal=
(help)CS1 maint: multiple names: authors list (link) - ^ Zota A; et al. (2005). "Ventilation in public housing: implications for indoor nitrogen dioxide concentrations". 15 (6): 393–401.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Dennekamp M; et al. (2001). "Ultrafine particles and nitrogen oxides generated by gas and electric cooking". 58 (8): 511–6.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Lee K; et al. (2002). "Nitrous acid, nitrogen dioxide, and ozone concentrations in residential environments". 110 (2): 145–50.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ "Nitrogen dioxide toxicity". medscape.com. Retrieved August 1, 2015.
- ^ Spannhake EW; et al. (2002). "Synergism between rhinovirus infection and oxidant pollutant exposure enhances airway epithelial cell cytokine production". 110 (7): 665-170.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Sanga M, ichinose T (1991). "Biochemical effects of combined gases of nitrogen dioxide". 66 (2): 121–32.
{{cite journal}}
: Cite journal requires|journal=
(help) - ^ Persinger RL; et al. (2002). "Molecular mechanisms of nitrogen dioxide induced epithelial injury". 234–235 (1–2): 71–80.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ "National Pesticide Information Center-Diazinon Technical Fact Sheet" (PDF). Retrieved 24 February 2012.
- ^ Drachman, D.B.; Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. Kasper, D.L., eds (1998). Harrison's Principles of Internal Medicine (14 ed.). The McCraw-Hill Companies. pp. 2469–2472. ISBN 978-0-07-020291-7.
{{cite book}}
:|author2=
has generic name (help)CS1 maint: multiple names: authors list (link) - ^ Raffe, RB. Autonomic and Somatic Nervous Systems in Netter's Illustrated Pharmacology. Elsevier Health Science. p. 43. ISBN 978-1-929007-60-8.
- ^ Sagai M.; et al. (1984). "Studies on the biochemical effects of nitrogen dioxide. IV. Relation. Relation between the changes of lipid peroxidation and the antioxidative protective system in Rat lungs upon life span exposure to low levels of Nitrogen dioxide". 73 (3): 444–56.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Meister A (November 1988). "Glutathione metabolism and its selective modification". J. Biol. Chem. 263 (33): 17205–8. PMID 3053703.
- ^ Mannervik B (August 1987). "The enzymes of glutathione metabolism: an overview". Biochem. Soc. Trans. 15 (4): 717–8. PMID 3315772.
- ^ "Biochemical and metabolic response to nitrogen dioxide-induced enthothelia injury". 9 (3). 1987: 3–20.
{{cite journal}}
: Cite journal requires|journal=
(help) - ^ Ashok Agawa; et al. (2005). "Role of oxidative stress in female reproduction". 3 (28): 3–28.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Ashok Agarwal; et al. (2005). "Role of oxidative stress in female reproduction". 3 (28): 1477-7827.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Ashok Agawa; et al. (2012). "The effects of oxidative stress on female reproduction: a review". 10 (49): 1477-7827.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Gupta S; et al. (2007). "The role of oxidative stress in spontaneous abortion and recurrent". 62 (5): 335–47.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ Monis Bilial Shamsi; et al. (2011). "Sperm DNA damage & oxidative stress in recurrent spontaneous". 133 (5): 550–551.
{{cite journal}}
: Cite journal requires|journal=
(help); Explicit use of et al. in:|author=
(help) - ^ "Role of oxidative stress in female reproduction". Cleaveland Clinic. Retrieved August 3, 2015.