Hayvan modelinde elektronik sigara buharı ve sigara dumanının pulmoner toksik etkilerinin değerlendirilmesi
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Tarih
2020
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Özellikle genç yaş grubu dahil olmak üzere, elektronik sigara kullanımının ve tütün
sigaraya göre daha az pulmoner toksik olduğu yanlış bilgisinin kamuoyunda
yaygınlaşması, elektronik sigara(E-sigara) kullanımının toplumda normal bir davranış
olarak kabul görmesi, hali hazırda bilinmektedir. Ancak bilinenin aksine anket çalışmaları,
hayvan deneyleri, bildirilen olgu sunumları ve olgu serileri, nadir insan çalışmaları, Esigaraların tütün sigaralar kadar zararlı olduğunu göstermektedir. Ancak bu çalışmaların
hiçbirinde elektronik sigara buharının pulmoner toksik etkilerinin, elektronik sigara
likitlerinin bileşiğinde bulunan propilen glikol(PG), vegetable gliserin(VG), çeşitli
aromalar ve isteğe göre seçilen düzeyde nikotin komponentlerinden hangisine/hangilerine
bağlı olduğu açıkça ortaya konulmamıştır. Yine, tütün sigaradan farklı olarak E-sigaranın
çalışma mekanizması gereği ısınma sonucu oluşan sigara buharının toksik etkilerinin tütün
sigaralarda yanma sonucu oluşan sigara dumanının toksik etkileriyle benzer veya farklı
olup olmadığı kesin olarak bilinmemektedir.
Deneysel olarak planlanmış bu çalışmada, öncelikli olarak E-sigara buharının
sıçanların akciğer bronş ve alveol epiteli üzerindeki potansiyel histopatolojik etkilerinin ve
ayrıca akciğer parankim dokusu ve serumda inflamatuvar ve oksidatif stres etkilerinin,
tütün sigara dumanıyla karşılaştırılmalı olarak değerlendirilmesi; ikinci olarak da bu olası
toksik etkiler üzerinde E-sigara komponentlerinin (PG, VG, aroma vericiler ve nikotin)
rollerinin araştırılması amaçlanmıştır.
Yöntem: Çalışmaya alınan, Wistar albino ırkına ait, 5 aydan büyük, 60 adet dişi sıçan, altı
eşit gruba ayrılarak incelenmiştir. İlk 4 gruptaki sıçanlar 6 hafta boyunca, haftanın 5 günü,
günde iki kez ve 2 saat/gün E-sigaranın değişik komponentlerinin buharına maruz
bırakıldılar. Birinci grup; yalnızca VG/PG içeren E-sigara buharına, ikinci grup; VG/PG ve
nikotin içeren E-sigara buharına, üçüncü grup; VG/PG ve aroma içeren E-sigara buharına,
dördüncü grup ise; VG/PG, aroma ve nikotin içeren E-sigara buharına maruz kaldı. Beşinci
grup, tütün sigara dumanına maruz kalan grup olup bu gruptaki sıçanlar da 6 hafta süreyle
vi
haftanın 5 günü, günde iki kez ve 2 saat/gün tütün sigara dumanına maruz bırakıldı.
Kontrol grubundaki sıçanlar ise çalışma sürecinde diğerleri ile benzer şartlarda tutulup
herhangi bir kimyasal veya fiziksel uyarana maruz bırakılmadılar. Tütün sigara olarak
nikotin değeri 1 mg/adet olandan seçildi. E-sigarada nikotin oranı, 12 mg/ml olarak
kullanıldı. Çalışmada, sıçanlar tüm vücut buhar/dumanına maruz kaldılar.
6 haftanın sonunda, sıçanlar anestezi altında, önce biyokimya için kardiyak kan alma
işlemi yapılması ardından sakrifiye edilerek uygun doku örnekleri alındı.
Histopatolojik değerlendirme, çift kör uzman bir patolog tarafından yapıldı. Amfizem
oranı, santral hava yollarında inflamasyon ve mevcut inflamatuvar hücreler, interstisyel
alanda inflamasyon ve sorumlu inflamatuvar hücreler, metaplazi, hiperplazi gibi atipik
değişiklikler, peribronşial lenfoid hiperplazi ve alveoler makrofaj yoğunluğu açısından
değerlendirildi. Ayrıca oilred boyama ile alveoler lipid yüklü makrofaj yoğunluğu, lipid
yük indexi ve bir alveoldeki ortalama lipid yüklü makrofaj sayısı açısından değerlendirildi
ve sonuçlar skorlanarak kaydedildi.
Biyokimyasal değerlendirmede, kanlarının santrifüjüyle elde edilen plazma
örneklerinde, rat IL-6 ve rat IL-10, Total Antioksidan Seviyesi(TAS) ve Total Oksidan
Seviyesi(TOS) ve sıçanların diğer akciğer doku örneklerinde doku spesifik IL-6, IL-10,
Total Antioksidan Seviyesi(TAS) ve Total Oksidan Seviyesi(TOS) analizleri yapılarak
sonuçlar kaydedildi.
Çalışma sonunda elde edilen veriler istatistiksel değerlendirme ile analiz edildi.
Bulgular:Çalışmamızda, sigara grubunda, kontrol grubuna göre, plazma IL-6(p=0,021) ve
doku IL-6(p<0,001), TOS(p<0,001), OSİ(p<0,001) değerleri istatistiki olarak anlamlı
şekilde artarken, doku TAS(p<0,001) düzeyi anlamlı olarak daha düşüktü. Kontrole göre,
PG/VG+aroma+nikotin içeren E-likit bulunan E-sigara grubunda, doku düzeyinde IL-10
düzeyi (p=0,016) anlamlı olarak daha yüksek olarak tespit edilmişken, doku TAS(p=0,029)
ve doku TOS(p<0,001) düzeyleri anlamlı olarak daha düşük olarak ölçüldü. Bu iki değerin
oranı olan oksidatif stres indeksindeki artış ise anlamlıydı(p=0,001).
Likit içeriğinde PG/VG+aroma+nikotin bulunan E-sigara grubu ile sigara grubunun
karşılaştırmalı sonuçlarına göre, sigara grubunda, plazma IL-6(p=0,05) ve doku IL6(p<0,001) seviyeleri iledoku TOS(total oksidan durum)(p<0,001) ve doku OSİ (oksidatif
stres indeksi)(p<0,001)düzeyleri anlamlı olarak daha yüksek olarak ölçülürken, doku IL-
vii
10 seviyesi ise daha düşük olarak tespit edilmiştir(p<0,001). Bu sonuçlarla sigara grubu, en
çok inflamatuvar yanıt oluşturan ve oksidatif stresi en çok artıran grup olarak
değerlendirildi.
Çalışmamızda, PG/VG buharı inhale eden grupta, kontrole göre, doku IL-10(p=0,007)
düzeyinde anlamlı artış, doku TOS(p<0,001) düzeyinde anlamlı şekilde düşüş tespit ettik.
Patolojik değerlendirmede ise, PG/VG grubunda, santral hava yollarında
inflamasyon(p=0,029) ve alveoler makrofaj yoğunluğunda(p=0,002) kontrole göre, anlamlı
artışlar olduğunu ortaya çıkardık.
Likit içeriğindeki PG/VG’ye aroma eklendiğinde, kontrole göre, doku IL-10 (p=0,029)
seviyesinde anlamlı artış ile antiinflamatuvar bir etki gözlerken, histopatolojik olarak
kontrole göre, amfizem oranı(p=0,005), santral hava yollarında inflamasyon(p=0,007),
interstisyel alanda inflamasyon (p=0,022) ve alveoler makrofaj yoğunluğunda(p=0,007)
anlamlı artış ile pulmoner toksik bir etki tespit ettik.
Bizim çalışmamızda, likit içeriğindeki PG/VG’ye nikotin eklendiğinde, kontrole göre,
bu grupta, doku TOS(p=0,047)ve doku OSI(p<0,001) anlamlı olarak daha yüksek tespit
edilirken, doku TAS(p<0,0019) değeri anlamlı olarak daha düşük olarak saptandı. Kontrol
grubuna göre, 1 alveoldeki lipit yüklü makrofaj sayısında(p=0,002), lipit yüklü makrofaj
yüzdesi(p=0,003), lipit yük indeksinde(p=0,012), amfizem oranında(p=0,003), santral hava
yollarındaki inflamasyon yüzdesinde(p=0,013) ve alveoler makrofaj yoğunluğunda
da(p=0,001) bu grupta anlamlı artışlar tespit edildi.
Kontrole göre, PG/VG+aroma+nikotin içeren E-likit bulunan E-sigara grubunda doku
düzeyinde IL-10 düzeyi (p=0,016) anlamlı olarak daha yüksek olarak tespit edilmişken,
doku TOS(p<0,001) düzeyleri anlamlı olarak daha düşük olarak ölçüldü. Ancak
histopatolojik düzeyde, kontrole kıyasla, lipit yüklü makrofaj yüzdesi(p<0,001), lipit yük
indeksi(p<0,001), bir alveoldeki ortalama lipit yüklü makrofaj sayısı(p<0,001), amfizem
oranı(p=0,003), santral hava yollarında(p=0,003) ve interstisyel alanda inflamasyon
yüzdesi(p=0,012) ve alveolar makrofaj yoğunluğu(p=0,008) istatistiki anlamlı olarak
artmış olarak tespit edildi.
PG/VG+nikotin içeren E-likit buharına maruz bırakılan 2.grupta,
4.gruba(PG/VG+aroma+nikotin) göre, doku IL-10(p<0,001) düzeyi anlamlı olarak daha
viii
düşük olarak saptanırken, doku TOS değeri(p<0,001) anlamlı olarak daha yüksek olarak
değerlendirildi.
PG/VG+aroma+nikotin grubunda, kontrole kıyasla, lipit yüklü makrofaj yüzdesi(p<0,001),
lipit yük indeksi(p=0,001), bir alveoldeki ortalama lipit yüklü makrofaj sayısı(p<0,001),
amfizem oranı(p=0,003), santral hava yollarında(p=0,003) ve interstisyel alanda
inflamasyon yüzdesi(p=0,012) ve alveolar makrofaj yoğunluğu(p=0,008) istatistiki anlamlı
olarak artmış olarak tespit edildi.
Sigara grubunda ise, kontrole kıyasla, amfizem oranı(p=0,003) ve santral hava
yollarındaki inflamasyon yüzdesi(p=0,004) değerlendirildiğinde, sigara grubunda
istatistiksel olarak anlamlı artış görüldü. PG/VG+aroma+nikotin grubu, sigara grubuyla
kıyaslandığında, lipit yüklü makrofaj yüzde(p=0,008), sayısında(p=0,004) ve lipit yük
indeksinde(p=0,003) grup 4’te anlamlı olarak artış tespit edildi.
PG/VG grubunda, kontrole göre, santral hava yollarında inflamasyon(p=0,029) ve alveoler
makrofaj yoğunluğunda(p=0,002) anlamlı artışlar tespit edildi. 1.grupta, PG/VG+nikotin
içeren gruba göre, lipit yüklü makrofaj yüzdesi(p<0,001), 1 alveoldeki ortalama lipit yüklü
makrofaj sayısı(p<0,001), lipit yük indeksi(p<0,001) anlamlı olarak daha düşük olarak
saptandı. PG/VG grubunda, PG/VG+aroma içeren gruba göre, lipit yük indeksi(p=0,046)
anlamlı olarak daha düşükken, alveoler makrofaj younluğu(p değeri=0,009) değerleri
anlamlı olarak daha yüksek olarak tespit edildi. PG/VG grubunda, PG/VG+aroma+nikotin
içeren gruba göre, lipit yüklü makrofaj sayısı(p<0,001), lipit yüklü makrofaj
yüzdesi(p<0,001), lipit yük indeksi(p<0,001) seviyeleri ve amfizem oranı(p=0,032)
anlamlı olarak daha düşük tespit edildi.
PG/VG+nikotin inhale eden grupta, kontrol grubuna göre, 1 alveoldeki lipit yüklü
makrofaj sayısında(p=0,002), lipit yüklü makrofaj yüzdesi(p=0,003), lipit yük
indeksinde(p=0,012), amfizem oranında(p=0,003), santral hava yollarındaki inflamasyon
yüzdesinde(p=0,013) ve alveoler makrofaj yoğunluğunda(p=0,001) anlamlı olarak
yükseklik tespit edildi. PG/VG+nikotin içeren grupta, PG/VG+aroma içeren gruba göre, 1
alveoldeki lipit yüklü makrofaj sayısı(p=0,002), lipit yük indeksi(p=0,015), lipit yüklü
makrofaj yüzdesi(p=0,004) ve alveoler makrofaj yoğunluğu(p=0,014) anlamlı olarak daha
yüksek olarak tespit edildi.
ix
PG/VG+aroma içeren grupta, kontrole göre, amfizem oranı(p=0,005), santral hava
yollarında inflamasyon yüzdesi(p=0,007), interstisyel alanda inflamasyon
yüzdesi(p=0,022) ve alveoler makrofaj yoğunluğu yüzdesinde(p=0,007) anlamlı olarak
artış tespit edildi. PG/VG+aroma içeren grupta, PG/VG+aroma+nikotin içeren gruba göre
göre,1 alveoldeki lipit yüklü makrofaj sayısı(p<0,001), lipit yüklü makrofaj
yüzdesi(p<0,001), lipit yük indeksi(p<0,001) anlamlı olarak daha düşük olarak tespit
edildi.
PG/VG+aroma+nikotin grupta, kontrole göre, 1 alveoldeki ortalama lipit yüklü
makrofaj sayısı(p<0,001), lipit yüklü makrofaj yüzdesi(p<0,001), lipit yük
indeksi(p<0,001), amfizem oranı(p=0,003), santral hava yollarında inflamasyon
yüzdesi(p=0,004) anlamlı olarak yüksek bulundu.
E-likit bileşenlerini değerlendirdiğimiz bu çalışmamızın analizi sonucunda, prooksidan
ve proinflamatuvar etkinin sebebinin likit içeriğindeki nikotinin olduğunu, aromanın
nikotin etkisini potansiyelize etmediğini, aksine, bir mekanizma ile antiinflamatuvar ve
antioksidan tarafa doğru nikotin etkisini azaltabileceğini düşünmekteyiz. Ancak
histopatolojik düzeyde, aromanın da, amfizem, santral hava yollarında inflamasyon,
interstisyel alanda inflamasyon ve alveoler makrofaj yoğunluğunda anlamlı artışlara neden
olduğunu tespit ettik.
Sonuç:Biyokimyasal sonuçlarımıza göre; asıl prooksidan ve proinflamatuvar etkinin
sebebinin likit içeriğindeki nikotinin olduğu, aromanın nikotin etkisini potansiyelize
etmediği, tersine bir mekanizma ile antiinflamatuvar ve antioksidan tarafa doğru nikotin
etkisini azaltabileceği tespit edildi.Patolojik değerlendirmelerimiz ışığında ise;oil red
boyama ile değerlendirilen makrofaj yüzdesi, lipit yük indeksi, bir alveoldeki ortalama lipit
yüklü makrofaj sayısındaki ve hematoksilen&eosin boyama ile değerlendirilen, amfizem
oranı, santral hava yollarında ve interstisyel alanda inflamasyon yüzdesi, peribronşial
lenfoid hiperplazi ve alveolar makrofaj yoğunluğu gibi parametrelerde anlamlı
değişikliklere nikotinin yol açtığı düşünülmüştür.
Objective: It is already known that electronic cigarette use and tobacco cigarette are less pulmonary toxic, especially in the younger age group, that the use of electronic cigarettes (E-cigarettes) is accepted as a normal behavior in the public. However, contrary to what is known, survey studies, animal experiments, reported case reports and case series, rare human studies show that E-cigarettes are as harmful as tobacco cigarettes. However, none of these studies clearly revealed which pulmonary toxic effects of electronic cigarette vapor, propylene glycol (PG), vegetable glycerin (VG), various flavors and optionally selected levels of nicotine components in the composition of electronic cigarette liquids. Again, unlike tobacco cigarettes, it is not known exactly whether the toxic effects of cigarette vapors resulting from warming are similar or different from the toxic effects of cigarette smoke caused by combustion in tobacco cigarettes. In this experimentally planned study, the evaluation of the potential histopathological effects of E-cigarette vapor on the lung bronchus and alveolar epithelium of rats as well as the effects of inflammatory and oxidative stress in lung parenchymal tissue and serum compared to tobacco cigarette smoke; Secondly, it is aimed to investigate the roles of Ecigarette components (PC, VG, flavors and nicotine) on these possible toxic effects. Method: 60 female rats of Wistar albino race, more than 5 months old, included in the study were divided into six equal groups. The rats in the first 4 groups were exposed to the vapors of different components of the E-cigarette for 6 weeks, 5 days a week, twice a day and 2 hours / day. The first group; to the E-cigarette vapor containing only VG / PG, the second group; E-cigarette vapor containing VG / PG and nicotine, third group; E-cigarette vapor containing VG / PG and aroma is the fourth group; VG / PG was exposed to Ecigarette vapor containing aroma and nicotine. The fifth group was exposed to tobacco cigarette smoke, and the rats in this group were exposed to tobacco cigarette smoke 5 days a week, twice daily and 2 hours / day for 6 weeks. Rats in the control group, on the other hand, were not exposed to any chemical or physical stimuli during the study period under similar conditions. Tobacco cigarettes were selected from nicotine value of 1 mg / piece. xii The nicotine ratio in E-cigarette was used as 12 mg / ml. In the study, rats were exposed to whole body vapors / fumes. At the end of 6 weeks, rats under anesthesia, cardiac blood collection for biochemistry, then sacrified and appropriate tissue samples were taken. Histopathological evaluation was performed by a double-blind specialist pathologist. The rate of emphysema, inflammation in the central airways and existing inflammatory cells, inflammation in the interstitial area and responsible inflammatory cells, metaplasia, hyperplasia such as atypical changes, peribronchial lymphoid hyperplasia and alveolar macrophage density were evaluated. In addition, oil red staining was evaluated in terms of alveolar lipid-laden macrophage density, lipid load index and the average number of lipidladen macrophages in an alveolar, and the results were recorded. Results: In our study, compared to the control group, plasma IL-6 (p=0.021) and tissue IL6 (p<0.001), TOS (p<0.001), OSI (p<0.001) values were statistically significant in the smoking group. while increasing tissue TAS (p<0.001) level was significantly lower. In the E-cigarette group with PG / VG + flavor + nicotine containing E-liquid compared to the control, IL-10 level (p=0.016) at tissue level was found to be significantly higher, while tissue TAS (p=0.029) and tissue TOS (p<0.001) levels were measured significantly lower. The increase in the oxidative stress index, the ratio of these two values, was significant (p=0.001). According to the comparative results of the E-cigarette group with PG / VG + aroma + nicotine in liquid content and the cigarette group, in the cigarette group, tissue levels of plasma IL-6 (p=0.05) and tissue IL-6 (p<0.001) TOS (total oxidant status) (p<0.001) and tissue OSI (oxidative stress index) (p<0.001) levels were measured significantly higher, while tissue IL-10 level was found to be lower (p< 0.001). With these results, the smoking group was evaluated as the group that produced the most inflammatory response and increased the oxidative stress the most. In our study, we found a significant increase in the tissue IL-10 (p=0.007) level and a significant decrease in the tissue TOS (p<0.001) level in the PG / VG vapor group, compared to the control. In the pathological evaluation, we found significant increases in inflammation in the central airways (p=0.029) and alveolar macrophage density (p=0.002) in the PG / VG group compared to the control. xiii When flavor is added to PG / VG in the liquid content, tissue has an anti-inflammatory effect with a significant increase in IL-10 (p=0.029) compared to the control, while histopathologically, emphysema rate (p=0.005), inflammation in central airways (p=0.007), inflammation in the interstitial area (p=0.022) and a significant increase in alveolar macrophage density (p=0.007), and a pulmonary toxic effect. İn our study, when nicotine was added to PG / VG in liquid content, tissue TOS (p=0.047) and tissue OSI (p<0.001) were found to be significantly higher in this group compared to the control, while tissue TAS (p<0.0019) value was found to be significantly lower. According to the control group, the number of lipid loaded macrophages in 1 alveoli (p=0.002), the percentage of lipid loaded macrophages (p=0.003), the lipid load index (p=0.012), the emphysema rate (p=0.003), Significant increases were found in the percentage of inflammation (p=0.013) and alveolar macrophage density (p=0.001) in this group. The tissue level of IL-10 (p=0.016) was found to be significantly higher in the Ecigarette group containing PG / VG, aroma, nicotine containing E-liquid compared to the control, while tissue TOS (p<0.001) levels were found to be significantly higher. measured as lower. However, at the histopathological level, compared to control, the percentage of lipid-loaded macrophages (p<0.001), lipid load index (p=0.001), the average number of lipid-loaded macrophages in an alveoli (p<0.001), emphysema rate (p=0.003), percentage of inflammation in central airways (p=0.003) and interstitial area (p=0.012) and alveolar macrophage density (p=0.008) were found to be statistically significantly increased. In the 2nd group exposed to PG / VG + nicotine containing e-liquid vapor, tissue IL10 (p<0.001) level was found to be significantly lower than the 4th group (PG / VG + aroma + nicotine), while tissue TOS value (p<0.001) was considered to be significantly higher. Percentage of lipid-loaded macrophages (p<0.001), lipid load index (p=0.001), average number of lipid-loaded macrophages in an alveoli (p<0.001), emphysema in PG / VG + aroma + nicotine group compared to control ratio (p=0.003), percentage of inflammation in the central airways (p=0.003) and the interstitial area (p=0.012) and alveolar macrophage density (p=0.008) were found to be statistically significantly increased. xiv In the smoking group, when the emphysema rate (p=0.003) and the percentage of inflammation in the central airways (p=0.004) were evaluated, a statistically significant increase was observed in the smoking group. When the PG / VG + aroma + nicotine group was compared to the cigarette group, a significant increase in lipid-loaded macrophage percentage (p=0.008), number (p=0.004) and lipid load index (p=0.003) was found in group 4. Significant increases in inflammation in the central airways (p=0.029) and alveolar macrophage density (p=0.002) were detected in the PG / VG group compared to control. In group 1, compared to the PG / VG + nicotine containing group, the percentage of lipidloaded macrophages (p<0.001, the average number of lipid loaded macrophages in 1 alveoli (p<0.001), lipid load index (p<0.001) was significant In the PG / VG group, lipid load index (p=0.046) was significantly lower than the PG / VG + aroma group, while alveolar macrophage density (p=0.009) values were found to be significantly higher. In the PG / VG group, the number of lipid loaded macrophages (p value: <0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index (p<0.001) compared to the PG / VG + aroma + nicotine group.) and emphysema rate (p=0.032) were significantly lower. In the PG / VG + nicotine inhaler group, compared to the control group, the number of lipid-loaded macrophages in 1 alveoli (p=0.002), the percentage of lipid-loaded macrophages (p=0.003), the lipid load index (p=0.012), the emphysema rate ( p=0.003), percentage of inflammation in central airways (p=0.013) and alveolar macrophage density (p=0.001) were found to be significantly higher. In the group containing PG / VG + nicotine, the number of lipid-loaded macrophages in 1 alveoli (p=0.002), lipid load index (p=0.015), percentage of lipid-loaded macrophages (p=0.004) compared to the group containing PG / VG + aroma. and alveolar macrophage density (p=0.014) were found to be significantly higher. In the group containing PG / VG + aroma, compared to control, the rate of emphysema (p=0.005), the percentage of inflammation in the central airways (p=0.007), the percentage of inflammation in the interstitial area (p=0.022), and the percentage of alveolar macrophage density (p=0.007) significant increase was detected. In the group containing PG / VG + aroma, compared to the group containing PG / VG + aroma + nicotine, the number of lipid-loaded macrophages in 1 alveoli (p<0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index ( p<0.001) was found to be significantly lower. xv Average number of lipid loaded macrophages in 1 alveoli (p<0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index (p<0.001) in the PG / VG + aroma + nicotine group, Emphysema rate (p=0.003), percentage of inflammation in central airways (p=0.004) were found to be significantly higher. As a result of the analysis of our study in which we evaluated the e-liquid components, we think that the reason for the pro-oxidant and pro-inflammatory effect is the nicotine in the liquid content, that the aroma does not potentialize the nicotine effect, on the contrary, it can reduce the effect of nicotine towards the anti-inflammatory and antioxidant side with a mechanism. However, at the histopathological level, we found that the aroma caused significant increases in emphysema, inflammation in the central airways, inflammation in the interstitial area and alveolar macrophage density. Conclusion: According to our biochemical results; it was determined that the main propoxy and proinflammatory effect was caused by nicotine in the liquid content, the aroma did not potentially potentiate the nicotine effect, and by a reverse mechanism it could reduce the nicotine effect towards the anti-inflammatory and antioxidant side. In the light of our pathological evaluations; Changes in parameters such as macrophage percentage evaluated by oil red staining, lipid load index, average lipid-laden macrophage count in an alveol, and the rate of inflammation in the central airways and interstitial space, significant changes in the concentration of peribronchial lymphoid hyperplasia and alveolar macrophage. It was thought to have opened.
Objective: It is already known that electronic cigarette use and tobacco cigarette are less pulmonary toxic, especially in the younger age group, that the use of electronic cigarettes (E-cigarettes) is accepted as a normal behavior in the public. However, contrary to what is known, survey studies, animal experiments, reported case reports and case series, rare human studies show that E-cigarettes are as harmful as tobacco cigarettes. However, none of these studies clearly revealed which pulmonary toxic effects of electronic cigarette vapor, propylene glycol (PG), vegetable glycerin (VG), various flavors and optionally selected levels of nicotine components in the composition of electronic cigarette liquids. Again, unlike tobacco cigarettes, it is not known exactly whether the toxic effects of cigarette vapors resulting from warming are similar or different from the toxic effects of cigarette smoke caused by combustion in tobacco cigarettes. In this experimentally planned study, the evaluation of the potential histopathological effects of E-cigarette vapor on the lung bronchus and alveolar epithelium of rats as well as the effects of inflammatory and oxidative stress in lung parenchymal tissue and serum compared to tobacco cigarette smoke; Secondly, it is aimed to investigate the roles of Ecigarette components (PC, VG, flavors and nicotine) on these possible toxic effects. Method: 60 female rats of Wistar albino race, more than 5 months old, included in the study were divided into six equal groups. The rats in the first 4 groups were exposed to the vapors of different components of the E-cigarette for 6 weeks, 5 days a week, twice a day and 2 hours / day. The first group; to the E-cigarette vapor containing only VG / PG, the second group; E-cigarette vapor containing VG / PG and nicotine, third group; E-cigarette vapor containing VG / PG and aroma is the fourth group; VG / PG was exposed to Ecigarette vapor containing aroma and nicotine. The fifth group was exposed to tobacco cigarette smoke, and the rats in this group were exposed to tobacco cigarette smoke 5 days a week, twice daily and 2 hours / day for 6 weeks. Rats in the control group, on the other hand, were not exposed to any chemical or physical stimuli during the study period under similar conditions. Tobacco cigarettes were selected from nicotine value of 1 mg / piece. xii The nicotine ratio in E-cigarette was used as 12 mg / ml. In the study, rats were exposed to whole body vapors / fumes. At the end of 6 weeks, rats under anesthesia, cardiac blood collection for biochemistry, then sacrified and appropriate tissue samples were taken. Histopathological evaluation was performed by a double-blind specialist pathologist. The rate of emphysema, inflammation in the central airways and existing inflammatory cells, inflammation in the interstitial area and responsible inflammatory cells, metaplasia, hyperplasia such as atypical changes, peribronchial lymphoid hyperplasia and alveolar macrophage density were evaluated. In addition, oil red staining was evaluated in terms of alveolar lipid-laden macrophage density, lipid load index and the average number of lipidladen macrophages in an alveolar, and the results were recorded. Results: In our study, compared to the control group, plasma IL-6 (p=0.021) and tissue IL6 (p<0.001), TOS (p<0.001), OSI (p<0.001) values were statistically significant in the smoking group. while increasing tissue TAS (p<0.001) level was significantly lower. In the E-cigarette group with PG / VG + flavor + nicotine containing E-liquid compared to the control, IL-10 level (p=0.016) at tissue level was found to be significantly higher, while tissue TAS (p=0.029) and tissue TOS (p<0.001) levels were measured significantly lower. The increase in the oxidative stress index, the ratio of these two values, was significant (p=0.001). According to the comparative results of the E-cigarette group with PG / VG + aroma + nicotine in liquid content and the cigarette group, in the cigarette group, tissue levels of plasma IL-6 (p=0.05) and tissue IL-6 (p<0.001) TOS (total oxidant status) (p<0.001) and tissue OSI (oxidative stress index) (p<0.001) levels were measured significantly higher, while tissue IL-10 level was found to be lower (p< 0.001). With these results, the smoking group was evaluated as the group that produced the most inflammatory response and increased the oxidative stress the most. In our study, we found a significant increase in the tissue IL-10 (p=0.007) level and a significant decrease in the tissue TOS (p<0.001) level in the PG / VG vapor group, compared to the control. In the pathological evaluation, we found significant increases in inflammation in the central airways (p=0.029) and alveolar macrophage density (p=0.002) in the PG / VG group compared to the control. xiii When flavor is added to PG / VG in the liquid content, tissue has an anti-inflammatory effect with a significant increase in IL-10 (p=0.029) compared to the control, while histopathologically, emphysema rate (p=0.005), inflammation in central airways (p=0.007), inflammation in the interstitial area (p=0.022) and a significant increase in alveolar macrophage density (p=0.007), and a pulmonary toxic effect. İn our study, when nicotine was added to PG / VG in liquid content, tissue TOS (p=0.047) and tissue OSI (p<0.001) were found to be significantly higher in this group compared to the control, while tissue TAS (p<0.0019) value was found to be significantly lower. According to the control group, the number of lipid loaded macrophages in 1 alveoli (p=0.002), the percentage of lipid loaded macrophages (p=0.003), the lipid load index (p=0.012), the emphysema rate (p=0.003), Significant increases were found in the percentage of inflammation (p=0.013) and alveolar macrophage density (p=0.001) in this group. The tissue level of IL-10 (p=0.016) was found to be significantly higher in the Ecigarette group containing PG / VG, aroma, nicotine containing E-liquid compared to the control, while tissue TOS (p<0.001) levels were found to be significantly higher. measured as lower. However, at the histopathological level, compared to control, the percentage of lipid-loaded macrophages (p<0.001), lipid load index (p=0.001), the average number of lipid-loaded macrophages in an alveoli (p<0.001), emphysema rate (p=0.003), percentage of inflammation in central airways (p=0.003) and interstitial area (p=0.012) and alveolar macrophage density (p=0.008) were found to be statistically significantly increased. In the 2nd group exposed to PG / VG + nicotine containing e-liquid vapor, tissue IL10 (p<0.001) level was found to be significantly lower than the 4th group (PG / VG + aroma + nicotine), while tissue TOS value (p<0.001) was considered to be significantly higher. Percentage of lipid-loaded macrophages (p<0.001), lipid load index (p=0.001), average number of lipid-loaded macrophages in an alveoli (p<0.001), emphysema in PG / VG + aroma + nicotine group compared to control ratio (p=0.003), percentage of inflammation in the central airways (p=0.003) and the interstitial area (p=0.012) and alveolar macrophage density (p=0.008) were found to be statistically significantly increased. xiv In the smoking group, when the emphysema rate (p=0.003) and the percentage of inflammation in the central airways (p=0.004) were evaluated, a statistically significant increase was observed in the smoking group. When the PG / VG + aroma + nicotine group was compared to the cigarette group, a significant increase in lipid-loaded macrophage percentage (p=0.008), number (p=0.004) and lipid load index (p=0.003) was found in group 4. Significant increases in inflammation in the central airways (p=0.029) and alveolar macrophage density (p=0.002) were detected in the PG / VG group compared to control. In group 1, compared to the PG / VG + nicotine containing group, the percentage of lipidloaded macrophages (p<0.001, the average number of lipid loaded macrophages in 1 alveoli (p<0.001), lipid load index (p<0.001) was significant In the PG / VG group, lipid load index (p=0.046) was significantly lower than the PG / VG + aroma group, while alveolar macrophage density (p=0.009) values were found to be significantly higher. In the PG / VG group, the number of lipid loaded macrophages (p value: <0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index (p<0.001) compared to the PG / VG + aroma + nicotine group.) and emphysema rate (p=0.032) were significantly lower. In the PG / VG + nicotine inhaler group, compared to the control group, the number of lipid-loaded macrophages in 1 alveoli (p=0.002), the percentage of lipid-loaded macrophages (p=0.003), the lipid load index (p=0.012), the emphysema rate ( p=0.003), percentage of inflammation in central airways (p=0.013) and alveolar macrophage density (p=0.001) were found to be significantly higher. In the group containing PG / VG + nicotine, the number of lipid-loaded macrophages in 1 alveoli (p=0.002), lipid load index (p=0.015), percentage of lipid-loaded macrophages (p=0.004) compared to the group containing PG / VG + aroma. and alveolar macrophage density (p=0.014) were found to be significantly higher. In the group containing PG / VG + aroma, compared to control, the rate of emphysema (p=0.005), the percentage of inflammation in the central airways (p=0.007), the percentage of inflammation in the interstitial area (p=0.022), and the percentage of alveolar macrophage density (p=0.007) significant increase was detected. In the group containing PG / VG + aroma, compared to the group containing PG / VG + aroma + nicotine, the number of lipid-loaded macrophages in 1 alveoli (p<0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index ( p<0.001) was found to be significantly lower. xv Average number of lipid loaded macrophages in 1 alveoli (p<0.001), percentage of lipid loaded macrophages (p<0.001), lipid load index (p<0.001) in the PG / VG + aroma + nicotine group, Emphysema rate (p=0.003), percentage of inflammation in central airways (p=0.004) were found to be significantly higher. As a result of the analysis of our study in which we evaluated the e-liquid components, we think that the reason for the pro-oxidant and pro-inflammatory effect is the nicotine in the liquid content, that the aroma does not potentialize the nicotine effect, on the contrary, it can reduce the effect of nicotine towards the anti-inflammatory and antioxidant side with a mechanism. However, at the histopathological level, we found that the aroma caused significant increases in emphysema, inflammation in the central airways, inflammation in the interstitial area and alveolar macrophage density. Conclusion: According to our biochemical results; it was determined that the main propoxy and proinflammatory effect was caused by nicotine in the liquid content, the aroma did not potentially potentiate the nicotine effect, and by a reverse mechanism it could reduce the nicotine effect towards the anti-inflammatory and antioxidant side. In the light of our pathological evaluations; Changes in parameters such as macrophage percentage evaluated by oil red staining, lipid load index, average lipid-laden macrophage count in an alveol, and the rate of inflammation in the central airways and interstitial space, significant changes in the concentration of peribronchial lymphoid hyperplasia and alveolar macrophage. It was thought to have opened.
Açıklama
Anahtar Kelimeler
E-sigara, Tütün, Sigara, İnflamasyon, Oksidasyon, Lipit yüklü makrofaj, E-cigarette, Tobacco, Cigarette, Inflammation, Oxidation, Lipid-laden macrophage
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Teke, T. (2020). Hayvan modelinde elektronik sigara buharı ve sigara dumanının pulmoner toksik etkilerinin değerlendirilmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri Bölümü Göğüs Hastalıkları Anabilim Dalı, Konya.
