Protective effects of N-acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners.
OBJECTIVE
Long-term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N-acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks.


METHODS
Seventy-two male Wistar albino rats were used and divided into two groups: one group inhaled only thinners (TI), while the other inhaled TI plus NAC. Rats in the TI and TI + NAC groups were divided into four subgroups (each consisting of eight rats) according to the duration of exposure to TI: 2, 4, 6 and 8 weeks. A control group (n = 7) of rats inhaled neither TI nor NAC. Malondialdehyde (MDA) and GSH levels, and superoxide dismutase (SOD) activities were determined in the lung tissues. Histopathological findings were evaluated as acute and chronic changes in the alveoli and interstitium in the TI and TI + NAC groups and compared with those in the control group.


RESULTS
While tissue MDA levels in the groups inhaling TI for 4, 6 and 8 weeks were significantly higher than those in the control groups (P < 0.01, P < 0.01, P < 0.0001, respectively), GSH levels were significantly lower (P < 0.05, P < 0.01, P < 0.01, respectively). Tissue SOD activities in the groups inhaling TI for 6 and 8 weeks were significantly lower than those in the control group (P < 0.05, P < 0.01, respectively). In the TI group, MDA levels were significantly increased (P < 0.01) with increasing duration of inhalation (from the second week through to the eighth week), while GSH levels and SOD activities were significantly decreased (P < 0.01, P < 0.01). Tissue MDA levels were significantly lower in the TI + NAC groups across all inhalation periods, when compared with the TI groups (P < 0.01, P < 0.0001, P < 0.0001, P < 0.0001, respectively). Tissue GSH levels in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.01, P < 0.01, P < 0.0001). Tissue SOD activities in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.0001, P < 0.05, P < 0.0001). Pathological examinations with light microscopy did not show any beneficial effect of NAC application in terms of deferring or alleviating the negative effects of TI.


CONCLUSIONS
Thinners are agents that cause imbalance between oxidants and antioxidants produced by aerobic cellular systems. This imbalance between oxidant and antioxidant systems is decreased by the effect of NAC. However, ultrastructural studies may be needed to substantiate this evidence morphologically, as light microscopy was inconclusive.
Dillioglugil
Meltem Ozlen
MO
Department of Clinical Biochemistry, Faculty of Medicine, Kocaeli University, Turkey. mozden@superonline.com
Ilgazli
Ahmet
A
Maral
Hale
H
Sengul
Canan
C
Ozdemir
Gulsen
G
Ercin
Cengiz
C
D000111:Acetylcysteine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008853:Microscopy; D009930:Organic Chemicals / Q000009:adverse effects* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000009:adverse effects* / Q000737:chemistry; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D009930:Organic Chemicals; D012997:Solvents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine