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. METHODOLOGY: 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.

Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria.

BACKGROUND: High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria. METHODS: Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects. RESULTS: MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P < 0.0001, P < 0.0001; GSH: P < 0.0001, P < 0.0001; GPx: P < 0.0001, P < 0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria (P < 0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria (P < 0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients (P > 0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria (P < 0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients (r = 0.549, P < 0.0001; r = -0.385, P<0.01). CONCLUSION: Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.