Study of the effects of thymoquinone and epigallocatechin gallate on cigarette smoke- induced oxidative stress and inflammatory responses in guinea pigs

الملخص EN

Background : Cigarette smoke (CS) is implicated in many pulmonary disorders including chronic obstructive pulmonary disease (COPD).This disease is a major and increasing global health problem that is now a leading cause of death.

COPD is associated with a chronic inflammatory response, predominantly in small airways and lung parenchyma.

Several mechanisms may explain how CS can cause airway inflammation and subsequent disease.

These include an imbalance between proinflammatory and anti-inflammatory cytokines, oxidative stress, and an imbalance between proteases and anti-protease enzymes.

Because of increased concern in using agents from plant origin in prophylaxis of many diseases, thymoquinone (TQ), the main active constituent of the volatile oil of Nigella sativa seeds, and (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol isolated from green tea were investigated for their possible modulatory effects on lung responses to CS.

Aim : The present work aimed to study the possible modulatory effects of TQ and EGCG on lung responses to CS.

Methods : Guinea pigs were exposed to the whole CS for 5 days per week, for 8 weeks.

The sham exposure animals were exposed to room air.

The CS exposed animals were divided into untreated group, TQ-(50 mg / kg body weight) treated group, and EGCG-(2 mg / kg body weight) treated group.

Markers of inflammation (IL-8, LTB4, neutrophil elastase (NE), and TNF-?) were assayed in bronchoalveolar lavage fluid (BALF) from those animals.

Lung tissue homogenate were assayed for myeloperoxidase (MPO) activity and markers of oxidative stress [superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA)].

Results : CS induced significant lung inflammation as evidenced by the significantly increased levels of IL-8, LTB4, NE, and TNF-? (in BALF) and MPO (in lung tissue homogenate).

Although CS resulted in a significant increase in lung tissue GPx activity, it had no significant effect on lung tissue SOD activity.

Lipid peroxidation was significantly increased in CS-exposed Guinea pigs as evidenced by the significant increase in lung tissue MDA.

Pretreatment of CS-exposed Guinea pigs with TQ significantly decreased the BALF IL-8, but did not change BALF LTB4 level significantly.

The levels of the inflammatory mediators; NE, TNF-? and MPO, were also significantly reduced after TQ pretreatment.

Although SOD activity was not significantly increased after TQ pretreatment, the overall oxidative status was improved as shown by increased GPx activity and reduced level of MDA in lung tissue homogentes.

Pretreatment of CS-exposed Guinea pigs with EGCG significantly combat the inflammatory consequences of exposure to CS.

This was demonstrated by the significantly reduced levels of IL-8, LTB4, NE, TNF-? (in BALF) and MPO (in lung tissue homogenate).

EGCG also attenuated CSinduced oxidative stress as revealed by the significant increase of GPx activity, and the significant decreased level of MDA in lung tissue homogenates, although SOD activity was not significantly affected.

Conclusion : From this study, it is concluded that TQ (the main active constituent of the black seed) and EGCG ( the major polyphenol in green tea) have protective effects against CS-induced inflammatory and oxidative damage in the guinea pig lungs.

These actions could be attributed, at least in part, to their effects on inflammatory cells, cytokine production, and oxidative stress.

The current results, if extrapolated to humans, would indicate that TQ and EGCG have potential as novel therapeutic agents for COPD patients and could be promising in the design and development of new treatment strategies aiming at limiting cellular inflammatory and oxidative damage.