Modulatory effect of thymoquinone and epigallocatechin gallate on cigarette smoke-induced oxidative stress and inflammatoryresponses in guinea PIGS

Cigarette smoke [CS] is implicated in many pulmonary disorders. This may be explained on the ground of airway inflammation, and increased levels of reactive oxygen species [ROS] in airways and lungs. Many drugs have been used aiming at protecting smokers of the consequences of cigarette smoking, but with limited success. 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 ofNigella sativa seeds and [-]-epigallocatechin-3-gallate [EGCG], the major poly phenol isolated from green tea were investigated for their possible modulatory effects on lung responses to CS. Guinea pigs were exposed to the whole CSfor 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 b.w.] treated group, and EGCG [2 mg/kg b.w.] treated group. Markers of inflammation [IL-8, LTB4, NE, and TNF-alpha] were assayed in bronchoalveolar lavage fluid [BALF] from those animals. Lung tissue homogenate were assayed for myeloperoxidase [MPO] activity and markers of oxidative stress [SOD, GPx and MDA]. CS induced significant lung inflammation as evidenced by increased IL-8, LTB4, NE, TNF-a and MPO in BALF and lung homogenate. Although CS induced lung tissue GPx activity, with no effect on SOD, the level of lipid peroxidation was significantly increased. Pretreatment with TQ significantly decreased the chemoattractant agent IL-8 but not LTB4 level. The level of the inflammatory mediators; NE, TNF-alpha and MPO, were also significantly reduced. Although the SOD activity was not significantly increased, the overall oxidative status was improved as shown by increased GPx activity and reduced level of MDA in lung tissues. Pretreatment 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-alpha and MPO in BALF and lung homogenate. EGCG attenuated also CS induced oxidative stress as revealed by significant increase of GPx activity, and decreased levels of MDA in lung tissues, although SOD level was not affected. From this study, it may be concluded that TQ and EGCG, have protective effects against CS induced inflammatory and oxidative damage in guinea pig lungs, which could be attributed, at least in part, to their effects on inflammatory cells, cytokine production, and attenuation of lipid peroxidation

possible antifibrotic effect of theophylline, diltiazem, deferoxamine and minoxidil on the development of murine schistosomal hepatic fibrosis

The effects of theophylline, diltiazem, deferoxamine and minoxidil with and without praziquantel [PZQ] were tested on Schistosoma mansoni infected mice to investigate their possible effect on the progression of hepatic granulomatous reaction into fibrosis in murine schistosomiasis. 66 male Swiss strain albino mice were used in the study. They were divided into 4 groups; control group; infected and treated with PZQ [1000 mg/kg/day] orally for two successive days; infected and treated for 2weeks with deferoxamine [25 mg/kg/day], diltiazem [24 mg/kg/day], theophylline [30 mg/kg/day], or minoxidil [1.0 mg/kg/day]; infected and treated with each of the previous drugs combined with PZQ. At the 10[th] week postinfection, animals were subjected to splenic pulp pressure measurement. The pathological changes in the liver were examined by routine H and E and Masson Trichrome stains. Livers were examined for egg count, granulomas number and size. Liver collagen deposition was also determined. Statistical correlation of the results was done. Praziquantel significantly reduced liver egg count, granulomas number and size. It decreased liver fibrosis assessed histopathologically, liver collagen content and portal venous pressure but not to significant levels. None of the tested drugs [deferoxamine, theophylline, diltiazem, or minoxidil] succeeded to reduce schistosoma egg deposition or granulomas number and size in livers of schistosoma-infected mice. However, significant reduction in these parameters was achieved only when PZQ was added to the treatment regimen. Deferoxamine, theophylline, and minoxidil significantly decreased level of hepatic fibrosis, collagen deposition and portal venous pressure. These effects were significantly augmented when PZQ was combined with any of these drugs. Diltiazem alone or in combination with PZQ failed to decrease liver collagen content or hepatic fibrosis induced by schistosoma infection. However, diltiazem alone or in combination with PZQ could significantly reduce portal venous pressure. Accordingly, it is recommended to extend this animal study to human to investigate the possible mitigation of the deleterious effects of schistosomiasis on the liver by the addition of deferoxamine, theophylline, or minoxidil to its treatment regimen. Diltiazem can also be used to reduce portal venous pressure