The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats.

BACKGROUND AND PURPOSE:

Acute exposure to particulate air pollution has been linked to acute cardiopulmonary events, but the underlying mechanisms are uncertain. EXPERIMENTAL APPROACH We investigated the acute (at 4 and 18 h) effects of diesel exhaust particles (DEP) on cardiopulmonary parameters in mice and the protective effect of thymoquinone, a constituent of Nigella sativa. Mice were given, intratracheally, either saline (control) or DEP (30 µg·per mouse). KEY RESULTS At 18 h (but not 4 h) after giving DEP, there was lung inflammation and loss of lung function. At both 4 and 18 h, DEP caused systemic inflammation characterized by leucocytosis, increased IL-6 concentrations and reduced systolic bloodpressure (SBP). Superoxide dismutase (SOD) activity was decreased only at 18 h. DEP reduced platelet numbers and aggravated in vivo thrombosis in pial arterioles. In vitro, addition of DEP (0.1-1 µg·mL(-1)) to untreated blood-induced platelet aggregation. Pretreatment of mice with thymoquinone prevented DEP-induced decrease of SBP and leucocytosis, increased IL-6 concentration and decreased plasma SOD activity.Thymoquinone also prevented the decrease in platelet numbers and the prothrombotic events but not platelet aggregation in vitro.

CONCLUSIONS AND IMPLICATIONS:

At 4 h after DEP exposure, the cardiovascular changes did not appear to result from pulmonary inflammation but possibly from the entry of DEP and/or their associated components into blood. However, at 18 h, DEP induced significant changes in pulmonary and cardiovascular functions along with lung inflammation. Pretreatment with thymoquinone prevented DEP-induced cardiovascular changes.

3.

Although the state of hyperhomocysteinemia (HHcy) appears to be associated with higher risks of coronary,cerebral and peripheral vascular disease as well as with a number of other clinical conditions, the underlying molecular mechanisms are not fully elucidated. There is strong evidence, however, that HHcy could induce a pathogenic state of oxidative stress. The interest in modulating the elevated levels of total homocysteine in HHcy and/or their negative impacts through preventive strategies, particularly through the supplementation with vitamins that may be linked to the homeostasis of homocysteine (folate, vitamin B(12), and vitamin B(6)), has increased in recent years. Here we show that active antioxidant components of the traditionally used black seeds of Nigella sativa plant protect against the development of methionine-induced HHcy and its associated state of oxidative stress. Pretreatment of rats with an oral dose of 100 mg/kg of thymoquinone, the main active constituent of the black seed, for 30 min and for 1 week almost completely protected against induced HHcy measured 5 h after methionine load (100 mg/kg). Under similar conditions pretreatment with commercial black seed oil (100 microl/kg) for 30 min and for 1 week produced significant and strong protection levels of 74.2 and 94.5%, respectively. Under the state of induced HHcy there were significant increases in the plasma levels of triglycerides, lipid peroxidation, cholesterol and in the activities of glutathione peroxidase and superoxide dismutase. Catalase activity was not affected. The total antioxidant status, however, was significantly depressed. All of these effects were almost totally blocked by prior treatment with thymoquinone or black seed oil. These findings may contribute towards a protective measure utilizing the black seed against the negative impacts of HHcy.