PROTECTIVE EFFECT OF ZILEUTON AND MK-866 AGAINST HEPATIC DAMAGE INDUCED BY DOXORUBICIN

Objective: The present study was designed to investigate the protective effect of Zileuton and MK-886 against hepatic damage induced by doxorubicin. Methods: A total of 30 healthy adult male albino rats were randomized and rats were divided into five groups, six animals in each: Control negative group, Vehicle group: Rats were given ethanol i.p., Dx group: Doxorubicin (15 mg/kg), Mk group: Mk-886-treated rats given 0.6 mg/kg of Mk-886 i.p, and Z group: Zileuton-treated rats given zileuton 10 mg/kg i.p. Biochemical tests of the serum for ASAT and ALAT level were estimated. Serum glutathione (GSH) concentrations (μg/ml) were determined using GSH ELISA Kit, while serum malondialdehyde (MDA) concentrations (ng/ml) were determined using MDA ELISA Kit. Livers were removed from each rat and fixed in 10% neutral-buffered formalin and embedded in paraffin for histopathological studies. Results: MK- and zileuton-treated groups showed higher GSH levels and lower MDA levels as compared with Dx-treated group. MK-886 associated with significant p<0.05 decreased the liver enzymes in comparison with doxorubicin-treated rats. Zileuton showed insignificant (p>0.05) changes. The liver tissues that treated with Dx only showed several histopathological changes such as moderate sinusoidal dilation, vacuolation, mild-to-moderate hepatocyte necrosis/degeneration and inflammatory cell infiltration, and severe congestion. Liver tissues that treated by zileuton with Dx showed sinusoidal dilation, vacuolation, mild congestion, and inflammatory cell infiltration, while those treated with Mk-886 plus Dx showed nearly normal liver pathophysiology. Conclusion: It has been concluded that Zileuton and MK-886 have protective effects against hepatic damage induced by doxorubicin

Antiatherosclerotic Potential of Clopidogrel: Antioxidant and Anti-Inflammatory Approaches

Background. Atherosclerosis is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the walls of large and medium size arteries. Objective. To evaluate the effect of clopidogrel on atherosclerosis progression. Materials and Methods. A total of 28 local domestic rabbits were assigned to four groups: normal control, atherogenic control, vehicle control, and clopidogrel treated. Serum triglycerides, total cholesterol, HDL-C, plasma high sensitive C-reactive protein (hsCRP), plasma malondialdehyde (MDA), and plasma reduced glutathione (GSH) were measured at the end of the experiment. Immunohistochemical of aortic atherosclerotic changes were also performed. Results. There was no statistically significant difference between atherogenic control group and vehicle group. Levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH levels were decreased in animals on atherogenic diet. Immunohistochemical analysis showed that aortic expressions of VCAM-1, MCP-1, TNF-α, and IL-17A were significantly increased in atherogenic control group. Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion. Compared to atherogenic control group clopidogrel do not have significant effect on lipid profile. Clopidogrel significantly reduces hsCRP and MDA levels and increases GSH level. Furthermore, clopidogrel treatment significantly reduced aortic expressions parameters and the histopathologic examination of the aortic arch showed a significant reduction of atherosclerotic lesion. Conclusions. This study outlines how clopidogrel reduces lipid peroxidation, systemic inflammation, and aortic expression of inflammatory markers and hence reduces the progression of atherosclerosis