THE EFFECT OF PRETREATMENT WITH TOLL-LIKE RECEPTOR 4 ANTAGONIST RESATORVID ON METHOTREXATE-INDUCED LIVER INJURY IN RATS: HISTOPATHOLOGICAL STUDY

Objective: This research aims to evaluate the histopathological changes after pretreatment with resatorvid against methotrexate induced-liver injury.Methods: 28 male albino-wistar rats divided into random 4 groups (7 rats in each). Control group: Rats left untreated. Vehicle pre-treated group: Rats were administered dimethyl sulfoxide (DMSO) followed by methotrexate (MTX). Methotrexate treated group: Rats left untreated then administered MTX. Resatorvid pre-treated group: Rats were administered resatorvid followed by MTX. 24 h after the end of treatment, the animals were sacrificed. Liver tissue samples dissected out immediately and fixed in 10% formalin. The traditional procedures (paraffin-embedded method) was used to prepare liver tissue for microscopic evaluation by none alcoholic fatty liver disease (NAFLD) Activity Score Components.Results: Liver tissue sections of MTX-treated group show moderate-to-severe steatosis of hepatic cells and micro- and macro- hepatocellular fatty degeneration and giant fatty cysts with chronic inflammatory cells infiltration. While liver tissue sections of the resatorvid pre-treated group show moderate hepatic cellular fatty degeneration, with a decreased number of fatty cysts chains and the inflammation disappeared.Conclusion: Resatorvid hepatoprotective effect against MTX-induced injury was promising throughout resolving the accompanying inflammation and partial restoring histopathological fatty alterations

Potential Nephroprotectice Effect of Curcumin against Gentamicin Induced Nephrotoxicity : An Experimental Study In Rats

Background: Nephrotoxicity is a serious & common side effect of aminoglycoside and is induced by generation of  reactive oxygen species. Emerging evidence reveals that curcumin possesses antioxidant activity, therefore, this research  was undertaken to evaluate the potential protective effects of curcumin in  amiloration of  nephrotoxicity  induced by gentamicin in male rats.Materials and Methods:Eighteen male Spraque-Dawley rats were included in this study. They were divided randomly into three equal groups (six rats each). Groups I (Control) received  only normal saline i.p, Groups II (GN) received gentamicin (100 mg/kg/day), Group III (GN+CUR) received a combination treatment  gentamicin (100 mg/kg/day, i.p) & curcumin (200 mg/kg/day p.o). The duration of treatment was eight days and at the end of the study, animals were sacrificed and the blood sample was collected for assessment of renal function, blood urea & serum creatinine. Both kidneys were removed and prepared for a histopathology examination.Results:  blood urea and creatinine were significantly higher (P < .05) in gentamycin treated group (group II) as compared to the control group (group I). However, the levels of these parameters in group 3 (co-treatment of gentamicin and curcumin) were significantly lower than those in group 2 (P < .05). Further, the histological score of renal damage was higher in the gentamicin group than in the control group. Combination treatment of curcumin and gentamicin (groupIII) significantly attenuated the histopathological damage.Conclusion: Curcumin attenuated gentamicin-induced renal injury in rats’ models

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

Effect of ferulic acid on Myocardial Ischemia/Reperfusion Injury In Male Mice.

Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia–reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocytes damage.                                                              A total of 24 Swiss albino adult male mice were randomized into 4 equal groups. Group (1) sham group; Group (2) control group; Group (3) control vehicle (DMSO) group; Group (4) Ferulic acid treated group.Results of this study showed that levels of myocardial IL-6, were increased (p<0.001) in the control group. Histologically, all mice  in control group showed significant cardiac injury (p<0.001). Ferulic acid   significantly counteract the increase in myocardium level of IL-6 (P < 0.001). Histological analysis revealed that ferulic acid   markedly reduced (P < 0.001) the severity of cardiac injury in the mice underwent LAD ligation procedure.Keywords: Ischemia-reperfusion (I/R) ,systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS) ,  Ferulic acid (FA), left anterior descending (LAD), Dimethylsulfoxide (DMSO)