Drug interactions between phenytoin and rosuvastatin on lipid profile, liver functions and oxidative stress biomarkers in irradiated rats

Phenytoin is one of the most commonly used anticonvulsants for treating generalized tonic-clonic seizures and status epileptics. Rosuvastatin is a new generation HMG-CoA reductase inhibitor. This enzyme converts HMG-CoA to mevalonic acid in the cholesterol biosynthetic pathway which is the rate limiting step in cholesterol synthesis. This study was aimed to investigate the possible interactions between phenytoin and rosuvastatin when used together in irradiated rats. The experiments were carried out to investigate the acute effect of each drug individually and in combination with radiation on lipid profile [Total cholesterol, Triacylglycerols, High density lipoproteins, Low density lipoproteins and Very low density lipoproteins, Risk factor, Atherogenic Index], liver function tests [AST and ALT] and oxidative stress biomarkers [MDA, NO and SOD]. Data revealed that, phenytoin in irradiated rats significantly increased serum total cholesterol compared to normal control. Rosuvastatin significantly decreased serum total cholesterol compared to irradiated control. Combination of two drugs significantly increased serum total cholesterol; triacylglycerols and serum VLDL-c levels compared to normal and irradiated rats and significantly increased Atherogenic Index and Risk factor compared to normal control. Phenytoin significantly increased serum ALT level compared to normal and irradiated rats and significantly increased serum MDA and serum NO levels compared to normal rats. But phenytoin significantly decreased MDA and NO levels and significantly increased SOD activity compared to irradiated rats. Rosuvastatin significantly increased serum ALT level compared to normal control but it significantly decreased MDA and significantly increased SOD activity compared to irradiated rats. Combination phenytoin and rosuvastatin in irradiated rats significantly increased serum ALT level compared to normal and irradiated rats and it significantly increased MDA, NO levels but it significantly decreased SOD activity compared to normal control. It could be concluded that administration of phenytoin concurrently with rosuvastatin not recommended in patients receiving radiotherapy as dangerous side effects may be occurred

Protective effects of onion oil and selenium against cisplatin-induced nephrotoxicity and oxidative stress in rats

Nephrotoxicity is an inherent of certain anticancer drugs. This study aimed to assess the protective effect of onion oil and selenium against cisplatin-induced nephrotoxicity in male rats. Cisplatin [5 mg/kg, i.p.] caused significant increases in serum sodium, blood urea nitrogen, serum creatinine, total sodium and potassium excreted in urine, urine volume and lipid peroxides measured as the malondialdehyde content of kidney, with significant decreases in serum total protein, creatinine clearance, reduced glutathione content of kidney and kidney superoxide dismutase activity as compared to the control group. On the other hand, administration of onion oil [100 mg/kg, p.o.] or selenium [1 mg/kg, p.o.] for 14 days with a single cisplatin dose on the 10[th] day ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress biomarkers. Onion oil and selenium showed protective effects against cisplatin-induced nephrotoxicity

Protective effects of amlodipine, coenzyme Q10 and their combination on myocardial ischemia/reperfusion injury in rats

Ischemia/reperfusion [I/R] injury is of major clinical relevance during ischemic heart diseases, percutaneous transluminal angioplasty, coronary artery bypass and heart transplantation. Amlodipine, a calcium channel blocker, exhibits antioxidant and antiproliferative activities as well as eNOS activation that could help in cardioprotection following I/R insult. Coenzyme Q10 [CoQ], a mitochondrial coenzyme involved in oxidative phosphorylation, possesses strong antioxidant and lipid peroxyl neutralizing functions. The current study demonstrated the possible cardioprotection of amlodipine [15 mg/kg/day] and CoQ [200 mg/kg/day] alone or in combination against myocardial I/R-induced functional, metabolic and cellular changes. Drugs were administered orally for one week. Rats were then subjected to myocardial I/R [35min/10min]. Heart rates and incidence of ventricular arrhythmias were recorded during l/R progress. At the end of reperfusion, blood samples were collected for estimation of plasma creatine kinase [CK] activity. The left ventricle homogenates were used for determination of lactate, ATP, thiobarbituric acid reactive substances [TBARS], reduced glutathione [GSH] and total nitrate/nitrite [NOx] contents as well as myeloperoxidase [MPO] activity. Finally, histological examination was performed to visualize the possible cellular effects of the drugs. Amlodipine, CoQ and their combination significantly protected against reperfusion-induced tachycardia and decreased the incidence and severity of arrhythmias. Amlodipine afforded a significant degree of protection against plasma CK elevation and myocardial GSH depletion, while it completely protected against myocardial MPO, lactate and TBARS elevation. On the other hand, it failed to defend against ATP depletion and NOx elevation. CoQ provided a significant degree of protection against plasma CK, myocardial MPO, NOx elevation and ATP depletion. It completely protected against GSH depletion, lactate and TBARS elevation. Combination therapy provided significant increase in myocardial ATP and GSH contents and significant decrease in plasma CK activity in comparison with amlodipine monotherapy. It could be concluded that adding CoQ to amlodipine therapy offered remarkable improvement in the cardioprotective effect of amlodipine