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

Gamma irradiation-induced early gastrointestinal disturbances: role of cystamine as a protective agent

The effect of the lethal dose [8 Gy] of whole body gamma irradiation on the early gastrointestinal disturbances in rat was investigated in- vivo as well as in-vitro. Results of the in-vivo study revealed that an early, almost immediately, progressive increase in the weight of the stomach contents as well as marked increase in the intestinal motility were detected during the first 6 hours post irradiation. Results of the in-vitro study showed alterations in the spontaneous contractions of the isolated intestine of the rat. The irregular contraction pattern characteristics of jejunal segments isolated from non-irradiated [control] rat was changed to a more regular pattern 1, 3 hours as well as one day after gamma-irradiation. Administration of Cystamine [50 mg/kg] prior to gamma irradiation [8 Gy] produced a good radiaprotective effect and ameliorated the effect of gamma-irradiation on the stomach. Besides, it normalized the disturbed intestinal movements. In conclusion, the present study suggests the application of Cystamine as a promising start for its trial in clinical radiotherapy especially for patients undergoing abdominal radiotherapy

Imidazole protects the cardiovascular and respiratory systems against whole body gamma-irradiation "an experimental study"

The radioprotective effect of imidazole on the blood pressure, heart and respiratory rates was investigated in adult male rats. Whole body gamma-irradiation at a dose level of 6 Gy. exerted a significant hypotension and tachycardia after one and seven days post gamma-irradiation. There was a significant decrease in respiratory rate after one day of irradiation, but, a significant increase after 7 days, post-irradiation. Administration of imidazole [350 mg/kg] did not significantly affect the blood pressure, but significantly increased heart and respiratory rates after one and seven days of imidazole administration. Imidazole [350 mg/kg] 5-15 minutes before whole body, gamma-irradiation at a dose level of 6 Gy. significantly antagonised the effect of gamma-irradiation on blood pressure, heart and respiratory rates. Meanwhile imidazole completely abolished the effect of gamma-irradiation on the respiratory rate, but it did not completely abolish the effect on the blood pressure and heart rate. The results of the present investigation indicate that imidazole [350 mg/kg] is a good protector against gamma-irradiation induced changes on blood pressure, heart and respiratory rates