Background: 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. Aim: This study was aimed to investigate the possible interactions between phenytoin and rosuvastatin when used together in irradiated rats. Methods: 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 & ALT) and oxidative stress biomarkers (MDA, NO & SOD). Results: 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 & 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.
Tamoxifen-induced hepatotoxicity is an inevitable side effect during breast cancer treatment. Low-dose gamma irradiation (IRR) shows many beneficial effects by stimulating various biological processes. This study evaluates the possible effect of sildenafil and low-dose gamma radiation on liver damages as new treatment strategies.Group I (control), group II: (tamoxifen), group III: (tamoxifen + Sildenafil), group IV:(tamoxifen+ irradiation) and group V: (tamoxifen +Sildenafil + irradiation). Rats were sacrificed after 5 h from tamoxifen injection. Results showed that tamoxifen caused elevation in serum AST, ALT and ALP as well hepatic ROS, iNOS, MDA, Keap-1 and NF-Kb, in addition to diminution in hepatic Nrf2 and HO-1. Exposure to low-dose gamma radiation and sildenafil amended the alterations in the measured parameters in serum and tissue. Moreover, all results were confirmed by histopathological examination. In conclusion, sildenafil and low-dose gamma radiation can mitigate the toxicity induced by tamoxifen in liver tissues. Hence, this treatment could be further evaluated as a new approach for alleviating various liver disorders.
Purpose The present study investigates the new approach of rosuvastatin (RUV) administration as a drug for the management of spleen injury induced by gamma irradiation. Main Methods Forty rats were used and divided equally into 4 groups: control group, irradiated group, IRR + rosuvastatin group (10 mg/Kg b. wt), and IRR + rosuvastatin group (20 mg/kg b. wt) for 7 days orally. Results The possible curative effect can be illustrated via the improvement of hematopoietic cell count (Hb, RBCs, and WBCs) and oxidative stress markers (MDA and GST) in addition to biochemical parameters including [heme oxigenase-1 (HO-1), nuclear erythroid 2-related factor (Nrf2), NOD-, LRR- and pyrin domain- containing protein 3 (NLRP3) inflammasome] and immune assay of nuclear factor kappa beta (NF-kB P65) and inducible nitric oxide synthase (iNOS). Histological pictures emphasize the biochemical findings. Rosuvastatin treatments by using two different doses improve the tested parameters. High-dose administration of RUV (20 mg/kg p.o.) recorded better results than the low dose (10 mg/kg p.o.). Conclusion Our results suggested that rosuvastatin reversed the radiation-induced spleen-damaging effects. So, RUV can be introduced to the market as a new therapy for the management of spleen damages.
Drug interactions between phenytoin and rosuvastatin may occur when used together in normal rats, so the present study was conducted to investigate the effects of the individual as well as combined drugs were studied in normal rats. Rats were divided into 4 groups namely: normal control, phenytoin (60 mg/kg i.p.), rosuvastatin (1.25 mg/kg i.p.) or combination of both phenytoin and rosuvastatin, respectively. Data of the present work revealed that, phenytoin increased serum total cholesterol. Rosuvastatin didn't affect serum total cholesterol or serum triglycerides. Combination increased serum total cholesterol but it didn't affect serum triglycerides. Phenytoin significantly increased serum LDL-C. Rosuvastatin had no effect on serum HDL-C, serum LDL-C and VLDL-C levels. Combination didn't change serum lipoproteins (HDL-C, LDL-C and VLDL-C). Individual drugs or their combination had no effect on risk factor and atherogenic index. Phenytoin significantly increased serum ALT level. Rosuvastatin had no effect on serum AST and serum ALT levels. Combination significantly increased serum AST level. Phenytoin significantly increased serum MDA level but it had no effects on serum NO level and blood SOD activity. Rosuvastatin significantly increased serum NO level. Combination significantly increased serum NO level, so Combination of phenytoin and rosuvastatin has a good effect on oxidative stress by increasing serum NO level. In conclusion, the results revealed that, there are drug interactions between phenytoin and rosuvastatin. The interactions improve liver functions and lipid peroxidation. A part from the action of the combination on total cholesterol, it improves lipid profile.
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