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Please cite this article as: Aly S, Mahmoud MF, Hassan SHM, Fahmy A, Evaluation of the analgesic activity and safety of ketorolac in whole body fractionated gamma irradiated animals, Future Journal of Pharmaceutical sciences (2015), Abstract:This study was performed to evaluate the analgesic activity and the toxicity of ketorolac in normal and fractionated (1.5 Gy/day/4 days) γ-irradiated animals. Determination of brain serotonin content and serum prostaglandin level were also undertaken. The analgesic activity was tested using formalin test, at three dose levels (15, 30 and 60 mg/kg) after 1 and 7 days post radiation exposure. LD 50 determinations and assessment of liver and kidney function tests were performed. Our results indicated marked analgesic effects on the early and late phases of nociception. Double treatment with ketorolac and irradiation increased brain serotonin content. The acute LD 50 of ketorolac was decreased in irradiated animals as compared to the LD 50 of normal animals. Double treatment with ketorolac and irradiation induced an elevation of gastric mucin content, urea and BUN levels on the 1 st day post irradiation, whereas, albumin level was lowered and globulin level was elevated after 7 days post irradiation. Depending on this study the dose of ketorolac used for treating cancer patients addressed to radiotherapy should be reduced, however, this requires further clinical confirmation.

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.

The current study aims to evaluate the possible neuroprotective impact of gold nanoparticles (AuNPs) and an alpha-lipoic acid (ALA) mixture against brain damage in irradiated rats. AuNPs were synthesized and characterized using different techniques. Then, a preliminary investigation was carried out to determine the neuroprotective dose of AuNPs, where three single doses (500, 1000, and 1500 µg/kg) were orally administrated to male Wistar rats, one hour before being exposed to a single dose of 7Gy gamma radiation. One day following irradiation, the estimation of oxidative stress biomarkers (malondialdehyde, MDA; glutathione peroxidase, GPX), DNA fragmentation, and histopathological alterations were performed in brain cortical and hippocampal tissues in both normal and irradiated rats. The chosen neuroprotective dose of AuNPs (1000 µg/kg) was processed with ALA (100 mg/kg) to prepare the AuNPs-ALA mixture. The acute neuroprotective effect of AuNPs-ALA in irradiated rats was determined against valproic acid as a neuroprotective centrally acting reference drug. All drugs were orally administered one hour before the 7Gy-gamma irradiation. One day following irradiation, animals were sacrificed and exposed to examinations such as those of the preliminary experiment. Administration of AuNPs, ALA, and AuNPs-ALA mixture before irradiation significantly attenuated the radiation-induced oxidative stress through amelioration of MDA content and GPX activity along with alleviating DNA fragmentation and histopathological changes in both cortical and hippocampal tissues. Notably, the AuNPs-ALA mixture showed superior effect compared to that of AuNPs or ALA alone, as it mitigated oxidative stress, DNA damage, and histopathological injury collectively. Administration of AuNPs-ALA resulted in normalized MDA content, increased GPX activity, restored DNA content in the cortex and hippocampus besides only mild histopathological changes. The present data suggest that the AuNPs-ALA mixture may be considered a potential candidate for alleviating radiation-associated brain toxicity.

Introduction: Diabetes is a metabolic disorder of several etiologies, many oral anti-hyperglycemic agents such as sulfonylurea, biguanides are obtainable, but these agents have side effects, thus there is need of a new natural anti-hyperglycemic agent. Methods: The present study was performed to evaluate the protective role of selenium nanoparticles-grape seed extract (SeNPs-GSE) mixture in ameliorating the changes in the oxidative stress biomarkers induced by gamma radiation in diabetic rats. Experimental model of diabetic irradiated rats was induced by single intrapertoneal injection of streptozotocin (STZ 45 mg/kg) followed by γ-radiation exposure (4 Gy). Forty eight rats were randomly classified into 6 experimental groups: normal, diabetic, irradiated, diabetic irradiated, diabetic treated with either SeNPs-GSE mixtureor glimepiride(1 mg) for (14) days followed by γ-radiation. Results: Results of the present study indicated that rats exposed to γ-radiation and, or STZ significantly increase serum glucose& liver MDA levels. This increase was accompanied by a decrease in the levels of serum insulin, total antioxidant (TAC), liver enzyme activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), as well as liver tissue contents of vitamin C (Vit.C) and vitamin E (Vit.E). Diabetic rats treated with (SeNPs-GSE) mixture or glimepiride before γ-radiation exert a significant improvement in all tested biochemical parameters. Conclusion:The present study showed that a mixture of (SeNPs -GSE) possesses antioxidant and anti-diabetic activities by decreasing oxidative stress biomarkers as well as blood glucose level tested in this study. The tested combination (SeNPs-GSE) mixture is more or less equally active as that of the standard tested anti-diabetic drug glimepiride