Retigabine is a new antiepileptic drug. Its mechanism of action involves activation of voltage gated potassium channel (Kv7, KCNQ). Epilepsy is a disease of chronic nature and may be associated with other diseases that need therapy with other drugs as NSAIDs like diclofenac. Purpose. The current work is designed to study the spectrum of retigabine and diclofenac, on acute seizures in albino mice; also, it investigated the possible interactions between retigabine and diclofenac regarding their anticonvulsant activities and the role of KCNQ channel. Method. Convulsions were induced in mice using the picrotoxin model, the pilocarpine-induced-status epilepticus model, and lastly the maximal electroshock model. Results. The study revealed that combined administration of retigabine and diclofenac significantly increased percentage of protection from convulsions induced by picrotoxin model and MES test. Furthermore, the combination significantly prolonged the mean latency period of convulsion in pilocarpineinduced sustained epilepsy model. Conclusion. we concluded that retigabine has a broad spectrum antiepileptic effect and diclofenac potentiated retigabine action as an opener of potassium (KCNQ2/3) channels.

Amikacin (AK) has the largest spectrum of aminoglycosides. However, its use is constrained because of nephrotoxicity and ototoxicity. Ellagic acid (EA) is a polyphenol present in plants. It has antioxidant, anticarcinogenic, and antimutagenic characteristics. Cilostazol (CTZ) is a phosphodiesterase Ш inhibitor, it is a potent vasodilator and antiplatelet drug. CTZ has an inhibitory effect on reactive oxygen species and superoxide generation in addition to hydroxyl radicals scavenging action. This study determines whether EA and cilostazol have a protective effect against AK-induced nephrotoxicity. Forty-nine rats were divided into seven equal groups: control normal; AK 400 mg/kg; EA 10 mg/kg; CTZ 10 mg/kg; AK 400 mg/kg plus EA 10 mg/kg; AK 400 mg/kg plus CTZ 10 mg/kg; AK 400 mg/kg plus EA 10 mg/kg and CTZ 10 mg/kg. For seven days, drugs were administered using gavage one hour before intramuscular injection of AK. Twenty-four hours after the last AK dosage, blood samples were collected to determine blood urea nitrogen and creatinine levels. Kidneys were removed for histopathological examination and measurement of: malondialdehyde (MDA), catalase (CAT), decreased glutathione (GSH), superoxide dismutase (SOD), interleukin 6 (IL6), tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFκB), and Bcl-2 associated x protein (BAX). AK caused kidney damage, inflammatory mediator elevation, and oxidative stress and apoptotic markers. Rats receiving EA or CTZ indicated significant improvement in kidney function, decrease in oxidative stress and inflammation through NF-kB down-regulation and BAX expression. The combination of EA and CTZ showed a synergistic effect. In conclusion, EA and CTZ might play a beneficial role in preventing nephrotoxicity induced by AK partially by inhibition of tissue inflammation and apoptosis.

Amikacin(AK) has the largest spectrum of aminoglycosides. However, its use is limited due to nephrotoxicity and ototoxicity. Ellagic acid (EA) is a plant phenolic structure. it has antioxidant, anticarcinogenic and antimutagenic properities. Cilostazol (CTZ) is a PDE Ш inhibitor, it is a potent vasodilator and antiplatelet drug. This study aimed to determine if EA and cilostazol have a protective effect against nephrotoxicity caused AK. Forty nine rats were divided into seven equal groups: control normal; AK 400mg/kg; EA 10 mg/kg; CTZ 10mg/kg; AK 400mg/kg plus EA 10mg/kg; AK 400mg/kg plus CTZ 10mg/kg; AK 400mg/kg plus EA 10mg/kg and CTZ 10mg/kg. For seven days, Drugs were given orally one hour before intramuscular injection of AK. After twenty-four hours from the last dosage, samples of blood were obtained to determine blood urea nitrogen (BUN) and creatinine levels in serum, kidneys were extracted and longitudinally divided into two parts, part for measuring the following parameters: malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), interleukin 6 (IL6), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFκB) and Bcl-2 associated x protein (Bax), the other part was placed in formaldehyde solution and examined under light microscopy for routine histopathologic examination. The results of the present study proved that EA, CTZ and their combination protected rats against AK - induced nephrotoxicity; This effect might be a result of the antioxidant, anti-inflammatory and anti-apoptotic properties of these compounds.

Background: Myocardial infarction is a critical complication frequently occurs with type 2 diabetes mellitus (T2DM). Sitagliptin is antidiabetic drug inhibits DPP-4,which augments endogenous level of glucagon like peptide 1(GLP-1).Metformin is an FDA-approved antidiabetic drug, which is commonly prescribed for management of T2DM. Objectives: Is to investigate the possible beneficial effects of sitagliptin, metformin, and their combination on myocardial ischemic and vascular changes in T2D rats and possible mechanisms underlying these effects. Methods: Adult male albino rats were used in this study and were randomly divided into control normal group, control diabetic group , sham diabetic group and diabetic with induction of MI group. Diabetic rats with myocardial infarction(MI) were divided into the following treated subgroups: Oral Sitagliptin (300 mg/kg/day), Metformin(120mg/kg/day) and Combined metformin sitagliptin treated subgroups for 6 weeks. blood glucose (bl gl) level, serum Triglycerides (TG) and Low-density lipoprotein (LDL) levels, markers of oxidative stress(vascular Malondialdehyde (MDA) and cardiac Superoxide dismutase(SOD)levels),inflammation marker(plasma Interleukin-6( IL6),and plasma Creatin kinase-MB (CK-MB) were measured. Hematoxylin and Eosin stained sections of cardiac tissue were examined. vascular reactivity of thoracic aortas were measured. Results:DMT2 with induction of MI evoked oxidative stress, inflammation, as well as histopathological derangements in cardiac tissue and decreased vascular reactivity. Treatment with sitagliptin , metformin and their combination improved the cardiac histopathological changes and vascular reactivity as well as attenuating the oxidative stress and inflammatory processes. Conclusion: Sitagliptin has beneficial protective effects against myocardial ischemic changes induced in T2D rats but combined administration of metformin sitagliptin was superior to each drug alone in cardiovascular protection effects. This protective effect of sitagliptin may be due to its anti-inflammatory and antioxidant potentials.