SUMMARYPurpose: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy. Methods: Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/ day). Key Findings: When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ. Significance: This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration.
Recent years have shown considerable efforts to identify new chemopreventive agents that could be of clinical value. In the current study, modulatory effect of Nardostachys jatamansi (Jones) DC on benzoyl peroxide-induced oxidative stress, toxicity, and ear edema is investigated. Pretreatment with jatamansi at doses of 2.5 and 5 mg=kg body weight in acetone prior to the application of benzoyl peroxide (20 mg=animal per 0.2 ml acetone) resulted in significant inhibition of benzoyl peroxide-induced cutaneous oxidative stress, toxicity, and ear edema in a dose-dependent manner. The cutaneous microsomal membrane lipid peroxidation and xanthine oxidase activities were significantly reduced (p < 0.05). Moreover, the depleted levels of phase II metabolizing enzymes and glutathione were recovered significantly (p < 0.05). Our findings suggest that N. jatamansi is an effective chemopreventive agent in mouse skin with potential of ameliorating benzoyl peroxide-induced cutaneous oxidative stress, toxicity, and ear edema.
A new, simple, rapid, accurate and precise HPTLC method was developed. The detector response was linear for concentrations between 100-600 ng/spot (r =0.9931). The limits of detection and quantitation were 25 ng/spot and 75 ng/spot, respectively. The recovery study was carried out by standard addition method and was found to be 99.60±0.27. Statistical analysis proved that the method was precise, accurate and reproducible, and hence was suitable for the routine analysis of artemisinin.
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