Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12±0.05 µmol/min/100 g) and misoprostol+celecoxib groups (0.07±0.02 µmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65±0.02 vs. 0.35±0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61±0.06 vs. 0.37±0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol.

No abstract

No abstract

No abstract

Methylphenidate (Ritalin®, MPH) is a psychostimulant that increases the levels of catecholamine neurotransmitters in the synaptic cleft by blocking reuptake through the dopamine transporter (DAT) and the norepinephrine transporter (NET). Although MPH is commonly used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), relatively little is known regarding the consequences of long‐term exposure to this drug. In this study, we investigated the effect of long‐term MPH exposure on the rate of neurogenesis in the hippocampus. Briefly, 25 day old male mice received intraperitoneal injections of saline, 1mg/kg, or 10mg/kg of MPH twice‐daily for 28 days. On day 29, the mice were injected with 5‐ethynyl‐2′‐deoxyuridine (EdU), a modified nucleoside used to identify newly generated cells. Brain tissue was collected 1 day post EdU injection to determine neurogenesis rate and 28 days post EdU injection to examine the survival of newly generated cells. Brain tissue was sectioned on a cryostat, and tissue sections were stained using a Click‐iT® EdU Imaging Kit and double‐labeled using immunohistochemistry for the neuronal marker, NeuN. Stained cells in the dentate gyrus were counted using an epifluorescence microscope, and the ratio of EdU positive cells to NeuN positive cells were compared between groups. Funded by the ETSU Research Development Committee and the Department of Pharmaceutical Sciences