NG-Nitro-L-Arginine Methyl Ester

Iohexol is a non-ionic contrast agent widely used in diagnostic imaging and angiographic procedures; however, its administration carries the risk of contrast-induced nephropathy. This study was conducted to investigate the ameliorative effects of hesperidin use against iohexol-induced acute kidney injury (AKI) in rats. Male wistar albino rats were randomly assigned into five groups: i) control, ii) hesperidin (100 mg/kg/day orally), iii) iohexol (3 g/kg, i.p), iv) iohexol (3 g/kg) and hesperidin (100 mg/kg) and v) iohexol (3 g/kg) and hesperidin (200 mg/kg). The induction of AKI was performed by dehydration and the administration of contrast media (iohexol) and inhibitors of prostaglandin (indomethacin) and nitric oxide synthesis (L-NAME: N-nitro L-arginine methyl ester). Hesperidin was administered for two weeks before the induction of AKI. Results showed that iohexol induced significant histopathological kidney damage and increased serum urea and creatinine levels. Molecular analyses revealed that iohexol suppressed AQP1 and AQP2 expression, while upregulating KIM-1 and inflammatory markers such as MAPK14, JAK2/STAT3, TRAF6/ACT1/IL-17A, and NFκB/TNF-α/IL-1β at the gene expression level. Furthermore, iohexol decreased the measured activity of antioxidant enzymes (SOD, CAT and GPx) and the GSH content, and significantly increased MDA levels. Additionally, iohexol promoted apoptosis mediated by Caspase-3, Bax, and Bcl-2, and suppressed gene expression of Wnt3a/Dvl-2 and Cyclin D1, which are involved in cell cycle regulation and development. This is the first study to link hesperidin with modulation of Wnt3a/Dvl-2 signaling in iohexol-induced AKI. Hesperidin treatment significantly modulated these parameters, demonstrating a nephroprotective effect. Thus, it was supported that hesperidin could be a potential nephroprotective agent.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amnesia and neuronal network dysfunction. Given that the mediodorsal thalamus (MD) is connected to the medial prefrontal cortex (mPFC), and nitric oxide (NO) signaling is crucial for synaptic plasticity in memory formation, the present study aimed to investigate the role of the MD nitric oxide system in a streptozotocin (STZ)-induced Alzheimer's rat model. Also, the mPFC electrophysiological activity with the local field potential (LFP) was assessed following memory formation under STZ and/or NO agents to evaluate the mPFC interictal epileptiform discharges (IEDs) rate. The results showed that the microinjection of STZ (3 mg/kg/10 μl, 2 times) into the lateral ventricle (LV-STZ) impaired memory formation. Acute intra-MD microinjection of a precursor of nitric oxide, L-Arginine (1.5-6 μg/rat), improved the LV-STZ-induced amnesia. Sub-chronic intra-MD microinjection of an NO system inhibitor, L-NAME (0.5 and 1 μg/rat, 5 times) from the 5th to 13th days after the LV-STZ microinjection, a critical period for producing the neurotoxic effects of STZ on the brain, improved STZ-induced amnesia. Interestingly, the LV-STZ microinjection increased the IEDs in the mPFC, reflecting heightened neuronal hyperexcitability. The manipulation of the MD-NO system was associated with a decrease in the mPFC-IEDs rate, suggesting a negative correlation between the IEDs rate and memory formation. Taken together, these findings highlight the critical role of the MD-NO system in STZ-induced amnesia. Moreover, the dual effects of the MD-NO system manipulation, depending on the context and timing, may counteract STZ-induced amnesia by modulating the mPFC neural activity.