---

Background & Objective: In this research, we study the simultaneous effects of Nitric Oxide (NO) and stress on prefrontal cortex of rats. Nitric Oxide is an unstable small molecule that involved in many physiological and pathological conditions. Brain’s prefrontal cortex has important role on personality and mental state. Its development continues after birth and this period is the most sensitive time for brain’s cortex to response to environmental parameters such as psychological stresses. Materials & Methods: In this study Wistar male rats received L-arginine (200 mg/kg) as NO precursor, L-NAME (20mg/kg) and 7-nitroindazole (25mg/kg) as non specific and specific NO sentries inhibitors. L-arginine and L-NAME were injected intra peritoneal (IP) and 7-nitroindazole injected subcutaneously (S.C) during one month per day. Rats divided in two groups (with stress and without stress). The kind of stress was immobilization every day for one month during injection of materials. Brains were removed after this period and each brain with a coronal section manner divided in two parts .Anterior part of brain fixed by formalin and tissue processing was done. By using rotatory microtome 10? serial cross sections were obtained and stained with H & E. Posterior part of brain homogenized with such solution then amount of NO in obtained solution was measured by spectrophotometer with 540 nm wavelength. Results: Statistical analysis of light microscopic findings indicated that stress of immobilization with use of L-NAME and 7-nitroindazole result in decrease of thickness of prefrontal cortex , numbers of Betz cells and NO production in rats’ brain, it means L-NAME and 7-nitroindazole exaggerate the brain damage and from other hands L-arginine with stress can convert these results. Conclusion: On the basis of these results we believe that stress of immobilization damages prefrontal cortex and also NOS inhibitors can aggravate the cortical damage. On the other hand although NO precursor (L-arginine) decreases the cortical damage in rats that impress with stress, it can result in these changes in rat’s brain without stress.

---

Background & Objective: Many evidence indicated that action of glucocorticoid receptors can modulate anxiety behaviors and these effects probably mediated by nitric oxide (NO) system. Thus, in this study, we investigated interaction between corticosterone and NO on anxiety behaviors in mice in elevated plus maze (EPM).

Materials & Methods: In this experimental study male albino mice (25-30 g) were used. A standard EPM was used to determine anxiety behaviors. Two behavioral measures were used that include of the percentage of time spent in the open arms and the ratio of open arm entries to total entries during 5 min. Animals received IP injection of L-Name 30 mg/kg as an inhibitor or L-Arginine 50 mg/kg as a synthesis of NO or saline 60 min and corticosterone (1, 2.5, 5 mg/kg) 30 min before of evaluation.

Results: Analysis of data indicated that corticosterone at doses of 1 and 2.5, but not 5 mg/kg significantly reduced anxiety behavior in mice (P<0.05). Also pretreatment of L-Name potentiate but injection of L-Arginine had inhibition of corticosterone effects (P<0.05).

Conclusion: This study revealed that glucocorticoid induces anxiolytic effects and these effects probably potentiate by NO inhibitor and reduced by NO synthesis. Therefore, it seems that there are interaction between of glucocorticoid and NO system for control of anxiety behaviors.

---

Background and Objective: Nitric oxide synthase (NOS) paly a role in nitric oxide (NO) generation. Despite the beneficial effects of NO on different body systems its overproduction of produce reactive nitrogen species (RNS) and nitrosilation of proteins. This study was done to evaluate the effect of asymmetric dimethylarginine (ADMA) and NG-Monomethyl-L-arginine methyl ester (L-NMMA) on inhibition of nitric oxide synthase activity. Materials and Methods: In this laboratory study, Nitric oxide synthase was extracted from 500 grams of sheep kidney by homogenization, ammonium sulphate precipitation and column chromatography on DEAE-32 Cellulose and 2', 5'-ADP-agarose. During purification, protein content was measured according to the Bradford and enzyme activity was assayed using the Griess reactions the inhibitory effects of 25 μΜ concentrations of ADMA and L-NMMA on purified enzyme were determined. Results: Specific activity and yield of NOS were 0.6 units/mg protein and 0.9%, respectively. Molecular weight of purified enzyme was 54 KD with SDS-PAGE. ADMA and L-NMMA in 25 μΜ concentrations reduced enzyme activity by 76 and 61.2%, respectively. Km values for NOS in absence and in presence of ADMA and L-NMMA were 5.32 μM, 31.25 μM (P<0.05) and 14.29 μM (P<0.05), respectively. Vmax for NOS in absence and presence of inhibitors was not changed. Conclusion: ADMA and L-NMMA have competitive inhibitory effect on NOS activity and ADMA have higher inhibitory effect than L-NMMA.

---

Background and Objective: Due to high metabolic activity and rich blood supply, the kidneys are exposed to high levels of reactive oxygen species (ROS) under pathological conditions, making them highly vulnerable to oxidative stress. Nephrotoxic agents, such as cisplatin, aminoglycosides, and radiocontrast agents induce the production of ROS in renal tubular cells, leading to lipid peroxidation, protein oxidation, and mitochondrial dysfunction. This study was conducted to determine the protective effect of L-arginine against amikacin-induced nephrotoxicity in normal African green monkey kidney epithelial cells (Vero) by evaluating oxidative stress parameters.
Methods: This descriptive-analytical in vitro study was conducted on Vero cell lines purchased from the National Genetic Resources Cell Bank. For all assays, the amount of cultured calls was 10⁵. Prior to the induction of nephrotoxicity with amikacin (653.2 µg/mL), the cells were pre-treated for 24 hours with various concentrations of L-arginine (108, 216, 430, and 860 µM). Subsequently, to evaluate the effect of L-arginine on oxidative stress status, the variables of malondialdehyde (MDA), cell viability, and ROS were measured.
Results: In the assays for ROS levels and cell viability, all tested concentrations of L-arginine (108, 216, 430, and 860 µM) resulted in a significant reduction in ROS levels (30±1.5, 28±1.4, 25±1.2, and 21±1.0, respectively) and a significant increase in cell viability (55±5.2, 64±3.8, 72±2.9, and 84±4.7, respectively) (P<0.05). Regarding measurement tests of lipid peroxidation, L-arginine at 108 µM did not significantly reduce MDA levels; however, other concentrations (216, 430, and 860 µM) significantly decreased MDA levels to 0.80±0.02, 0.74±0.03, and 0.66±0.01, respectively (P<0.05).
Conclusion: The findings of this study demonstrate the ability of L-arginine to improve kidney cell viability parameters and increase glutathione (GSH) levels at all tested concentrations (108, 216, 430, and 860 µM). Furthermore, L-arginine at concentrations of 216, 430, and 860 µM significantly reduced lipid peroxidation.
 

---

Background and Objective: Impairment in nitric oxide (NO) production can culminate in pathological conditions, such as pulmonary hypertension, acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). The present study aimed to investigate the effects of L-arginine and L-nitro-arginine methyl ester (L-NAME) on the diameter and number of pulmonary alveoli in female rats.
Methods: In this experimental study, 32 female Sprague-Dawley rats, aged 8 weeks and weighing 200–250 g, were randomly divided into four groups of eight. Group 1 received normal saline (2 ml/kg body weight [BW]), Group 2 received L-arginine (200 mg/kg BW), Group 3 received L-NAME (20 mg/kg BW), and Group 4 received a combination of L-arginine (200 mg/kg BW) and L-NAME (20 mg/kg BW) via intraperitoneal injection for two weeks. The animals were then anesthetized, and their lungs were excised. After fixation and tissue processing, histological sections were stained with hematoxylin and eosin (H&E) to evaluate the resulting changes. To obtain quantitative data regarding the diameter and number of alveoli, ImageTool III software was utilized.
Results: Injection of L-NAME and L-Arginine led to a non-significant decrease in the mean diameter of pulmonary alveoli. L-Arginine exerted the greatest effect and L-NAME had the least effect on the number of pulmonary alveoli; however, these changes were not statistically significant.
Conclusion: Injection of L-Arginine and L-NAME had no significant effect on the diameter and number of pulmonary alveoli in female rats.

---

Background and Objective: High-intensity interval training is highly effective for improving athletic performance. However, the substantial mechanical and metabolic stress associated with this training may cause considerable post-exercise inflammation and transient biochemical disturbances. This study aimed to compare the effects of six weeks of high-intensity interval training combined with L-arginine supplementation on interleukin-6, interleukin-10, and liver enzyme levels in soccer players.
Methods: This clinical trial included 20 volunteer semiprofessional soccer players in Mashhad during 2025. Participants were allocated by simple randomization to either an exercise-plus-supplement group or an exercise-plus-placebo group. The six-week intervention consisted of three high-intensity interval-training sessions per week. Blood samples were collected at two time points (pretest and posttest), both at 8:00 a.m. after a 12-hour fast. Cytokine concentrations were measured by enzyme-linked immunosorbent assay, and the liver enzymes ALT and AST were measured using standard photometric methods and an autoanalyzer.
Results: At posttest, the exercise-plus-supplement group showed a statistically significant increase in interleukin-10 and a statistically significant decrease in alanine aminotransferase compared with the placebo group (P<0.05). Within-group comparisons showed a statistically significant reduction in interleukin-6 in the exercise-plus-supplement group (P<0.05), whereas no significant change occurred in the exercise-plus-placebo group. Interleukin-10 increased significantly by the end of the intervention in the exercise-plus-supplement group (P<0.05), but did not change significantly in the exercise-plus-placebo group. Aspartate aminotransferase and alanine aminotransferase decreased significantly in the exercise-plus-supplement group (P<0.05), whereas neither enzyme changed significantly in the exercise-plus-placebo group.
Conclusion: Exercise combined with L-arginine supplementation significantly increases interleukin-10 and reduces interleukin-6 and liver enzyme levels.