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Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain

Swamy M, Zakaria AZ, Govindasamy C, Sirajudeen KN, Nadiger HA

Neurosci Res, 2005 Oct;53(2):116-22.
PMID: 16009439

Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects.
Fulltext Effects of Eurycoma longifolia Jack supplementation on eccentric leg press exercise-induced muscle damage in rugby players

Zakaria AZ, Washif JA, Lim BH, Nosaka K

Biol Sport, 2023 Jul;40(3):691-697.
PMID: 37398958 DOI: 10.5114/biolsport.2023.119290

Eurycoma longifolia Jack (ELJ) is a herbal plant that has androgenic and antioxidant effects. We investigated the short-term effect of ELJ supplementation on muscle damage induced by eccentric exercise. Eighteen young (19-25 years), well-trained rugby 7s players were assigned to an ELJ or a placebo (PLA) group (n = 9/group). Each participant took four 100-mg capsules a day for seven days prior to performing a leg press eccentric exercise to failure in a double-blind fashion. Peak force, peak power and jump height in countermovement jump (CMJ), drop jump reactive strength index (RSI), muscle soreness assessed by a 100-mm visual analogue scale, plasma creatine kinase (CK) activity, and salivary hormones were measured at 24 h before and 0.5, 24, 48, 72, and 96 h after the exercise. Changes in the variables over time were compared between the groups by two-factor mixed-design ANOVA. The number of eccentric contractions performed was similar (P = 0.984) between the ELJ (21 ± 5) and PLA groups (21 ± 5). Salivary testosterone and cortisol concentrations did not change (P > 0.05) after the supplementation for both groups. CMJ peak power (-9.4 ± 5.6%) and height (-10.6 ± 4.9%), and RSI (-15.2 ± 16.2%) decreased at 24 h after exercise (P < 0.05), and muscle soreness (peak: 89 ±10 mm) and plasma CK activity (peak: 739 ± 420 IU/L) increased after exercise (P < 0.05) without significant differences between groups. These results showed that 7-day ELJ supplementation prior to the leg press eccentric exercise had no significant effects on hormones, performance and muscle damage markers for the athletes.
Fulltext Cognitive Impairment and Neuropsychiatry Manifestation Following Mild and Moderate Traumatic Brain Injury at 3 Months and 6 Months

Othman A, Idris Z, Rosman AK, Abdullah JM, GhanI ARI, Zakaria AZ

Malays J Med Sci, 2022 Oct;29(5):48-58.
PMID: 36474530 DOI: 10.21315/mjms2022.29.5.6

BACKGROUND: Cognitive impairment (CI) and neuropsychiatry manifestation (NM) are known complications among patients with traumatic brain injury (TBI). However, the clinical correlation between mild and moderate TBI with the above have not been extensively studied.
METHODS: The patients (n = 54) were divided into mild and moderate TBI. Both groups were assessed at 3 months and 6 months post-trauma for the same measures. Diagnosis of CI was done using the Montreal cognitive assessment (MoCA) questionnaire while NM screening was performed using the 12-items General Health Questionnaire (GHQ-12) followed by MINI International Neuropsychiatry Interview (MINI).
RESULTS: We found five patients (19.2%) with mild TBI had CI and five patients (19.2%) had NM at 3 months. Only one patient (3.8%) persistently has CI at 6 months while the rest recovered. As for moderate TBI, 11 patients (39.3%) had CI and seven patients (25%) had NM at 3 months but none had persistent CI or NM at 6 months. Age (P < 0.05) and blood pressure were significant risks (P < 0.05) for CI and NM at 3 months.
CONCLUSION: This study highlighted the importance of screening following mild and moderate TBI at 3 months and 6 months. Early recognition facilitates effective rehabilitation programmes planning hence improve prognosis in the future.

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