Protective Role Of L-arginine Research Articles

Effect of induced hepatic ischemia–reperfusion on the adrenal cortex of adult male albino rats and the possible protective role of L-arginine: Biochemical, histological and immunohistochemial study

Hepatic ischemia reperfusion injury (IRI) takes place through liver transplantation. Hepatic IRI might seriously affect liver function and is reported to be accountable for 15 % of organ failure and could result in multi-organ dysfunction syndrome (MODS) that lead to high rates of morbidity and mortality. L-arginine (L-Arg) could reduce hepatic IRI via different mechanisms Objective: To estimate the effect of hepatic ischemic reperfusion (I/R) and the possible protective effect of L-Arg. on the adrenal cortex. Materials & Methods: Thirty two albino rats were utilized in the current work. The animals split to Sham-Operation, L-Arg , ischemic reperfusion, I/R group and I/R and L-Arg group. Then, at the assigned time, blood samples were assembled for biochemical study. Histological and immunohistochemical studies were performed on the adrenal tissueResults: The adrenal cortex of I/R group exhibited architecture loss of the three zones. Zona glomerulosa cells showed small pyknotic nuclei and vacuolated cytoplasm. Zona fasciculata cells appeared ballooned with small pyknotic nuclei. Also, karyolitic nuclei were seen. zona reticularis cells showed pyknotic nuclei and vacuolated cytoplasm and separated by congested blood sinusoids. Hyaline material depositions were seen. Biochemical study revealed a marked increase in serum levels of liver enzymes, excess in the MDA level and a marked reduction in the CAT level compared to control group. These changes were ameliorated by L-Arg.Conclusion: hepatic I/R has been proved to induce histological changes of the adrenal cortex which could be ameliorated by administration of L-Arg. Therefore, For inhibiting or reducing hepatic IRI through liver surgery, an effective method is urgently required.

Alterations in Kidney of Albino Rat due to Acrylamide Exposure and the Possible Protective Role of l-arginine (Biochemical, Histological, Immunohistochemical and Molecular Study)

Acrylamide (ACR): is an industrially conjugated reactive molecule that initiates cellular toxicity, induced oxidative stress and classified as a probable human carcinogen. L-arginine (L-Arg) produces nitric oxide (NO): that involved in vascular regulation, immune activity, and able to eliminate intracellular pathogens. This work conducted to evaluate nephrotoxicity of ACR and the possible protective role of L-Arg at biochemical, histopathological, immunohistochemical and molecular levels. Forty male rats were divided equally into four groups; control: received the ordinary water and diet. ACR: Animals were given a dose of ACR (50mg/kg/day): dissolved in water. ACR + L- Arg: Animals given the same dose of ACR together with L-Arg dissolved in water. L-Arg: Animals administered L-Arg by a dose of 200 mg/kg/day dissolved in water. The exposure period was a month. Kidneys were removed and prepared for histopathological, immunohistochemical studies (caspase3). Also, kidney specimens taken for real-time-PCR technique to measure p53 expression and comet assay. Blood samples were collected for kidney function detection. Animals exposed to ACR showed several histopathological lesions including glomerular shrinkage, loss of PCT brush borders, degeneration of renal epithelia, deposition of hyaline casts and necrotic areas in the renal parenchyma. significant increase in p53 expression, significant increase in caspase 3 activity in renal cells and increase in creatinine levels. However, urea levels recorded a significant decrease. Animals treated with L-Arg together with ACR showed a marked improvement in all these parameters towards the normal status. The study suggested that the administration of L-Arg provided a protective potential against ACR-nephrotoxicity.

Chromosomal Aberrations Due to Acrylamide Exposure and The Protective Role of L-arginine in Bone Marrow Cells of Male Albino Rats.

Acrylamide (Acr) is a human carcinogen which generated in foodstuffs rich with carbohydrates during overheating. It has been recorded to induce carcinogenic and genotoxic effects in experimental animals. So, the present work aimed to evaluate the genotoxic effect of Acr and the possible protective role of L-arginine (amino acid) against Acr genotoxicity using the chromosomal aberration assay in male albino rats (Rattus norvegicus). In the current investigation, 20 male albino rats were equally divided into four main groups (n = 5); Group1 (control): Animals were received the ordinary water and diet. Group2 (L- arginine): Animals were given L- arginine at a dose of 200mg/kg/day for a month by oral gavage. Group3 (acrylamide): Animals were given Acr at a dose of 50mg/kg/day for a month by oral gavage. Group4 (Acrylymide+ L-arginine): Animals were given Arc (50mg/kg/day) together with L-arginine (200mg/kg/day) for a month by oral gavage. The results of the present work concluded that Acr is a genotoxic agent, it induced a significant increase in the frequency of total chromosomal aberrations (numerical and structural). L-arginine provides a protective potential against genotoxicity induced by Acr and this was supported by a significant reduction in the frequency of chromosomal aberrations although, the value remained higher and significant as compared with control group.

Protective Role of L-arginine on the Suprarenal Gland of Adult Male Albino Rats Subjected to Recurrent Acute Restraint Stress: A Histological and Immunohistochemical Study

ABSTRACTBackground: The adrenal glands are small flattened glands closely applied to the upper pole of each kidney. The adrenal cortex consists of three layers that vary primarily in the arrangement of the secretory cells comprising each layer. The gland adapts to various forms of acute and chronic stress. Nitric oxide (NO) is an important endogenous biological modulator, produced by various cell types in different tissues and has diverse physiological actions, including the modulations of vascular resistance, tissue perfusion, blood pressure, and cell proliferation. L-arginine is one of the most metabolically versatile amino acids. In addition to its role in the synthesis of nitric oxide, L-arginine serves as a precursor for the synthesis of polyamines, proline, glutamate, creatine, agmatine and urea.Aim of work: To study the microscopic changes that might occur in the suprarenal gland of adult male albino rats in response to recurrent episodes of acute restraint stress and the role of L-arginine in relieving or blocking these changes.Material and Methods: Thirty adult male Albino rats, 200 - 250 gm body weight each, were used in the present study. The rats were divided into three groups (ten rats/group). Group I: Control group: were not exposed to stress and allowed to move freely. Group II: Rats subjected to recurrent episodes of acute restraint stress: rats were exposed to immobilization stress. The fore limbs and hind limbs of rats were tied separately and then together securing them with adhesive tape thereby immobilizing them for 2 hours daily for 7 days. Group III: Rats treated with L-arginine and subjected to recurrent episodes of acute restraint stress: rats were administered L-arginine by gastric gavage, at a dose of 300 mg/kg/day.At the end of the experiment, the rats were anaesthetized and their adrenals were extracted and processed for light microscopic examination, immunohistochemical studies and quantitative image analysis.Results: Exposure of adult male rats to recurrent episodes of acute restraint stress resulted in diffuse vacuolar degeneration within the three zones of suprarenal cortex, with distortion of cellular cords, widened intercellular spaces and localized hemorrhage in suprarenal medulla. Acute restraint stress also caused statistically highly significant increase in the distribution of iNOS in both cortex and medulla within nerve cells and nerve fibers compared to the control group.On the other hand, concomitant treatment with L-arginine caused an apparent improved cellular architecture with marked decrease in the extent of vacuolar degeneration within all the three zones of suprarenal cortex, but areas of hyperemia within the cortex and congested blood capillaries in the medulla could be observed. Moreover, treatment with L-arginine resulted in statistically highly significant decrease in the distribution of iNOS within suprarenal gland with shift of activity of iNOS from suprarenal medulla to suprarenal cortex compared to the stress group. Still, there were, statistically, highly significant increase in the distribution of iNOS in suprarenal cortex within nerve cells and nerve fibers compared to the control group.Conclusion: The present study revealed that recurrent episodes of acute restraint stress caused microscopic degenerative changes in the suprarenal glands of adult male albino rats with decreased NOS activity within the suprarenal medulla. L-arginine improved such degenerative changes with increased NOS activity within the suprarenal medulla. However, a further study will be planned to correlate the dose and duration of L-arginine administration on the quality of such improvement.

The effect of high-fat diet on the structure of the colon and the possible protective role of L-arginine

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PP134. l-Arginine supplementation induces the expression of genes related to antioxidant defense in cultures of human vascular endothelial cells: Protective role for preeclampsia

IntroductionRecently, it has been proposed that supplementation with l-Arginine reduces the incidence of preeclampsia in high risk women, but the molecular mechanisms involved in the protective effect need to be determined. In addition, a critical role of l-Arginine in endothelial cell survival during oxidative stress, and the participation of neutrophils in the induction of oxidative stress during preeclampsia have been suggested. ObjectivesTo address if supplementation with l-arginine provides antioxidant defense in human vascular endothelial cells. MethodsHuman vascular endothelial cells (HUVECs) were isolated from umbilical cord veins obtained from healthy women underwent cesarean sections at term, with no evidence of hypertension disorders through the pregnancy. HUVECs were cultured in EndoGro media with LS supplement kit and 1% antibiotic with (n=10) or without 200uM l-Arginine (n=10). Confluent HUVECs were stimulated with neutrophils activated with 50umol/L arachidonic acid (1:16 ratio of neutrophil/cells). After incubation, cells were rinsed in PBS and harvested for RNA and protein extraction. Reverse transcription was performed using the RT2 First Strand kit, and expression gene profiling was generated using the RT2 Profiler PCR Array Human Oxidative Stress and Antioxidant Defense that includes the expression profile of 84 genes related to the oxidative pathway. Expression results were analyzed with the RT2 Profiler PCR Array Data Analysis Template v3.0 and two different lists of fold change in gene expression were generated: (1) HUVEC+neutrophils vs HUVEC+l-Arginine + neutrophils and (2) HUVEC vs HUVEC+neutrophils. Validation of the expression assays was performed using western blots or ELISAS for proteins expressed by selected genes. ResultsFold up- or down gene regulation are shown in Table 1. Forty six genes involved in oxidative stress defense were significantly up-regulated in HUVECs supplemented with l-arginine when were exposed to neutrophils. Interestingly, almost the same genes were down-regulated in non-supplemented HUVECs after neutrophil exposure. ▪ ConclusionSupplementation with l-Arginine upregulates the expression of genes related to antioxidant defense in primary cultures of endothelial cells. This finding provides a novel insight about the molecular mechanisms involved in the protective role of l-Arginine during preeclampsia.

Protective Role of l-Arginine Against Free-Radical Mediated Oxidative Damage in Patients with Unstable Angina.

Unstable angina is a critical condition of heart resulting from narrowing of vessels supplying blood to heart. Ischemia of the myocardium leads to oxidative stress and severe tissue damage. The objective of the present study was to determine the effect of l-arginine administration on the oxidant-antioxidant homeostasis which otherwise gets imbalanced in patients with cardiovascular diseases. The results obtained, show improvement in the oxidant-antioxidant levels of the subjects upon incorporation of l-arginine. Our findings suggest that supplementation of l-arginine along with regular anti-anginal therapy may be beneficial to the patients of unstable angina.

Blood ammonia elevation and toxicity from intravenous L-amino acid administration to dogs: the protective role of L-arginine.

A nontoxic intravenous l-amino acid mixture became markedly toxic when l-arginine and l-histidine were deleted from the mixture and was capable of producing convulsions and death in dogs. Associated with these infusions was a marked increase in blood ammonia levels that coincided with the signs of toxicity. Similar toxicity was produced by infusion of ammonium salts. Administration of l-arginine·HCl prior to or with the infused amino acid mixture prevented the toxicity and the blood ammonia rise. Subsequent injection of l-arginine·HCl produced a prompt fall in blood ammonia to normal levels. l-Ornithine·HCl or l-citrulline·HCl were similarly effective. d-Arginine·HCl and l-histidine·HCl were ineffectual. Urea production was more rapid when l-arginine was added to the infused amino acid mixture. The results suggest that the Krebs-Henseleit cycle is a functioning metabolic pathway that normally is a major deterrent to the accumulation of excessive blood ammonia when large amounts of amino acids are infused.