Biomedical subjects

Yukiko Minamiyama

Publications and source records attributed to Yukiko Minamiyama.

At least 19 recordsLinked to original sources

PubMed2007

Nicorandil elevates tissue cGMP levels in a nitric-oxide-independent manner.

The K(+) channel opener nicorandil is a hybrid compound that contains nitrate in its structure. It has been reported that nicorandil can relax vascular tissue in vitro via a mechanism that involves activation of K(ATP) channels and stimulation of soluble guanylyl cyclase. However, it is not known whether the increase of cGMP levels occurs through an elevation of nitric oxide (NO). The aim of the present study was to determine whether NO release was a direct effect of nicorandil. We reported here that nicorandil did not generate NO using ozone chemiluminescence detection methods in human or rat liver microsomes (P450-rich fractions) with addition of NADPH. However, nicorandil elevated cGMP levels in rat liver, aorta, and human coronary smooth muscle cells in vitro. The elevation was not inhibited by the NO trapping agent carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO). These results suggest that nicorandil elevates cGMP without NO generation.

Animals↗

PubMed2006

Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats.

Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. We determined the effects of calorie restriction (CR) on the dynamic aspects of mitochondrial ROS production, UCP2, and the nitric oxide (NO)-cGMP pathway in the cardiovascular tissues of type II diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Some rats were on restricted diets (30% reduction from free intake) from age 29 to 42 weeks. Blood glucose, hemoglobin A1c, plasma levels of free fatty acid, triacylglycerol, and plasminogen activator inhibitor-1 in OLETF rats were significantly higher than those in nondiabetic control [Long-Evans Tokushima Otsuka (LETO)] rats at 29 weeks. Mitochondrial ROS production and UCP2 expression significantly increased in the heart and aorta of OLETF rats compared with those in LETO rats. A fibrogenic growth factor, transforming growth factor (TGF)-beta1 in the coronary vessels, endothelial nitric-oxide synthase, and aortic nitrotyrosine were increased in OLETF rats at 42 weeks. In contrast, an index of the NO-cGMP pathway, phosphorylated vasodilator-stimulated phosphoprotein, and superoxide dismutase activity in the aorta were significantly diminished. The relationship between UCP2 and ROS production in the cardiovascular function of diabetic rats being fed a calorie-restricted diet is unknown. These abnormalities in OLETF rats were reversed to normal levels by CR. CR significantly improved the NO-cGMP pathway via normalizing ROS generation in OLETF rats. A decrease in UCP2 expression by CR may be a compensatory mechanism to counteract decreased intracellular oxidative stress. The data suggest that CR may prevent cardiovascular tissues from oxidative stress provoked by diabetes mellitus.

Animals↗

PubMed2006

Recovery of hepatic function determined by cytochrome P450-dependent drug metabolism lags after compensatory hepatic volume changes after portal vein ligation in rats.

BACKGROUND: Clinically, portal vein embolization has been proven to be useful as a preoperative treatment for major hepatic surgeries with impaired liver function. However, its effects on the metabolism and elimination of various drugs after portal vein embolization or ligation remain to be elucidated. MATERIALS AND METHODS: A portal vein branch that perfuses the central and left lobes of the liver of male Wistar rat was ligated, and changes in the weights of ligated and nonligated lobules as well as hepatic levels and activities of cytochrome P450 (CYP) isoforms, such as CYP3A2 and CYP2C11, were determined. To evaluate in vivo the effect of PVL on hepatic drug metabolism, the narcotic activity (sleep time) of midazolam, a specific substrate for CYP3A2, was measured. RESULTS: Although plasma levels of alanine aminotransferase and hepatic weight returned to basal levels at day 7 after the portal vein ligation, hepatic activities of CYP3A2 and CYP2C11 still remained low (53% and 54% of control levels, respectively), and returned to their initial levels after about day 14. The metabolism of midazolam was prolonged by approximately three times at day 7 after ligation and returned to basal levels at day 14. CONCLUSIONS: Because hepatic CYP-dependent drug metabolism by CYP isoforms recovered more slowly than the apparent recovery of hepatic volume and plasma alanine aminotransferase levels, the therapeutics of drugs metabolized by the CYP isoforms should be used carefully in patients who receive major hepatectomy with portal vein branch embolization.

Alanine Transaminase↗

PubMed2006

S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats.

This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.

Animals↗

PubMed2005

Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress.

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence). The peak of lipid peroxidation and free radical generation in the heart was reached before tolerance developed. In contrast, vitamin E-deficient hearts had lower P450 expression and higher free radical generation than control hearts. To evaluate other vitamin E-inhibitable mechanisms of nitrate tolerance, we studied the NO-cGMP pathway. NTG markedly reduced the vasodilator-stimulated phosphoprotein (VASP) serine 239 phosphorylation (specific substrate of cGMP-activated protein kinase I; cGK-I) in tolerant hearts. Vitamin E inhibited the depletion of pVASP. In conclusion, because continuous NTG infusion causes vitamin E depletion as well as nitrate tolerance, vitamin E deficiency may further accelerate nitrate tolerance via an increase in oxidative stress, the reduced bioconversion because of decreased P450 expression, and impairment of the NO/cGMP pathway in tolerant heart tissues.

Animals↗

PubMed2005

Minoxidil, a K(ATP) channel opener, accelerates DNA synthesis following partial hepatectomy in rats.

A large number of studies have reported the action of K(ATP) channel openers in accelerating the proliferation of hepatocytes and many other cell types in vitro. Few studies, however, have examined the proliferative effect of K(ATP) channel openers in vivo. The aim of this study was to determine whether the K(ATP) channel opener minoxidil accelerates liver regeneration after partial hepatectomy (PH) in vivo. Male Wistar rats underwent a 70% partial hepatectomy (PH) after receiving a subcutaneous injection of minoxidil (0.01 mg/kg or 0.03 mg/kg). Some of the rats were intravenously treated with 5-hydroxydecanoic acid (5-HD, 10 mg/kg) just before the minoxidil injection. Seventy-two hours after PH, DNA synthesis was immunohistochemically assessed by bromodeoxyuridine (BrdU) incorporation into the nuclei. Minoxidil induced significant and dose-dependent increase in the BrdU labeling index after PH, and 5-HD reversed this minoxidil-induced change. Minoxidil did not significantly affect the changes in liver weight and liver function after PH. The hepatic levels of prealbumin decreased by about 60% after PH and minoxidil inhibited the decrease. In conclusion, the K(ATP) channel opener minoxidil enhanced DNA synthesis after PH without affecting the liver function.

Alanine Transaminase↗

PubMed2004

FK778 and FK506 combination therapy to control acute rejection after rat liver allotransplantation.

BACKGROUND: In organ transplantation, several immunosuppressants are currently used to control graft rejection. Clinically, no single immunosuppressive agent can completely prevent posttransplantation immunoreaction; thus, combination therapy is usually performed. Novel agents with more powerful immunosuppressive activity and less toxicity need to be developed. METHODS: Lewis rat livers were orthotopically transplanted into Brown-Norway recipients. FK778 was administered orally from day 0 to day 6 to prevent acute rejection and from day 7 to day 13 to rescue ongoing rejection. To assess the combined effects, recipients were treated with intramuscular injection of FK506 and oral administration of FK778 from day 0 to day 6. Blood chemistry and histopathologic findings were measured to determine the patient's general condition and the graft condition. Allospecific antibodies were measured using enzyme-linked immunosorbent assays. The FK778 trough concentration was examined by using high-performance liquid chromatography. RESULTS: The acute immune response was suppressed by FK778 alone in a dose-dependent manner. The optimal FK778 dosage was determined to be 20 mg/kg per day, because adverse effects (weight loss and intestinal bleeding) occurred at 30 mg/kg per day. FK778 treatment from day 7 to day 13 rescued liver grafts from ongoing rejection. The intramuscular FK506 (0.125 mg/kg per day) injection and the oral FK778 (20 mg/kg per day) gavages suppressed acute liver graft rejection effectively and maintained better graft condition compared with monotherapy. CONCLUSIONS.: FK778 treatment effectively prevented acute rejection and rescued ongoing rejection after liver transplantation. The optimal dosage was determined to be 20 mg/kg per day. Combination therapy with FK506 was more beneficial than FK778 monotherapy.

Acute Disease↗

PubMed2004

CYP3A induction aggravates endotoxemic liver injury via reactive oxygen species in male rats.

We carried out this experiment to evaluate the relationship between isoforms of cytochrome P450 (P450) and liver injury in lipopolysaccharide (LPS)-induced endotoxemic rats. Male rats were intraperitoneally administered phenobarbital (PB), a P450 inducer, for 3 days, and 1 day later, they were intravenously given LPS. PB significantly increased P450 levels (200% of control levels) and the activities (300-400% of control) of the specific isoforms (CYP), CYP3A2 and CYP2B1, in male rats. Plasma AST and ALT increased slightly more in PB-treated rats than in PB-nontreated (control) rats with LPS treatment. Furthermore, either troleandomycin or ketoconazole, specific CYP3A inhibitors, significantly inhibited LPS-induced liver injury in control and PB-treated male rats. To evaluate the oxidative stress in LPS-treated rats, in situ superoxide radical detection using dihydroethidium (DHE), hydroxy-2-nonenal (HNE)-modified proteins in liver microsomes and 8-hydroxydeoxyguanosine (8-OHdG) in liver nuclei were measured in control and PB-treated rats. DHE signal intensity, levels of HNE-modified proteins, and 8-OHdG increased significantly in PB-treated rats. LPS further increased DHE intensity, HNE-modified proteins, and 8-OHdG levels in normal and PB-treated groups. CYP3A inhibitors also inhibited the increases in these items. Our results indicate that the induction or preservation of CYP isoforms further promotes LPS-induced liver injury through mechanisms related to oxidative stress. In particular, CYP3A2 of P450 isoforms made an important contribution to this LPS-induced liver injury.

Animals↗

PubMed2004

Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation.

We investigated the biological effects of the active oxygen produced by P450s. First, we identified which isoforms of P450 efficiently produced active oxygen using electron spin resonance. Eight forms of P450 purified from rat liver were used. Of these, CYP1A2, 2B1, 2C11 and 3A2 produced hydroxyl radicals efficiently. Phenobarbital (PB) which is a typical inducer of CYP2B1 and 3A2 induced production of hydroxyl radicals by rat liver and ketoconazole, an inhibitor of P450, inhibited production of hydroxyl radicals in vitro. PB is a tumor promoter as well as the P450-inducer. We investigated oxidation of the genomic DNA by the hydroxyl radicals produced by PB-inducible P450 in vitro and in vivo. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation in vivo was assayed by HPLC. PB strongly induced the production of 8-OHdG in the rat liver. While ketoconazole inhibited the production of 8-OHdG in vivo. These results suggest that active oxygen produced by P450 oxidized genomic DNA and induction of P450 increased oxidative stress that may contribute to tumor initiation and promotion.

Animals↗

PubMed2004

A fermented grain food mixture, AOB, inhibits liver metastasis in the metastasis model of rat colon cancer.

Natural antioxidants have been shown to be rich sources of microchemicals with the potential to prevent human cancers. We examined whether dietary supplement of a fermented grain food mixture (AOB), which has been shown to have a strong antioxidative effect, may protect against colon cancer metastasis. At day 5 of AOB (6.5%) supplementation in a basal diet, the rat colon cancer cells (RCN-H4) were injected beneath the capsule of the spleen and one min later rats were splenectomized. All rats without AOB supplementation had multiple liver metastases. However, the number and the size of liver tumors were reduced by about 80% in AOB group. Combined use of cisplatin and AOB enhanced an anti-metastatic effect. The inhibition of liver metastasis by AOB was caused by the regulation of cell cycle. This product may be used as an adjuvant in the therapy of malignant neoplasia.

Animals↗

PubMed2004

Continuous treatment with organic nitrate affects hepatic cytochrome P450.

We previously reported that cytochrome P450 (P450) is a key enzyme of organic nitrate biotransformation and that P450 levels of the heart and its vessels markedly decreased at the development of nitrate tolerance. Escape from tolerance of organic nitrate by induction of cytochrome P450. Most organic nitrates, including nitroglycerin (NTG), are metabolized in the liver, where nitric oxide (NO) is concomitantly produced from the organic nitrates. Therefore, organic nitrate administration may also affect hepatic P450 levels, since the liver is the major organ of P450-related metabolism. Male Wistar rats were intravenously administrated NTG or isosorbide dinitrate (ISDN) for 24-96 h. Hepatic P450 was drastically decreased after 48 h or 72 h of continuous NTG or ISDN infusion, when nitrate tolerance was observed, but it recovered 48 h after cessation of the drug administration. hemeoxygenase-1 (HO-1) was induced within 24 h of continuous NTG infusion, but it returned to normal levels 48 h after cessation of the NTG. The administration of sodium nitroprusside, an agent to which the animals showed no tolerance, did not induce HO-1 or P450 depletion as judged by SDS-PAGE in combination with Western-blotting. These results suggest that P450-dependent drug metabolism may be drastically affected after continuous organic nitrate administration.

Animals↗

PubMed2003

Continuous administration of organic nitrate decreases hepatic cytochrome P450.

We previously reported that cytochrome P450 (P450) is a key enzyme of organic nitrate biotransformation and that P450 levels of the heart and its vessels markedly decreased at the development of nitrate tolerance. Although our attention was mainly focused on the circulatory organs, most organic nitrates, including nitroglycerin (NTG), are metabolized in the liver, where nitric oxide (NO) is concomitantly produced from the organic nitrates. NO reacts with various molecules such as superoxide, heme, thiols, and oxygen. This paper examined whether hepatic P450 levels are also affected after organic nitrate administration, since the liver is the major organ of P450 related metabolism. Male Wistar rats were intravenously administrated NTG or isosorbide dinitrate (ISDN) for 24-96 h. We observed the level of hemeoxygenase-1 (HO-1) as the functional marker of hepatic P450, since one of the acute phase target proteins of NO induction is an inducible type of HO-1. Hepatic P450 was drastically decreased after 48 or 72 h of continuous NTG or ISDN infusion, when nitrate tolerance was observed, but it recovered 48 h after cessation of the NTG administration. HO-1 was induced within 24 h of continuous NTG infusion, but it returned to normal levels 48 h after cessation of NTG. The administration of sodium nitroprusside, an agent to which the animals showed no tolerance, did not induce HO-1 or P450 depletion. Chronic administration of organic nitrates significantly decreased hepatic P450. These results suggest that P450-dependent drug metabolism may be drastically affected after continuous organic nitrate administration.

Animals↗

PubMed2003

Saccharated colloidal iron enhances lipopolysaccharide-induced nitric oxide production in vivo.

We investigated the effects of iron on the production of nitric oxide (NO), inducible NO synthase (iNOS), and plasma cytokines induced by lipopolysaccharide (LPS) in vivo. Male Wistar rats were preloaded with a single intravenous injection of saccharated colloidal iron (Fesin, 70 mg iron/kg body weight) or normal saline as a control, and then given an intraperitoneal injection of LPS (5.0 mg/kg body weight). Rats, preloaded with iron, had evidence of both iron deposition and strong iNOS induction in liver Kupffer cells upon injection of LPS; phagocytic cells in the spleen and lung had similar findings. LPS-induced NO production in iron-preloaded rats was significantly higher than control rats as accessed by NO-hemoglobin levels measured by ESR (electron spin resonance) and NOx (nitrate plus nitrite) levels. Western blot analysis showed that iron preloading significantly enhanced LPS-induced iNOS induction in the liver, but not in the spleen or lung. LPS-induced plasma levels of IL-6, IL-1beta, and TNF-alpha were also significantly higher in iron-preloaded rats as shown by ELISA, but IFN-gamma levels were unchanged. We conclude that colloidal-iron phagocytosed by liver Kupffer cells enhanced LPS-induced NO production in vivo, iNOS induction in the liver, and release of IL-6, IL-1beta, and TNF-alpha.

Animals↗

PubMed2003

Fermented grain products, production, properties and benefits to health.

Fermented foods such as Japanese traditional food "miso (fermented soy bean paste)" have been shown to be rich source of micronutrients with the potential to prevent various human diseases. We have introduced effects of a new dietary supplement of fermented grain foods mixture containing extracts from wheat germ, soybeans, rice bran, tear grass, sesame, wheat, citrus lemon, green tea, green leaf extract and malted rice under the trade name of antioxidant biofactor (AOB). Chemical analysis of AOB shows the presence of various phenolic compounds (catechins, rutin, genistin, daidzin, etc.). AOB has strong antioxidant properties and additional biological effects, which might be of importance in context with the prevention of degenerative diseases. This paper focuses on the effect of supplementing AOB in various animal models and humans.

Journal Article↗

PubMed2003

Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat.

Dietary nitrate is reduced to nitrite by some oral bacteria and the resulting nitrite is converted to nitric oxide (NO) in acidic gastric juice. The aim of this study is to elucidate the pathophysiological role of dietary nitrate in the stomach. Intragastric administration of nitrate rapidly increased nitrate and NO in plasma and the gastric headspace, respectively. Water-immersion-restraint stress (WIRS) increased myeloperoxidase (MPO) activity in gastric mucosa and induced hemorrhagic erosions by a nitrate-inhibitable mechanism. In animals that had received either cardiac ligation or oral treatment with povidone-iodine, a potent bactericidal agent, administration of nitrate failed to increase gastric levels of NO and to inhibit WIRS-induced mucosal injury. WIRS decreased gastric mucosal blood flow by a mechanism which was inhibited by administration of nitrate. These data suggested that the enterosalivary cycle of nitrate and related metabolites consisted of gastrointestinal absorption and salivary secretion of nitrate, its conversion to nitrite by oral bacteria and then to NO in the stomach might play important roles in the protection of gastric mucosa from hazardous stress.

Animals↗

PubMed2003

Targeting superoxide dismutase to renal proximal tubule cells attenuates vancomycin-induced nephrotoxicity in rats.

Vancomycin hydrochloride (VCM), a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). As it is known to induce renal dysfunction, the dose and the duration of its administration are limited. Moreover, the mechanism of VCM-induced renal dysfunction remains to be unclear. To evaluate the involvement of free radical on VCM-induced renal dysfunction, we carried out analysis with a hexamethylenediamine-conjugated superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Male Wistar rats (weighing 200-210 g) were intraperitonealy administered with 200 mg/kg of VCM twice a day for 7 days. AH-SOD 5 mg/kg/day was subcutaneously injected 5 min before every VCM injection. VCM induced renal injury dose-dependently. Biochemical analyses revealed that plasma levels of blood urea nitrogen and creatinine significantly increased in the VCM-treated group by an AH-SOD-inhibitable mechanism. VCM simultaneously elicited an increase of 8-OHdG levels and chemiluminescence intensity of free radical generation in the kidney. Histological examination revealed that VCM also elicited a marked destruction of glomeruli and necrosis of proximal tubules. AH-SOD inhibited these phenomena in the kidney. These results suggested that oxidative stress might underlie the pathogenesis of VCM-induced nephrotoxicity and targeting SOD and/or related antioxidants to renal proximal tubules might permit the administration of higher doses of VCM sufficient for eradication of MRSA without causing renal injury.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Mediation of arachidonic acid metabolite(s) produced by endothelial cytochrome P-450 3A4 in monkey arterial relaxation.

We investigated mechanisms of endothelium-dependent relaxation by acetylcholine resistant to indomethacin and N(G)-nitro-L-arginine and sensitive to cytochrome P-450 (CYP) inhibitors or charybdotoxin + apamin in the monkey lingual artery. Treatment with quinacrine, an inhibitor of phospholipase A2, abolished the relaxation by acetylcholine. However, treatment with alpha-glycyrrhetinic acid, an inhibitor of gap junctions, or catalase, an enzyme which dismutates hydrogen peroxide to form water and oxygen, did not affect the relaxation by acetylcholine. Immunohistochemistry demonstrated the presence of CYP3A4 in endothelial cells of the artery. Anti-CYP3A4 antibody inhibited relaxations by products of arachidonic acid incubated with human liver microsomes rich in CYPs in the endothelium-denuded artery. Purified CYP3A4 produced epoxyeicosatrienoic acids (EETs) from arachidonic acid, and the production was abolished by a selective CYP3A inhibitor, ketoconazole. It may be concluded that endothelium-derived relaxing substance(s) other than nitric oxide and prostanoids in the monkey lingual artery opens charybdotoxin + apamin-sensitive K+ channels in smooth muscle cells, and arachidonic acid metabolite(s) produced by endothelial CYP3A4 is likely to be the major substance.

Acetylcholine↗

PubMed2002

Down-regulation of spontaneous Epstein-Barr virus reactivation in the P3HR-1 cell line by L-arginine.

We tested the hypothesis that inhibition of Epstein-Barr virus (EBV) reactivation is controlled in part by nitric oxide (NO) generated from L-arginine (Arg). The spontaneous reactivation of EBV in the Burkitt's lymphoma (BL) cell line P3HR-1 was inhibited when the cells were cultured in L-Arg-supplemented medium. The expression of EBV early antigen (EA), immediate-early BZLF1 mRNA and the protein ZEBRA, and production of infectious virus were reduced by L-Arg supplementation in a dose-dependent manner. We demonstrated that inducible NO synthase (iNOS) mRNA was constitutively expressed in P3HR-1 cells, as quantitated by the reverse transcription-polymerase chain reaction. L-Arg supplementation enhanced iNOS and NOx expression in the cells. A specific NOS inhibitor, NG-monomethyl-L-Arg enhanced the expression of ZEBRA and early BMRF1 protein EA-D in the cells. L-Arg supplementation also inhibited the spontaneous EBV reactivation in another BL cell line EB1 and a B lymphoblastoid cell line OB. These results indicated that L-Arg induces iNOS and generates NO, which inhibits EBV reactivation in EBV-positive cells.

Arginine↗