Nodularin
Based on 1 Customer Validation
Nodularin is a hepatotoxin, tumor promoter, and protein phosphatase inhibitor. Nodularin induces apoptosis (apoptosis) in normal cells (including caspase activation, upregulation of Bcl‑XS, and upregulation of BAX/P53), triggers hyperphosphorylation of the MAPK/ERK, mTOR/S6K and p38 MAPK signaling pathways, and induces oxidative stress, endoplasmic reticulum membrane instability, peroxisome proliferation and increased lysosomal enzyme activity. Nodularin promotes DEN (HY-N7434)-initiated hepatocyte proliferation and adenoma formation, and inhibits proliferation, phagocytosis and chemotaxis of normal lymphocytes, oocyte maturation and vitellogenesis, as well as angiogenesis. Nodularin exhibits hepatotoxicity, reproductive and endocrine toxicity, and embryonic developmental toxicity in various animal models. Nodularin can be used in studies related to liver cancer, hepatotoxicity and reproductive endocrine toxicity.
For research use only. We do not sell to patients.
- Purity: 99.85%
- CAS No.: 118399-22-7
- Formula: C41H60N8O10
- Molecular Weight:824.96
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Storage:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Nodularin (1 mM) induces the expression of TNF-α, fos family proto-oncogenes and jun family proto-oncogenes in primary hepatocytes of male Fischer 344 rats[1].
Nodularin (2.5-10 μg/L; 6 h) inhibits human chorionic gonadotropin (HCG)-induced germinal vesicle breakdown (GVBD) in late vitellogenic oocytes of female zebrafish (Danio rerio), and reduces their maturation rates to 47.33%, 43.67% and 36.67%, respectively[3].
Nodularin (200 nM; 10 min) disrupts the colocalization of SOD1 and actin filaments in primary rat hepatocytes, which is characterized by the reorganization of actin into aggregates, while SOD1 remains in the submembrane region[4].
Nodularin (200 nM; 20 min) abolishes the weak interaction between SOD1 and actin in primary rat hepatocytes, as detected by co-immunoprecipitation and Western blotting[4].
Nodularin (5-200 nM; 2-20 min) induces apoptosis in primary rat hepatocytes, accompanied by membrane budding and actin rearrangement; specifically, 5 μM triggers the effect within 2-4 minutes, while 200 nM triggers the effect within 10-20 minutes[4].
Nodularin (5 μM; 2 min) alters the subcellular localization of SOD1 in primary rat hepatocytes, shifting it from the submembrane region to apoptotic membrane budding structures[4].
Nodularin (200 nM; 20 min) causes massive accumulation of SOD1 in the cytoplasmic matrix and endoplasmic reticulum lamellae of apoptotic bodies in primary rat hepatocytes, with only a small amount localized in mitochondria and endoplasmic reticulum[4].
Nodularin (200 nM; 10 min) induces phosphorylation of SOD1 in primary rat hepatocytes, generating two distinct phosphorylated isoforms (P1 and P2) detectable by autoradiography[4].
Nodularin (5 μM; 2 min) significantly increases the phosphorylation level of SOD1 in primary rat hepatocytes, and two distinct phosphorylated isoforms (P1 and P2) are detectable via immunoprecipitation and autoradiography[4].
Nodularin (5 μM; 1.5-4 min) induces ROS production in primary rat hepatocytes, with approximately 50% of cells showing positive ROS staining at 1.5 min and 4 min post-exposure[4].
Nodularin (200 nM; 10 min) does not alter the enzymatic activity of SOD1 in primary rat hepatocytes, and CaMKII inhibition has no effect on this activity[4].
Nodularin (200 nM; 10 min) induces CaMKII-dependent post-translational modifications (phosphorylation and/or oxidation) of SOD1 in primary rat hepatocytes, which can be detected as an acidic shift by two-dimensional Western blotting[4].
Nodularin (1-10 μg/mL; 6-48 h) induces dose- and time-dependent basal DNA strand breaks and oxidative DNA damage (oxidized purines) in HepG2 cells, with the peak of damage occurring at 24 h; significant micronucleus formation in HepG2 cells is induced only at a concentration of 2.5 μg/mL and for durations of 24 h or longer[6].
Nodularin (1-10 μg/mL; 6-48 h) induces apoptosis in HepG2 cells in a dose- and time-dependent manner[6].
Nodularin (0.1-200 nM; 24 h) induces concentration-dependent increases in the activities of caspase 8, 9, and 3/7, as well as concentration-dependent nuclear apoptosis, in primary rat hepatocytes[7].
Nodularin (100-200 nM; 24 h) induces DNA fragmentation in primary rat hepatocytes[7].
Nodularin (10-100 nM; 1-8 h) induces time- and concentration-dependent hyperphosphorylation of ERK1/2, p90RSK (Ser380), p90RSK (Thr359/Ser363), p85S6K (Thr412), p70S6K (Thr389) and p38 (Thr180/Tyr182) in primary rat hepatocytes[7].
Nodularin (5-10 μg/mL; 24 h) exhibits aneuploidy-inducing activity in HepG2 cells and induces the formation of centromere-positive micronuclei[6].
Nodularin (10-100 nM; 1-24 h) induces a time- and concentration-dependent increase in total Bcl-xL levels in primary rat hepatocytes, with significant late activation observed after 24 h[7].
Nodularin (1-10 µg·mL-1; 2 h) neither inhibits nor enhances the in vitro free radical scavenging (antioxidant) activity of purified glutathione (GSH)[8].
Nodularin (0.001-0.1 μg/mL; 24 h) induces concentration-dependent cytotoxicity in primary carp head kidney leukocytes and CLC cells, with primary head kidney leukocytes showing higher sensitivity: significant cytotoxicity appears at concentrations ≥0.05 μg/mL, whereas CLC cells exhibit a significant effect only at 0.1 μg/mL[9].
Nodularin (0.001-0.1 μg/mL; 2 h) increases ROS/RNS production in CLC cells and primary carp head kidney leukocytes at all tested concentrations, without showing a clear dose-dependent response[9].
Nodularin (0.001-0.01 μg/mL; 24 h) regulates the mRNA expression of cytokines in CLC cells and primary head kidney leukocytes of carp. It significantly increases TNF-α expression at both tested concentrations, but exerts no significant effect on TGF-β expression[9].
Nodularin (0.001-0.1 μg/mL; 24 h) induces dose-dependent inhibition of phagocytic activity in CLC cells and primary carp head kidney leukocytes, with significant inhibition observed at concentrations ≥0.01 μg/mL[9].
Nodularin (0.001-0.1 μg/mL; 24 h) exerts a dose-dependent inhibitory effect on the chemotaxis of primary carp head kidney leukocytes and CLC cells, and the inhibitory response of primary head kidney leukocytes is stronger at all effective concentrations[9].
At non-cytotoxic concentrations, Nodularin (0.001-0.05 μg/mL; 24 h) does not affect the production or release of IL-1β in LPS (HY-D1056A1)-stimulated CLC cells[9].
Nodularin (0.001-0.1 μg/mL; 72 h) significantly inhibits the proliferation of primary head kidney (HK) lymphocytes from common carp at concentrations ≥0.01 μg/mL, and the inhibitory effect is stronger when used in combination with concanavalin A (ConA) stimulation[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2 human hepatoma cells
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Concentration:1, 2.5, 5 and 10 μg/mL
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Incubation Time:6, 12, 24 and 48 h
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Result:Increased the frequency of apoptotic cells steadily with treatment time and dose, with significant elevations observed at 10 μg/mL for 12 and 24 h, and at 5 and 10 μg/mL for 48 h.\nIncreased the frequency of early apoptotic cells in a dose-dependent manner, peaking at 24 h, with significant elevations observed at 10 μg/mL for 6, 12, 24, and 2.5, 5, 10 μg/mL for 48 h.
Increased the frequency of late apoptotic + necrotic cells gradually with dose and treatment time, reaching a peak at 48 h, with significant elevations observed at 10 μg/mL for 12, 24, and 2.5, 5, 10 μg/mL for 48 h.
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Cell Line:Primary rat hepatocytes
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Concentration:0.1, 1, 10, 50, 100 and 200 nM
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Incubation Time:24 h
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Result:Induced a concentration‑dependent increase in the activities of caspase 8, caspase 9, and caspase 3/7 in primary rat hepatocytes after 24 h of exposure.
Caspase 9 and caspase 3/7 were significantly activated at concentrations of 50 nM and above, whereas caspase 8 showed a significant increase only at 100 nM.
Consistent with the activation of caspases, it also induced nuclear apoptosis, as evidenced by condensed, fragmented, or crescent‑shaped nuclei in DAPI‑stained cells at concentrations of 50 nM and above.
DNA fragmentation was observed at 100 and 200 nM.
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Cell Line:Primary rat hepatocytes
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Concentration:10, 50 and 100 nM
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Incubation Time:1, 2, 3, 4, 6, 7 and 8 h
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Result:Induced a time- and concentration-dependent increase in ERK1/2 phosphorylation in primary rat hepatocytes. Significant activation was observed from 6 h onward at 100 nM, from 7 h onward at 50 nM, and from 8 h onward at 10 nM.
Induced a time- and concentration-dependent increase in p90RSK (Ser380) phosphorylation. Significant activation was observed at 10 nM from 3 h onward, with maximal increases of approximately 5- to 6-fold at later time points.
Induced a time- and concentration-dependent increase in p90RSK (Thr359/Ser363) phosphorylation. Significant activation was observed at 10 nM from 6 h onward, with maximal increases of up to 7-fold at 8 h.
Induced a time- and concentration-dependent increase in p85S6K (Thr412) and p70S6K (Thr389) phosphorylation. Significant activation in the higher concentration groups was observed from 6 h onward, with maximal increases of up to 12-fold for p85S6K phosphorylation at later time points.
Induced a time- and concentration-dependent increase in p38 (Thr180/Tyr182) phosphorylation. Significant activation at 50 nM was observed from 2 h onward, whereas significant activation at all tested concentrations (≥10 nM) was observed from 4 h onward.
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Cell Line:carp leucocyte cell line (CLC) cells, primary common carp (Cyprinus carpio L.) head kidney (HK) leukocytes
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Concentration:0.001, 0.01, 0.05 and 0.1 μg/mL
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Incubation Time:24 h
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Result:Reduced mitochondrial activity to 75% of control and membrane integrity to 76% of control in primary HK leukocytes at 0.05 μg/mL.
Reduced mitochondrial activity to 68% of control and membrane integrity to 45% of control in primary HK leukocytes at 0.1 μg/mL.
Reduced mitochondrial activity to 89% of control and membrane integrity to 82% of control in CLC cells at 0.1 μg/mL.
Caused no significant cytotoxicity at 0.001 or 0.01 μg/mL for either cell type.
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Cell Line:CLC cells, primary common carp HK leukocytes
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Concentration:0.001, 0.01, 0.05, 0.1 μg/mL
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Incubation Time:24 h
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Result:Reduced migration to ~52% of control in primary HK leukocytes at 0.01 μg/mL.
Reduced migration to ~33% of control in primary HK leukocytes at 0.05 μg/mL.
Reduced migration to ~30% of control in primary HK leukocytes at 0.1 μg/mL.
Reduced migration to ~80% of control in CLC cells at 0.01, 0.05, and 0.1 μg/mL.
Caused no significant reduction in migration for either cell type at 0.001 μg/mL.
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Cell Line:CLC cells, primary common carp HK leukocytes
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Concentration:0.001 and 0.01 μg/mL
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Incubation Time:24 h
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Result:Increased IL-1β mRNA expression by 2.5-fold relative to control in primary HK leukocytes at 0.01 μg/mL, with no effect on CLC cells.
Increased TNF-α mRNA expression by ~4-fold in CLC cells and ~2.5-fold in HK leukocytes at 0.001 μg/mL.
Increased TNF-α mRNA expression by ~3-fold in CLC cells and ~3.2-fold in HK leukocytes at 0.01 μg/mL, with no clear dose-dependency.
Increased IL-10 mRNA expression by 1.9-fold in CLC cells and 3.2-fold in HK leukocytes at 0.001 μg/mL, while 0.01 μg/mL had no significant effect.
Caused a slight, non-significant upregulation of TGF-β mRNA expression in both cell types at both concentrations.
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Cell Line:LPS-stimulated CLC cells
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Concentration:0.001, 0.01, 0.05 μg/mL
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Incubation Time:24 h
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Result:Caused no statistically significant changes in extracellular or intracellular IL-1β levels compared to control cells at any tested concentration.
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Cell Line:primary common carp HK leukocytes
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Concentration:0.001, 0.01, 0.05, 0.1 μg/mL
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Incubation Time:72 h
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Result:Reduced HK lymphocyte proliferation significantly compared to control at 0.01, 0.05, and 0.1 μg/mL.
Caused significantly lower proliferation levels in the Nodularin + ConA group (0.01 to 0.1 μg/mL Nodularin) than those with Nodularin alone.
Caused no significant reduction in proliferation at 0.001 μg/mL.
A single intraperitoneal administration of Nodularin (8 μg/kg) causes a statistically significant increase in the activities of hepatic β-D-glucuronidase, α-glucosidase, lysosomal esterase and N-acetylglucosaminidase in multiple cellular fractions within 24 h, with the peak effect typically occurring at 30 min post-administration, and also induces endoplasmic reticulum membrane instability[2].
Nodularin (2.5-10 μg/L; waterborne exposure; continuous exposure for 14 days) disrupts the reproductive endocrine system of female zebrafish by reducing the levels of gonadotropins and E2, increasing T levels, altering oocyte development, inducing oxidative stress, and regulating gene expression in the hypothalamic-pituitary-gonadal-liver axis[3].
Nodularin (0.5-4 μM; immersion; initiated at 3 hours post-fertilization until the end of the experiment) induces dose-dependent developmental toxicity, oxidative stress, and apoptosis in zebrafish embryos, with the most severe effects observed at the 4 μM dose[5].
Nodularin (25 μg/kg; i.p.; twice a week; for 10 consecutive weeks) induces selective atrophy of the left and caudal liver lobes in normal saline-pretreated F344 rats through sustained inhibition of PP1/PP2A, peroxisome proliferation, and induction of the pro-apoptotic protein Bcl-Xs, while promoting enlargement of the right and middle liver lobes via upregulation of the anti-apoptotic protein Bcl-Xl[10].
Nodularin (25 μg/kg; i.p.; twice a week; for 10 consecutive weeks) promotes hepatocyte proliferation and adenoma formation in DEN (HY-N7434)-induced F344 rats by restoring PP1/PP2A activity, promoting peroxisome proliferation, maintaining the expression of the anti-apoptotic protein Bcl-XL, and simultaneously blocking hepatic lobe atrophy[10].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:7-week-old male Fischer 344 rats (F344/KIST substrain) were given a single intraperitoneal injection of N-nitrosodiethylamine (DEN, 200 mg/kg body weight) at week 0, and subsequent administrations were started from week 3
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Dosage:25 µg/kg
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Administration:i.p.; twice weekly; 10 weeks
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Result:Increased area of eosinophilic nodules to 13.43 mm2/cm2 by week 12, up from 3.23 mm2/cm2 at week 10.
Peaked frequency of homogeneously stained GST-P-positive dense nodules (DN) at 124.5 nodules/cm2 by week 12, then decreased to 60.0 nodules/cm2 by week 18.
Detected heterogeneously stained GST-P-positive pale nodules (PN) first at week 15, reaching 18.0 nodules/cm2 by week 22.
Peaked total area of GST-P-positive nodules at 47.5 mm2/cm2 by week 12, then decreased to 31.5 mm2/cm2 by week 18, with PN areas reaching 7.8 mm2/cm2 by week 22.
Recorded PCNA labeling indices at week 12 of 43.9 nuclei/100 hepatocytes in background parenchyma and 34.3 nuclei/100 hepatocytes in DN, both significantly higher than control (8.5).
Observed background PCNA indices dropped to 11.4 nuclei/100 hepatocytes by week 15, while DN retained a significantly higher index of 30.5; PN had an index of 18.0, higher than control but lower than DN.
Measured PN PCNA index of 12.2 nuclei/100 hepatocytes and DN PCNA index of 32.6 nuclei/100 hepatocytes by week 22.
Peaked PCNA indices in nodularin-only group at 38.4 nuclei/100 hepatocytes at week 12, then returned to control levels (10.2) by week 22.
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Animal Model:Swiss mice (8-week-old female, 22-25 g)[2]
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Dosage:8 μg/kg
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Administration:i.p.; single injection
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Result:Increased β-D-glucuronidase activity to 157% at 15 min, 175% at 30 min, 130% at 60 min, and 150% at 24 h in complete liver homogenate.
Increased α-glucosidase activity to 150% at 15 min, 162% at 30 min, 133% at 60 min, and 148% at 24 h in complete liver homogenate.
Increased lysosomal esterase activity to 130% at 30 min and 153% at 24 h in complete liver homogenate.
Increased N-acetyl-glucosaminidase activity to 162% at 30 min and 143% at 60 min in complete liver homogenate.
Increased β-D-glucuronidase activity to 220%, 242%, 213%, and 248% in lysosomal fraction at 15, 30, 60 min, and 24 h; increased to 204%, 173%, 150%, and 146% in microsomal fraction at 15, 30, 60 min, and 24 h; decreased to 51%, 70%, 38%, and 63% in cytosol fraction at 15, 30, 60 min, and 24 h.
Increased α-glucosidase activity to 162%, 175%, 153%, and 171% in lysosomal fraction at 15, 30, 60 min, and 24 h; increased to 159% at 15 min and 167% at 30 min in cytosol fraction; decreased to 45%, 54%, 36%, and 63% in microsomal fraction at 15, 30, 60 min, and 24 h.
Increased lysosomal esterase activity to 178% at 60 min and 171% at 24 h in lysosomal fraction; decreased to 66% at 60 min in microsomal fraction.
Increased N-acetyl-glucosaminidase activity to 157%, 177%, and 164% in lysosomal fraction at 15, 30, and 60 min; increased to 190% at 30 min and 143% at 24 h in cytosol fraction; decreased to 51%, 59%, 44%, and 69% in microsomal fraction at 15, 30, 60 min, and 24 h.
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Animal Model:Danio rerio (adult female)[3]
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Dosage:2.5 μg/L; 5 μg/L; 10 μg/L
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Administration:waterborne exposure; continuous; 14 days
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Result:Decreased gonadosomatic index (GSI) by 4.75% (to 14.68%), 8.83% (to 10.60%), and 11.04% (to 8.39%) in the 2.5 μg/L, 5 μg/L, and 10 μg/L groups, respectively, compared to control (19.43%).
Decreased hepatosomatic index (HSI) by 0.6% (to 1.82%), 0.89% (to 1.53%), and 1.11% (to 1.31%) in the 2.5 μg/L, 5 μg/L, and 10 μg/L groups, respectively, compared to control (2.42%).
Increased perinucleolus stage oocytes to 24%, 33%, and 40%; cortical alveolus stage oocytes to 25%, 28%, and 30%; decreased vitellogenic stage oocytes to 27%, 24%, and 21%; post-vitellogenic stage oocytes to 24%, 15%, and 9% in the 2.5 μg/L, 5 μg/L, and 10 μg/L groups, respectively, compared to control values of 20%, 22%, 30%, and 28%.
Decreased follicle-stimulating hormone (FSH) levels to 25.93 mIU/mL (2.5 μg/L), 19.57 mIU/mL (5 μg/L), and 16.08 mIU/mL (10 μg/L) compared to control (28.16 mIU/mL), with significant decreases at 5 μg/L and 10 μg/L.
Decreased luteinizing hormone (LH) levels to 8.20 mIU/mL (2.5 μg/L), 5.11 mIU/mL (5 μg/L), and 4.48 mIU/mL (10 μg/L) compared to control (14.27 mIU/mL), with significant decreases at all doses.
Decreased 17β-estradiol (E2) levels to 26.67 pg/mL (2.5 μg/L), 20.25 pg/mL (5 μg/L), and 16.95 pg/mL (10 μg/L) compared to control (39.33 pg/mL), with significant decreases at 5 μg/L and 10 μg/L.
Increased testosterone (T) levels to 109.71 pg/mL (2.5 μg/L), 121.65 pg/mL (5 μg/L), and 127.74 pg/mL (10 μg/L) compared to control (100.48 pg/mL), with significant increases at 5 μg/L and 10 μg/L.
Decreased E2/T ratio significantly at all nodularin doses.
Increased ovarian malondialdehyde (MDA) content to 0.0138 μM/mg (2.5 μg/L), 0.0139 μM/mg (5 μg/L), and 0.0141 μM/mg (10 μg/L) compared to control (0.0123 μM/mg).
Increased ovarian DPPH radical scavenging activity to 81.76% (2.5 μg/L), 83.01% (5 μg/L), and 83.96% (10 μg/L) compared to control (75.76%).
Upregulated oxidative stress genes (sod, cat, gpx) in the brain, ovary, and liver at all nodularin doses; at 10 μg/L, sod was upregulated 1.75-fold (ovary), 3.45-fold (liver), 2.73-fold (brain); cat was upregulated 2.11-fold (ovary), 3.40-fold (liver), 1.63-fold (brain); gpx was upregulated 1.77-fold (ovary), 1.45-fold (liver), 2.44-fold (brain).
Upregulated brain genes gnrh2 and gnrh3 1.69/2.39-fold and 1.68/2.61-fold at 5/10 μg/L, respectively; upregulated cyp19a1b 1.81-fold at 10 μg/L; downregulated fshβ 0.57/0.54-fold at 5/10 μg/L; downregulated lhβ 0.73/0.47/0.473-fold at 2.5/5/10 μg/L.
Downregulated ovary genes fshr, 3βhsd, and cdc2 at all doses; downregulated lhr 0.62/0.59-fold at 5/10 μg/L; downregulated 20βhsd 0.41/0.3-fold at 5/10 μg/L; downregulated cyp19a1a 0.52/0.11-fold at 5/10 μg/L; downregulated nprα, mprα, 17βhsd, and cyclinβ at 5/10 μg/L.
Downregulated liver genes vtg1 0.73/0.28-fold at 5/10 μg/L; downregulated vtg2 0.74-fold at 10 μg/L; downregulated vtg3 0.71/0.47/0.23-fold at 2.5/5/10 μg/L.
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Animal Model:Zebrafish (Danio rerio) embryos of wild-type AB strain, Tg(flk1:EGFP) transgenic line, and Tg(fli1a:NGFP) transgenic line were used. Exposure was initiated at 3 hours post fertilization (hpf)[5]
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Dosage:0.5 μM, 1 μM, 2 μM, 4 μM
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Administration:immersion; continuous; from 3 hpf through experimental endpoint
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Result:Decreased hatching rates to 73.84% (2 μM) and 70.00% (4 μM) at 48 hpf.
Increased mortality rates to 25.00% (0.5 μM), 36.65% (1 μM), 42.50% (2 μM), and 53.00% (4 μM) at 96 hpf.
Increased heart rates to 104.00 bpm (1 μM), 104.50 bpm (2 μM), 110.00 bpm (4 μM) at 48 hpf, and decreased heart rates to 81.00 bpm (2 μM) and 80.00 bpm (4 μM) at 96 hpf.
Increased malformation rates to 43.75% (2 μM) and 67.50% (4 μM) at 96 hpf.
Increased uninflated swim bladder rates to 1.14-fold (0.5 μM), 1.28-fold (1 μM), 1.51-fold (2 μM), and 1.83-fold (4 μM) of control at 96 hpf.
Increased pericardium areas to 0.25 mm2 (2 μM) and 0.29 mm2 (4 μM) at 96 hpf.
Increased sinus venosus-bulbus arteriosus distances to 0.43 mm (2 μM) and 0.47 mm (4 μM) at 96 hpf.
Decreased body lengths to 2.76 mm (2 μM) and 2.83 mm (4 μM) at 96 hpf.
Decreased eye area to 0.04 mm2 (4 μM) at 96 hpf.
Decreased axon length to 81.65 μm (4 μM) at 96 hpf.
Reduced caudal fin length and width to 73.85% and 75.63% of control, respectively (4 μM) at 96 hpf.
Decreased dorsal aorta width to 19.33 × 103 mm (2 μM) and 18.75 × 103 mm (4 μM) at 72 hpf.
Increased DA-DLAV distance to 146.92 μm (1 μM), 142.77 μm (2 μM), and 148.99 μm (4 μM) at 72 hpf.
Decreased normal intersegmental vessel numbers to 86.96% (2 μM) and 88.41% (4 μM) of control at 72 hpf.
Decreased subintestinal vessel areas to 67.16% (0.5 μM), 61.19% (1 μM), 64.18% (2 μM), and 52.24% (4 μM) of control at 72 hpf.
Increased common cardinal vein areas to 1.14-fold (0.5 μM), 1.62-fold (1 μM), 1.80-fold (2 μM), and 3.26-fold (4 μM) of control at 72 hpf.
Decreased endothelial cell migration from caudal hematopoietic tissue to 82.29% (0.5 μM), 71.36% (1 μM), 62.09% (2 μM), and 61.26% (4 μM) of control at 72 hpf.
Increased ROS fluorescence intensity to 6.02-fold of control (0.5 μM) at 120 hpf.
Decreased SOD activity to 64.36% (0.5 μM) and 49.02% (1 μM) of control at 24 hpf.
Decreased CAT activity to 76.07% (1 μM) of control at 24 hpf.
Decreased GSH production to 74.73% (1 μM) of control at 24 hpf.
Increased MDA content to 1.52-fold (0.5 μM) and 1.61-fold (1 μM) of control at 24 hpf.
Increased acridine orange fluorescence intensity to 1.35-fold (0.5 μM), 1.31-fold (1 μM), 1.67-fold (2 μM), and 1.62-fold (4 μM) of control at 120 hpf.
Increased 8-OHdG content to 14.75-fold of control (4 μM) at 24 hpf.
Up-regulated DLL4 (1.38-fold) and VEGFC (1.33-fold), down-regulated CDH5 (47.81%) and VEGFA (44.74%) of control, up-regulated BAX (6.52-fold), P53 (1.56-fold), and CASPASE 3 (1.54-fold), and increased BAX/BCL-2 ratio to 6.12-fold of control for 1 μM at 24 hpf.
Up-regulated BAX (2.70-fold) and increased BAX/BCL-2 ratio to 2.57-fold of control for 0.5 μM at 24 hpf.
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Animal Model:F344/KIST male rats (7-week-old) treated with saline instead of DEN as the initiator[10]
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Dosage:25 μg/kg
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Administration:i.p.; twice weekly; 10 weeks
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Result:Reduced left liver lobe weight to 0.90 g (week 8), 0.45 g (week 10), 0.81 g (week 12), 0.25 g (week 15), and 0.67 g (week 22) compared to control values of 2.61 g, 3.17 g, 3.17 g, 3.10 g, and 3.34 g respectively.
Reduced caudate liver lobe weight to 0.03 g (week 10), 0.08 g (week 12), 0.16 g (week 15), and 0.07 g (week 22) compared to control values of 0.56 g, 0.56 g, 0.44 g, and 0.76 g respectively.
Increased right liver lobe weight to 3.23 g (week 12), 3.37 g (week 15), and 4.10 g (week 22) compared to control values of 2.04 g, 2.49 g, and 2.08 g respectively.
Increased middle liver lobe weight to 4.47 g (week 8), 4.97 g (week 10), 4.38 g (week 12), 6.26 g (week 15), and 7.33 g (week 22) compared to control values of 2.85 g, 3.92 g, 3.92 g, 3.54 g, and 3.85 g respectively.
Inhibited whole liver protein phosphatase 1 (PP1) and 2A (PP2A) activity to 29.3% of control (week 12) and 50.1% of control (week 15), with persistently lower activity in left liver lobe than right liver lobe through week 22.
Increased palmitoyl-CoA oxidase activity to 0.81 nmole/min/mg protein (week 4), 2.22 nmole/min/mg protein (week 8), 2.19 nmole/min/mg protein (week 10), 2.91 nmole/min/mg protein (week 12), and 2.01 nmole/min/mg protein (week 15) compared to control activity of 0.41 nmole/min/mg protein.
Increased microsomal cytochrome P-450 4A1 (CYP4A1) expression in left and right liver lobes.
Induced pro-apoptotic protein Bcl-Xₛ expression in left liver lobe from week 4 to week 15, with transiently increased anti-apoptotic Bcl-Xₗ expression at week 4 then return to control levels.
Induced persistent anti-apoptotic Bcl-Xₗ expression in right liver lobe with no detectable Bcl-Xₛ expression.
Caused broad fibrosis and atrophy in left liver lobe, and transient peri-central necrosis in right liver lobe that regenerated to normal by 10 weeks after treatment cessation.
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Animal Model:7-week-old male Fischer 344 (F344/KIST) rats were given a single intraperitoneal injection of N‑nitrosodiethylamine (DEN (HY-N7434), 200 mg/kg body weight) as an initiator at week 0, and administrations were started from week 3 after initiation[10]
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Dosage:25 μg/kg
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Administration:i.p.; twice weekly; 10 weeks
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Result:Blocked liver lobe atrophy and induced hypertrophy of all four liver lobes, with left lobe weight measuring 1.73 g (week 4), 1.83 g (week 8), 3.60 g (week 10), 3.44 g (week 12), 3.09 g (week 15), and 4.53 g (week 22) compared to control values of 2.25 g, 2.61 g, 3.17 g, 3.17 g, 3.10 g, and 3.34 g respectively.
Inhibited PP1/PP2A activity initially, with activity recovering to 52.7% of control (week 12) and 78% of control (week 15).
Increased palmitoyl-CoA oxidase activity to 0.89 nmole/min/mg protein (week 4), 1.20 nmole/min/mg protein (week 8), 1.29 nmole/min/mg protein (week 10), and 1.22 nmole/min/mg protein (week 12) compared to control activity of 0.41 nmole/min/mg protein, with levels lower than in saline-initiated nodularin-treated rats.
Induced microsomal cytochrome P-450 4A1 (CYP4A1) expression relative to controls with some variation.
Induced persistent anti-apoptotic Bcl-Xl expression across all liver lobes, with no Bcl-Xs induction.
Promoted adenoma formation in liver tissue.
Chemical Information
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CAS No. 118399-22-7
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Appearance Solid
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Molecular Weight 824.96
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Formula C41H60N8O10
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Color White to off-white
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Structure Classification
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Initial Source
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Purity & Documentation
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Data Sheet (306 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Nodularin Related Classifications
HY-P2040 Related Classifications
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- Nodularin
- 118399-22-7
- Phosphatase
- Apoptosis
- Caspase
- Bcl-2 Family
- p38 MAPK
- Ribosomal S6 Kinase (RSK)
- Reactive Oxygen Species (ROS)
- CLC cells
- primary rat hepatocytes
- Fischer 344 rats
- primary common carp HK leukocytes
- zebrafish (Danio rerio)
- protein phosphatase 2A
- protein phosphatase 1
- hepatocellular carcinoma
- mouse liver
- HepG2 cells
- Inhibitor
- inhibitor
- inhibit