Apamin

Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is known to block Ca2+-activated K+ channels and prevent carbon tetrachloride-induced liver fibrosis.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Peptides

Research Areas >> Neurological Disease

Natural Products >> Others

K+ channel[1]

Apamin is an 18 amino acid peptide neurotoxin found in apitoxin (bee venom). It has long been known as a specifically selective blocker of Ca2+-activated K+ (SK) channels. Apamin inhibits liver fibrosis in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced mouse model as determined by hematoxylin and eosin staining. Apamin treatment attenuates inflammatory cytokine expression, including IL-6, IFN-γ, TNF-α and IL-1β compared with expression levels in the DDC-fed group[1]. Apamin is an 18 amino acid peptide neurotoxin found in apitoxin (bee venom). Apamin, a neurotoxin extracted from bee venom, specifically binds to a particular class of Ca2+-activated K+ channels which are involved in the slow afterhyperpolarization (S-AHP) that follows action potentials in many excitable cell[2].

To investigate the anti-fibrotic effect of Apamin on ECM deposition in the DDC-fed mice, Liver fibrosis induced by DDC is confirmed by induction of fibrogenic genes, FSP-1, α-smooth muscle actin (α-SMA) and collagen I expression. Expression of α-SMA is strongly expressed in the myofibroblasts and HSCs around the proliferated bile duct in the DDC-fed group and clearly with the Apamin treatment. Moreover, expression of collagen I in the DDC-fed group is significantly increased, especially in the portal tracts[1].

HSC-T6 cells, an immortalized rat hepatic stellate cell line, which has a stable phenotype and biochemical characteristics. Cells are cultured at 37°C in a humidified incubator under a 5% CO2 atmosphere. HSC-T6 cells are seeded in complete medium for 24 h. The cells are changed to fresh serum-free media containing the indicated concentrations of Apamin (0.5, 1 and 2 µg/mL). After 24 h, the cells are replaced with fresh serum-free media containing 2 ng/mL of TGF-β1 for 24 h[1].

Mice[1] For induction of liver injury, 8-week-old C57BL/6 male mice (20-25 g) are selected. Male C57BL/6 mice are fed a control diet or a DDC supplemented diet (0.1%) for 4 weeks to induce advanced biliary fibrosis. The mice receive an intraperitoneal injection of Apamin (0.1 mg/kg) dissolved in saline twice a week. Mice are sacrificed after 4 weeks from the first DDC diet administration.

[1]. Kim JY, et al. Apamin suppresses biliary fibrosis and activation of hepatic stellate cells. Int J Mol Med. 2017 May;39(5):1188-1194.

[2]. Messier C, et al. Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes. Brain Res. 1991 Jun 14;551(1-2):322-6.

Nigericin sodium salt | Senicapoc | E-4031 | 4-AMINOPYRIDINE | Ginsenoside Rg3 | TRAM-34 | Dofetilide | PAP-1 | Minoxidil | Flufenamic Acid | Flupirtine maleate | NS-1619 | Endoxifen (Z-isomer hydrochloride) | NS309 | Quinine

MOLECULAR FORMULA :

C79-H131-N31-O24-S4

MOLECULAR WEIGHT :

2027.65

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3800 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 22,308,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2900 ug/kg

TOXIC EFFECTS :

Behavioral - ataxia

REFERENCE :

EJBCAI European Journal of Biochemistry. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1967- Volume(issue)/page/year: 56,35,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Behavioral - changes in motor activity (specific assay)

REFERENCE :

NSAPCC Naunyn-Schmiedeberg's Archives of Pharmacology. (Springer Verlag, Heidelberger, Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.272- 1972- Volume(issue)/page/year: 300,189,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intracerebral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1800 ng/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 22,308,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 20,157,1982