Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.
Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy.
Bianchi
R
R
Mario Negri Institute for Pharmacological Research, Milan, Italy.
Triban
C
C
Marini
P
P
Figliomeni
B
B
Paro
M
M
Italiano
G
G
Prosdocimi
M
M
Fiori
M G
MG
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000032:analysis; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014630:Vagus Nerve / Q000201:enzymology*
D001786:Blood Glucose; D017301:Ca(2+) Mg(2+)-ATPase; D005677:G(M1) Ganglioside; D005732:Gangliosides; D006442:Glycated Hemoglobin; D000254:Sodium-Potassium-Exchanging ATPase