Post-mortem biochemistry of beagle dog lenses after treatment with Fluvastatin (Sandoz) for 2 years at different dose levels.
Post-mortem biochemical analyses of dog lenses and of aqueous humour of a 2 year oral toxicity study in the dog with Fluvastatin (control, 1, 8 and 16 mg/kg/day) did not show any relationship to the observed lens opacities (3 animals out of 8 at 16 mg/kg/day). With respect to lens transparency, a daily dosage of 8 mg/kg/day Fluvastatin to dogs over a period of 2 years is non-cataractogenic. Mean data on lenticular enzyme activities (GPX, G6PH, GAPDH, ALD, AR, LDH, PFK and SDH) as well as measurements of GSH/GSSG, ATP, ADP, AMP, Gluc, Fruc, Sorb, G6P and F6P do not indicate changes which may directly lead to lens opacifications. Conformational changes of lens proteins (heat lability of PFK-activity), a shift in the albumin/IgG ratio of aqueous humour and equatorial lens protein composition changes (after isoelectrofocusing) were observed. The biological significance of these changes is unknown as the non-cataractogenic dose for lens opacities in beagle dogs is 8 mg/kg/day.
Hockwin
O
O
Department of Experimental Ophthalmology, University of Bonn, FRG.
Evans
M
M
Roberts
S A
SA
Stoll
R E
RE
D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D001082:Aqueous Humor / Q000737:chemistry; D002386:Cataract / Q000139:chemically induced* / Q000201:enzymology; D003459:Crystallins / Q000378:metabolism; D004285:Dogs; D004798:Enzymes / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000633:toxicity*; D005260:Female; D000077340:Fluvastatin; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007211:Indoles / Q000633:toxicity*; D007908:Lens, Crystalline / Q000737:chemistry*; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism
D000924:Anticholesteremic Agents; D003459:Crystallins; D004798:Enzymes; D005136:Eye Proteins; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D010732:Phosphofructokinase-1; D005978:Glutathione