From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Tue Dec 22 1998 - 15:55:12 MST
Looks like pyrazinoylguanidine is greatly superior to aminoguanidine in
the prevention of cataracts. It might be the guanidine of choice for the
purpose of life extension as well.
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Citations: 1-2
<1>
Authors
Follansbee MH. Beyer KH Jr. Vesell ES.
Institution
Department of Pharmacology, Pennsylvania State University College of
Medicine, Hershey 17033, USA.
Title
Studies on pyrazinoylguanidine. 6. Prevention of cataracts
in STZ-diabetic rats.
Source
Pharmacology. 54(5):256-60, 1997 May.
Abstract
This study was designed to determine whether pyrazinoylguanidine (PZG) can
attenuate cataract development in streptozotocin
(STZ)-induced diabetic rats. After a single, intraperitoneal dose of STZ (45
mg/kg in 0.05 mol/l sodium citrate buffer), Sprague-Dawley rats (250-260 g)
were divided into three groups. Beginning a week later, each group of
diabetic rats received twice daily for 24 weeks by gavage one of the
following: vehicle (saline 10 ml/kg), PZG (35 mg/kg), or captopril (15
mg/kg). PZG treatment prevented the development of diabetic
cataracts (p = 0.0009 compared to vehicle). In contrast to
PZG, 38% of vehicle-treated rats exhibited cataracts after
12 weeks, increasing to 89% after 16 weeks. At week 16, 22% of
captopril-treated rats exhibited cataracts, a 75% reduction
from vehicle-treated rats (p = 0.4289 compared to vehicle; p = 0.0571
compared to PZG). These results indicate that captopril can attenuate
cataract formation in STZ-diabetic rats, whereas PZG
completely suppresses it.
<2>
Authors
Swamy-Mruthinti S. Green K. Abraham EC.
Institution
Department of Biochemistry and Molecular Biology, Medical College of Georgia,
Augusta 30912, USA.
Title
Inhibition of cataracts in moderately diabetic rats by
aminoguanidine.
Source
Experimental Eye Research. 62(5):505-10, 1996 May.
Abstract
The effect of aminoguanidine (AG), an inhibitor of advanced glycation, on the
development of cataracts was studied in diabetic rats. Rats
were made diabetic with streptozotocin, and based on the level of plasma
glucose they were grouped as moderately (< 350 mg dl-1 plasma glucose) and
severely (> 350 mg dl-1 plasma glucose) diabetic. One half of the animals in
each group received AG (25 mg kg-1 body weight each day), intraperitoneally,
starting from the day of streptozotocin injection. Progression of lens
opacification was recorded using Fundus and Scheimpflug photography at
regular time intervals. On the ninetieth day all the rats were killed and the
levels of advanced glycation end products (AGE) was determined by measuring
the non-tryptophan fluorescence of the lens soluble and insoluble fractions.
Densitometric analysis of Scheimpflug images showed that in diabetic rats
lens opacification progressed in a biphasic manner, an initial slow
progression for the first 60 days, followed by a steep increase during next
30 days. Moderately and severely diabetic rats developed lens opacities more
or less at the same time. AGE fluorescence in the lens soluble fractions
increased three-fold and seven-fold in the moderately and severely diabetic
rats, respectively; whereas in insoluble fractions there was a 30% and
three-fold increase in the moderately and severely diabetic rats,
respectively. Although AG treatment inhibited the AGE fluorescence of lens
soluble and insoluble fractions by about 56% and 75% in moderately diabetic
and by 19% and 52% severely diabetic rats, respectively, the development of
cataracts was delayed only in the moderately diabetic rats.
These results thus suggest that the effect of AG is indeed inhibition of the
formation of AGEs. However, in the severely diabetic rats the beneficial
effect of AG is overwhelmed by the excessive accumulation of AGEs.
(diet seems to be important too.....)
<3>
Authors
Tavani A. Negri E. La Vecchia C.
Institution
Istituto di Ricerche Farmacologiche Mario Negri, Universita di Milano, Italy.
Title
Food and nutrient intake and risk of cataract.
Source
Annals of Epidemiology. 6(1):41-6, 1996 Jan.
Abstract
The relationship between cataract extraction and diet was
considered in a case-control study conducted in northern Italy. A total of
207 patients who had cataract extraction and 706 control
subjects in a hospital for acute, nonneoplastic, nonoculistic, nondigestive
tract diseases were interviewed during their hospital stay. Odds ratios (ORs)
and their 95% confidence intervals (CIs), according to the intake of alcohol,
coffee, tea, and cola, and frequency of intake of 34 food items and 8
micronutrients were derived from multiple logistic regression equations,
including terms for age, sex, education, smoking status, body mass index,
diabetes, and total calorie intake. Alcohol, coffee, decaffeinated coffee,
tea, and cola intakes were not associated with cataract
extraction. Among food items, reduced ORs for cataract
extraction (highest tertile of intake compared to the lowest), with a
significant inverse trend in risk, were found for intake of meat (OR 0.6, 95%
CI 0.4 to 0.9), cheese (OR 0.7, 95% CI 0.5 to 1.0), cruciferae (OR 0.5, 95%
CI 0.3 to 0.8), spinach (OR 0.6, 95% CI 0.4 to 0.9), tomatoes (OR 0.5, 95% CI
0.4 to 0.8), peppers (OR 0.7, 95% CI 0.4 to 1.1), citrus fruit (OR 0.5, 95%
CI 0.2 to 1.3), and melon (OR 0.5, 95% CI 0.4 to 0.8). A significant increase
in risk was found for the highest intake of butter (OR 2.8, 95% CI 1.2 to
6.4), total fat (OR 1.8, 95% CI 1.2 to 2.8), and salt (OR 2.4, 95% CI 1.4 to
4.0) compared to the lowest, and for consumption of oil other than olive oil
(OR 1.6, 95% CI 1.1 to 2.2). Among micronutrients, lower ORs for
cataract extraction (highest quintile of intake compared to
the lowest) were found for intake of calcium (OR 0.5, 95% CI 0.3 to 0.8),
folic acid (OR 0.4, 95% CI 0.2 to 0.7), and vitamin E (OR 0.5, 95% CI 0.3 to
1.0), while estimated intakes of methionine, retinol, beta-carotene, and
vitamins A, C, and D were not associated. Thus, this study indicates that
diet plays a considerable role in the risk of cataract
extraction in this Italian population, with a protective action played by
some vegetables, fruit, calcium, folic acid,and vitamin E, and an increased
risk associated with elevated salt and fat intake.
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