allopurinol and Cataract

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Allopurinol; Anti-Bacterial Agents; Antimalarials; Cardiac Glycosides; Cataract; Child; Chloroquine; Chlorpromazine; Epinephrine; Ethambutol; Ethchlorvynol; Eye Diseases; Female; Humans; Miotics; Nalidixic Acid; Phosphates; Pilocarpine; Quinolines; Retinal Degeneration; Warfarin

The relationship between gout medication use and cataract development is controversial. Moreover, limited clinical studies have evaluated this relationship.. To assess the effects of colchicine, allopurinol and benzbromarone on the risk of cataract in patients with gout.. Population-based nested case-control study.. We enrolled 7900 patients who had received a new diagnosis of cataract >3 years after gout diagnosis into the study group and 33 475 patients who did not receive a diagnosis of cataract into the control group by matching for age, sex and the year of gout diagnosis at a ratio of 1:1. We used World Health Organization's defined daily dose (DDD) as a measure to assess the dosage of colchicine, allopurinol and benzbromarone exposure. Logistic regression was used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of cataract.. The risk of cataract significantly increased in patients who received colchicine at a cumulative DDD of ≥66.5 (OR = 1.17, 95% CI = 1.01-1.36, P = 0.041). In the age-stratified analysis, patients with gout aged >60 years had a higher risk of cataract (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011) than did patients aged <60 years. Allopurinol and benzbromarone had no association with cataract.. In this population-based nested case-control study, we observed that colchicine use increased the risk of cataract in patients with gout, especially in those aged >60 years who received colchicine at a cumulative DDD of >66.5.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Allopurinol; Benzbromarone; Case-Control Studies; Cataract; Colchicine; Databases, Factual; Female; Gout; Gout Suppressants; Humans; Logistic Models; Male; Middle Aged; National Health Programs; Risk Factors; Taiwan; Young Adult

Reactive oxygen species and lipid peroxidation are important factors that contribute to the development of age-related cataract. The study included 130 patients with age-related cataract, 69 of whom were diagnosed with hypertension (HT), 20 with hypertension and type 2 diabetes mellitus (DM), and 41 had no accompanying condition. The following parameters were measured in the serum of the examinees: products of lipid peroxidation malondialdehyde (MDA) and lipofuscin-like fluorophores (LLF), activity of prooxidative enzymes xanthine oxidase (XO) and myeloperoxidase (MPO), antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the concentration of thiol groups, and the ferric reducing activity of plasma. The activity of prooxidative enzymes XO and MPO was higher in the plasma of patients with HT (XO=9.0±1.2 U/L; MPO=77.3±8.4 U/L) and with HT and DM (XO=11.9±0.9 U/L; MPO=89.5±5.0 U/L) compared to patients with age-related cataract (XO=6.2±0.9 U/L; MPO=52.4±6.3 U/L; P<0.01). Our research has shown that patients with age-related cataract and hypertension were exposed to increased oxidative damage of biomolecules, based on the increased plasma LLF and MDA content and decreased levels of thiol groups. Oxidative changes of biomolecules in these patients were associated with increased activity of the XO, MPO, and GPx enzymes and a lower extracellular SOD activity and total ferric reductive ability of plasma.

Topics: Aged; Biomarkers; Cataract; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Male; Xanthine Oxidase

To evaluate effects of melatonin on sodium selenite-induced cataract formation.. Twenty-three Sprague-Dawley rat pups were randomized into three groups. Group 1(n = 9), injected with selenite (s.c.) on postpartum day 10; group 2 (n = 7), injected with selenite (s.c.) on day 10 plus melatonin (i.p.) on days 8-15; group 3 (n = 7), saline-injected controls. Development of cataract was assessed weekly under a dissection microscope. Rat lenses and serums were analyzed for antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT); oxidative stress indicators xanthine oxidase (XO) and malondialdehyde (MDA), a marker of lipid peroxidation; and protein carbonyl (PC), a marker of protein oxidation.. Significant differences (p < 0.05) were seen in cataract development by the three groups. All rats developed dense nuclear cataract in group 1. Dense nuclear cataract was not observed in group 2: five of seven rats developed minor cataracts, while the other two had clear lenses. In control rats (group 3), all lenses remained clear. In selenite group (group 1), lens and serum levels of MDA, PC, and XO were significantly higher and levels of SOD and CAT were significantly lower than those in control group (p < 0.001). In selenite+melatonin group (group 2), lens and serum levels of MDA, PC, and XO significantly decreased and levels of SOD and CAT significantly increased when compared with selenite group.. Studies with the rat selenite cataract model strongly support the activity of melatonin as an endogenous antioxidant and anticataract agent.

Topics: Animals; Animals, Newborn; Antioxidants; Catalase; Cataract; Disease Models, Animal; Lens, Crystalline; Lipid Peroxidation; Malondialdehyde; Melatonin; Oxidative Stress; Protein Carbonylation; Rats; Rats, Sprague-Dawley; Sodium Selenite; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Xanthine Oxidase

Wistar rat pups treated with curcumin, a natural constituent of Curcuma longa before being administered with selenium showed no opacities in the lens. The lipid peroxidation, xanthine oxidase enzyme levels in the lenses of curcumin and selenium co-treated animals were significantly less when compared to selenium treated animals. The superoxidase dismutase and catalase enzyme activities of curcumin and selenium co-treated animal lenses showed an enhancement. Curcumin co-treatment seems to prevent oxidative damage and found to delay the development of cataract.

Topics: Animals; Antioxidants; Catalase; Cataract; Curcumin; Enzyme Inhibitors; Lipid Peroxidation; Rats; Rats, Wistar; Selenium; Time Factors; Xanthine Oxidase

Biochemical evidence suggests that the oxidative damage of the lens proteins is involved in the genesis of senile cataract and the development of diabetes-related pathologic changes such as the formation of cataracts. In particular, lens proteins are subject to extensive oxidative modification. Oxidative damage either decreases the antioxidant capacity or decreased antioxidant capacity results in oxidative damage. The purpose of this study was to analyze the activities of the antioxidant enzymes such as Cu,Zn Superoxide Dismutase (Cu,Zn-SOD) and catalase in the cataractous lenses of the type 2 diabetic group and cataractous lenses of the senile group.. Eighteen diabetic cataractous lenses and twenty six senile cataractous lenses were studied. Cu,Zn-SOD activity was measured in lenses by enzymatic method and catalase activity was measured by colorimetric method.. Cu,Zn-SOD levels were significantly lower in the diabetic cataractous lenses than senile cataractous lenses (respectively 8.052 +/- 0.818, 18.216 +/- 4.217 microg/g prot. p < 0.05). Similarly, catalase levels were significantly lower in the diabetic cataractous lenses than senile cataractous lenses (respectively 0.326 +/- 0.134, 0.665 +/- 0.322 kU/g prot. p < 0.001).. The results of the present study indicate that the antioxidant capacity in the diabetic cataractous lenses were decreased and this result suggests a role of antioxidant enzymes in the genesis of diabetic cataracts.

Topics: Aged; Antioxidants; Catalase; Cataract; Diabetes Mellitus, Type 2; Female; Glutathione; Humans; Lens, Crystalline; Male; Middle Aged; Molybdenum; Superoxide Dismutase; Xanthine Oxidase

The activities of the protective enzymes, superoxide dismutase, catalase, glutathione peroxidase and of xanthine oxidase, an enzyme acting as a source of O(-)(2), were measured in the lenses of alloxan-induced diabetic and control rats. Superoxide dismutase and glutathione peroxidase activities were found to be significantly decreased, while catalase and xanthine oxidase activities were increased. This means that the ratio of the oxidant/antioxidant enzymes increases in the diabetic rat lens, suggesting an increased oxidative stress. This imbalance is possibly an important contributing factor in the pathogenesis of diabetic cataract.

Topics: Animals; Catalase; Cataract; Diabetes Mellitus, Experimental; Female; Glutathione Peroxidase; Lens, Crystalline; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Xanthine Oxidase

To determine whether exposure to allopurinol is associated with an increased risk of cataract extraction in elderly patients.. We conducted a case-control study using data from the Quebec universal health insurance program for all elderly patients. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21,868 controls were randomly selected among patients not diagnosed with cataract and matched to cases on the date of the extraction. We determined the odds ratio of cataract extraction according to the cumulative dose and duration of allopurinol use relative to nonusers, using conditional logistic regression analysis. The analysis was adjusted for the effects of age, sex, diabetes mellitus, hypertension, glaucoma, and ophthalmic and oral corticosteroid exposure.. A cumulative dose of allopurinol of more than 400 g or a duration of use of longer than 3 years were associated with an increased risk of cataract extraction, with odds ratios of 1.82 (95% confidence interval [CI], 1.18-2.80) and 1.53 (95% CI, 1.12-2.08), respectively. No increase in risk was observed for lower cumulative doses or shorter exposure periods.. Long-term administration of allopurinol increases the risk of cataract extraction in elderly patients.

Topics: Aged; Aged, 80 and over; Allopurinol; Case-Control Studies; Cataract; Cataract Extraction; Confidence Intervals; Female; Gout Suppressants; Humans; Lens, Crystalline; Male; Odds Ratio; Quebec; Risk Factors; Time Factors; Universal Health Insurance

This study was conducted to search for xanthine oxidase inhibitors in natural products obtained from plants collected in Puerto Rico and to assess the influence of these extracts in the prevention of cataractogenesis.. Allopurinol is currently a xanthine oxidase inhibitor used in the treatment of gout. New alternatives with increased therapeutic activity and less side effects should be investigated. Preclusion of cataractogenesis in diabetic rats is also the focus of this investigation. Natural products in the form of plant extracts from Puerto Rico offer a rich and relatively untapped source for the discovery of new drugs that may address these kind of problems.. Nineteen collections of Myrtaceae plant extracts were screened for xanthine oxidase inhibition. A spectrophotometrical method was used employing allopurinol as positive control and a blank as negative control. A protocol of the assay with slight modifications was followed from the literature. Two extracts with the highest percentages of xanthine oxidase inhibition were evaluated for possible prevention of cataractogenesis in streptozotocin diabetic rats. The animals were given to drink these plant extracts ad libitum for three months while controls received water. The appearance of cataracts was assessed physically.. Two of the nineteen plant extracts showed high inhibition percentages of xanthine oxidase. Eucalyptus deglupta and Syzygium malaccense displayed 51% and 64% inhibitions (IC50 44.5 micrograms/ml and IC50 51 micrograms/ml), respectively. As for the cataractogenesis inhibition, laboratory animals that drank E. deglupta for three months did not develop cataracts.. Two plant extracts provided positive results with varying degrees of inhibition of xanthine oxidase. S. malaccense demonstrated the greatest xanthine oxidase inhibitory activity whereas E. deglupta presented the best finding for cataractogenesis prevention. The procedures used in this investigation are useful for the in vitro screening of xanthine oxidase inhibition and the in vivo evaluation of cataractogenesis prevention.

Topics: Allopurinol; Animals; Cataract; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Eucalyptus; Medicine, Traditional; Phytotherapy; Plant Extracts; Plants, Medicinal; Puerto Rico; Rats; Rats, Sprague-Dawley; Spectrophotometry; Xanthine Oxidase

Topics: Allopurinol; Cataract; Humans

Rats fed a high galactose (30% galactose) diet (w/w) or made diabetic by injecting streptozotocin developed mature cataracts in approximately 45 and 90 days, respectively. Addition of allopurinol, a commonly used drug in the therapy of gout, to the high galactose diet or to the normal diet fed to diabetic rats advanced cataractogenesis in both the groups by approximately 50%. Allopurinol fed to control rats did not cause cataract formation. Feeding butylated hydroxy toluene (BHT), an antioxidant, prevented the allopurinol-induced advancement of cataract formation in galactosemic and diabetic rats. Assuming that these results are applicable in human subjects, there is need for caution in using allopurinol for the therapy of gout in diabetic subjects.

Topics: Allopurinol; Animals; Butylated Hydroxytoluene; Cataract; Diabetes Mellitus, Experimental; Diet; Galactose; Galactosemias; Lipid Peroxidation; Male; Rats; Rats, Inbred Strains

Several reports have suggested an association between chronic allopurinol ingestion and cortical and subcapsular cataract formation. To examine this possibility we identified 51 allopurinol users and compared their lenses with those of 76 patients who did not use allopurinol. The existence of lens opacities and the level of visual acuity were assessed by review of medical records or by prospective ophthalmic examinations; in both phases of the study the examiners were blinded as to the patient's use or non-use of allopurinol. Three different outcomes were considered: formation of any cataract, formation of a posterior subcapsular cataract, and formation of a cataract contributing to a corrected visual acuity of 20/30 or worse. The risk ratio for the formation of any cataract was 1.3 (95% confidence interval: 0.8, 2.0), the risk ratio for the formation of a posterior subcapsular cataract was 0.9 (0.3, 2.0), and the risk ratio for the formation of a cataract contributing to a loss of visual acuity was 1.3 (0.6, 2.9). None of these risk ratios was changed appreciably after controlling for age, sex, hypertension, or diabetes. Thus, after a mean of 6.9 years of allopurinol use, we found no evidence to confirm that allopurinol users were at higher risk of acquiring cataracts.

Topics: Allopurinol; Cataract; Female; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Risk Factors; Visual Acuity

We have shown that an unusual morphological thinning of the anterior clear zone of the lens is found in patients with gout on long term Allopurinol therapy. The significance of this is discussed.

Topics: Adult; Aged; Aged, 80 and over; Allopurinol; Cataract; Gout; Humans; Lens, Crystalline; Male; Middle Aged; Sunlight

10 types of drugs in current use believed to induce cataracts are identified and the evidence of their role is presented. Allopurinol, an antihyperuricemic used to treat gout, may induce cataracts in young subjects after longterm treatment. Experimental results suggest a relationship between the rate of circulating allopurinol, the extent of exposure to ultraviolet light, and perhaps individual susceptibility. Amiodarone hydrochloride is a benzofurane derivative used to combat cardiac arrhythmia since 1960. Cataracts are infrequently observed in users and the complication may be encouraged by association with other medications. Use of anticholinesterasics to treat chronic or acute glaucoma leads to cataracts in 20-50% of cases according to different workers. The rate is about the same for all anticholinesterasics but may be higher in older subjects. The drugs should not be used if the tension can be controlled by parasympathicomimetics and epinephrine or perhaps carbon anhydrase inhibitors. If they are used, the patient should be carefully examined every 6 months for vacuoles. The smallest possible dose should be used. Synthetic antimalarials, the chelator deferoxamine, inorganic mercury, and the phenothiazines have all been associated with cataract formation. The risk of cataracts associated with corticoids increases with the amount of the daily dose and the duration of treatment, with individual susceptibility apparently also playing a role. Sex is not a factor but young children may be at greater risk. Among the cytostatics, the alkylants have been implicated in development of ocular lesions, although the metaphase inhibitor vincristine has been shown in vitro to be responsible for cataracts as well. There is some evidence that diphenyl hydantoine used with phenobarbitol to treat epilepsy may induce cataracts. Some cases of cataracts have been reported in young women using combined oral contraceptives (OCs) for whom no other etiology was found. The implicated OCs had higher hormonal contents than those currently in use. A prospective study by Faust and Tyler did not uncover any evidence of the etiologic role of OCs, but elsewhere a case was reported in which evolving cataracts were stabilized on termination of OC use. Another study found no increase in opacities after 6 months of treatment with OCs. Experimental evidence of a link was found in rabbits but the doses were so high that they cannot be considered to confirm a toxic effect

Topics: Adrenal Cortex Hormones; Allopurinol; Amiodarone; Animals; Antimalarials; Antineoplastic Agents; Antipsychotic Agents; Cataract; Cholinesterase Inhibitors; Contraceptives, Oral, Hormonal; Deferoxamine; Humans; Mercury; Phenothiazines; Phenytoin; Prednisone

Topics: Allopurinol; Animals; Cataract; Eye Protective Devices; Humans; Middle Aged

We conducted a two-part study to determine whether any positive association between the use of allopurinol and the development of cataracts could be demonstrated. Study 1 included 251 Boston-area patients hospitalized for cataract and 753 matched controls. Two cataract patients were regular allopurinol users as compared with six control patients. The relative risk for cataract comparing allopurinol users with nonusers was 1.0 (95% exact confidence interval 0.14, 4.7). Study 2 included 389 patients from the Puget Sound, Washington, area who were hospitalized for cataract surgery during a five-year period (551,543 person-years). The rate of hospitalization for cataract in patients 30 to 49 years old was 0/992 person-years for allopurinol users and 78/366,960 (2.1 per 10(4)) person-years for nonusers. The rate of hospitalization for cataract in patients 50 to 64 years old was 3/2,270 (13.2 per 10(4)) person-years for allopurinol users and 308/184,583 (16.7 per 10(4)) person-years for nonusers.

Topics: Allopurinol; Cataract; Humans

We examined 11 cataractous lenses (or aspirated lens matter from extracapsular extractions) from patients ranging in age from 55 to 84 years who used allopurinol on a long-term basis (more than two years). Phosphorescence analyses demonstrated the characteristic allopurinol triplet in these lenses. When we analyzed normal lenses from patients taking allopurinol in a similar manner we found no evidence of allopurinol photobinding. These data indicated that allopurinol has a cataractogenic action only in patients in whom the drug has become photobound within the lens. Long-term allopurinol therapy does not necessarily cause or enhance cataracts in all patients. There may be a relationship between ultraviolet radiation exposure and circulating allopurinol levels (and perhaps renal function) in the genesis of photosensitized allopurinol cataracts.

Topics: Aged; Allopurinol; Cataract; Gout; Humans; Lens, Crystalline; Middle Aged; Spectrometry, Fluorescence; Time Factors; Ultraviolet Rays

The National Registry of Drug-Induced Ocular Side Effects has accumulated 30 cases of suspected allopurinol-induced lens changes. The cataracts associated with this antihyperuricemic agent are initially anterior and posterior lens capsule changes with anterior subcapsular vacuoles. With time, wedge-shaped anterior and posterior cortical haze occurs, along with dense posterior subcapsular cataracts. Histologic studies of these cataracts showed no unique or identifying features. These cases do not prove a cause-and-effect relationship, but raise the suspicion that allopurinol may be cataractogenic in some patients. Additional case reports and lens material should be sent to the National Registry of Drug-Induced Ocular Side Effects, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97201.

Topics: Adult; Aged; Allopurinol; Cataract; Cataract Extraction; Female; Gout; Humans; Lens, Crystalline; Male; Middle Aged

Long-term ingestion of allopurinol, an antihyperuricemic agent used to treat gout, may be related to the development of lens opacities in relatively young patients (second to fifth decades of life). Cataracts obtained from three patients taking allopurinol were subjected to high-resolution phosphorescence spectroscopy. The characteristic allopurinol triplet was demonstrated in all three cataracts. Identical spectra were obtained for normal human lenses incubated in media containing 10(-3)M allopurinol and exposed to 1.2 mW/cm2 ultraviolet radiation for 16 hours; control lenses (irradiated without allopurinol) showed no allopurinol triplets. Similar data were obtained for lenses from rats given one dose of allopurinol and exposed to ultraviolet radiation overnight. These data provide evidence that allopurinol can be photobound in rat and human lenses and suggest its cataractogenic potential.

Topics: Aged; Allopurinol; Animals; Cataract; Gout; Humans; Lens, Crystalline; Male; Middle Aged; Rats; Rats, Inbred Strains; Spectrum Analysis; Ultraviolet Rays