bendazac-lysine and Cataract

Bendazac is an oxyacetic acid with anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties, but its principal effect is to inhibit the denaturation of proteins. The lysine salt, which is better absorbed than the parent compound after oral administration, has been evaluated as a treatment for cataract, a condition which appears to result mainly from the denaturation, aggregation and precipitation of proteins within the lens. Results from a very small number of preliminary studies using objective photographic and densitometric methods have suggested that oral bendazac lysine, usually at a dosage of 500 mg 3 times daily, can stabilise the progression of lens opacification in patients with cataract. Significant improvements in individual and mean visual acuities in treated patients have been reported by several studies, but this parameter is not universally accepted as a reliable index of lens status. Preliminary studies evaluating bendazac lysine 0.5% eyedrops have reported comparable results to those obtained with oral treatment. Overall, tolerability of the drug has been good in studies to date. A dose-related laxative effect and other gastrointestinal disturbances are the most common adverse effects associated with oral therapy, and a transient burning sensation is the most commonly reported symptom occurring with eyedrop application. Bendazac lysine is one of a number of agents which have been introduced for the management of cataract. Although the results of preliminary studies have suggested that the drug may be useful for delaying the progression of cataract, further clinical studies using proven objective methods are required to fully establish its value in the management of this condition and its long term tolerability.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cataract; Humans; Indazoles; Pyrazoles; Rabbits

In connection with the clinical trial of an anti-cataract drug (Bendazac lysine) a number of examination methods were used to assess the progress of the cataract: slitlamp examination, visual acuity determination, and the measurement of the contrast sensitivity, light scatter in the eye and the autofluorescence and transmission of the lens. In this article the measurements of 43 patients (43 eyes) are presented, taken at the time that medication was started. In this way we can get an impression of the value of these measurements for the study of cataractous lenses. The contrast sensitivity of the cataractous eye is lowered for all spatial frequencies as compared with the normal population. Light scatter is greatly increased. The autofluorescent profile of the lens with nuclear cataract differs markedly from that of the lens with cortical cataract.

Topics: Aged; Aged, 80 and over; Cataract; Contrast Sensitivity; Female; Humans; Indazoles; Lens, Crystalline; Light; Male; Middle Aged; Photography; Scattering, Radiation; Visual Acuity

A double-masked placebo-controlled clinical trial with hard data evaluation by image analysis of Scheimpflug photographs taken at baseline and 6, 12 and 18 months after starting treatment was performed to assess the efficacy of bendazac lysine in four different types of senile cataract. The study had a classical split-plot design. For statistical evaluation, the analysis of variance and covariance for repeated measures were used for three different lens sections: anterior capsule and superficial layer, anterior cortex and nucleus. In the entire group of 53 evaluable patients (without separation into cataract-type subgroups), there was a significantly less increase over time in light scattering (i.e. film blackening) of the anterior cortex and nucleus with bendazac lysine than with placebo. There was also a strong trend in favour of the active drug at the anterior capsular level. Patients with water clefts and spokes showed a significantly less light scattering of the anterior capsule and cortex when treated with bendazac lysine. Those with nuclear changes also showed significantly less light scattering of the anterior cortex and nuclear region with the active drug than with placebo. The number of patients with subcapsular and wedge-shaped (cuneiform) cataracts was too small to be adequately assessed by statistical procedures. Nevertheless, there were indications of a beneficial effect of bendazac lysine on all the lens sections in patients with subcapsular cataracts and on the anterior cortical region in those with wedge-shaped cataracts. In conclusion, this study showed that the increase in light scattering over time, i.e. the progression of cataract, is less in bendazac lysine-treated patients than in those treated with placebo.

Topics: Adult; Aged; Cataract; Clinical Trials as Topic; Densitometry; Drug Administration Schedule; Female; Humans; Image Processing, Computer-Assisted; Indazoles; Lens Capsule, Crystalline; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Male; Middle Aged; Photography; Pyrazoles; Random Allocation; Time Factors

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cataract; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Indazoles; Male; Middle Aged; Pyrazoles; Random Allocation; Tablets; Visual Acuity

We describe here the development of potent synthetic analogues of the naturally occurring triterpenoid lanosterol to reverse protein aggregation in cataracts. Lanosterol showed superiority to other scaffolds in terms of efficacy and generality in previous studies. Various modified lanosterol derivatives were synthesized via modification of the side chain, ring A, ring B, and ring C. Evaluation of these synthetic analogues draws a clear picture for SAR. In particular, hydroxylation of the 25-position in the side chain profoundly improved the potency, and 2-fluorination further enhanced the biological activity. This work also revealed that synthetic lanosterol analogues could reverse multiple types of mutant-crystallin aggregates in cell models with excellent potency and efficacy. Notably, lanosterol analogues have no cytotoxicity but can improve the viability of the HLE-B3 cell line. Furthermore, representative compound 6 successfully redissolved the aggregated crystallin proteins from the amyloid-like fibrils in a concentration-dependent manner.

Topics: Cataract; Cell Survival; Cells, Cultured; Crystallins; HeLa Cells; Humans; Lanosterol; Lens, Crystalline; Mutant Proteins; Mutation; Protein Aggregation, Pathological; Structure-Activity Relationship

Novel bendazac analogues and their salts have been designed and prepared. The resulting compounds (13c-d, 15c, 17c) showed very good aqueous solubility (>100 mg/mL). An in vitro assay showed that most of the resulting compounds had potent protective activity against the oxidative damage. Particularly, compound 13d was also able to enhance the WSP and T-AOC level in the H(2)O(2)/FeCl(3)-induced oxidative damage model, indicating the resulting compound may protect the lens through an antioxidant pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cataract; Indazoles; Lens, Crystalline; Oxidative Stress; Rabbits; Rats; Solubility

The lysine salt of bendazac is a non-steroidal anti-inflammatory agent, and it is marketed exclusively for the treatment of cataracts. We report two cases of possible hepatotoxicity due to the use of bendazac lysine.. Laboratory tests, serologic tests, abdominal sonography and scan were performed to study liver disease.. Reversible increases of the hepatic enzymes were found in both cases. Anemia was also found in one of the cases (case 1).. Abnormal liver test results could be related to a possible liver injury attributed to the use of bendazac lysine.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cataract; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Indazoles; Liver Function Tests

The racemization of amino acids is hypothesized to cause cataract by disrupting the crystalline's tertiary structure, which, in turn, alters the optical characteristics of the lens. To better understand the role of these modifications in cataractogenesis, the changes in stereoisomer ratio of amino acids from lens crystalline by UV-B-induced cataract in animal models were studied using chiral separation gas chromatography-single quadrupole mass spectroscopy. The anticataract action of a compound, ([1-(phenylmethyl)-1H-indazol-3-yl]oxy)acetic acid lysinate, was also evaluated by this method.

Topics: Amino Acids; Animals; Anti-Inflammatory Agents; Cataract; Crystallins; Gas Chromatography-Mass Spectrometry; Indazoles; Lens, Crystalline; Male; Radiation Injuries, Experimental; Rats; Stereoisomerism; Steroids; Ultraviolet Rays

The study is based upon the fact that aging processes inevitably affect all parts of the human body. These processes are often followed by pathological changes, whose basic cause may be some of the genetic factors or insufficient and inadequate nutrition, but they may also be intensified by the influence of adverse effects in the work place or ecologic factors. It is often impossible to completely avoid the impact of all these processes upon the human body, but the application of certain preventive measures and medicamentous therapy may diminish or slow them down. The results of the application of various medicaments with the purpose of slowing down the manifestation or progress of cataract have shown that such measures of the medicamentous prevention of cataract certainly have medical justification. It has also been found that the medicaments applied slowed down the development and progress of lens opacities and the occurrence of cataract to a higher or lesser degree, depending on the kind of preparation and its efficacy.

Topics: Adult; Aged; Aspartic Acid; Cataract; Drug Combinations; Female; Humans; Indazoles; Inosine Monophosphate; Male; Middle Aged; Niacinamide; Parabens; Thimerosal; Visual Acuity

A modified Zeiss slit lamp coupled with a digital image-processing system was used to evaluate objectively changes in lens transparency over 1 year at 4-month intervals in 150 eyes of 92 patients affected by early senile cataract. A total of 59 patients were treated daily with 1.5 g bendazac-lysine, and 33 patients constituted the control group. At follow-up, visual acuity was also tested using Snellen letter charts at variable contrast to provide an additional parameter closer to traditional methods. Results indicate that the minimal angle of resolution at 10% contrast (MAR10) and the mean gray-level value of the lens image obtained by retroillumination (MLR) are sensitive to early changes in lens transparency. Using MAR10 as a parameter, the control group showed a significant, progressive worsening of the lens status over 12 months, whereas the treated group exhibited no significant changes. MRL indicated the same behaviour as MAR10, although lens damage was detected later in the control group. The results show that bendazac-lysine may delay the formation of lens opacities.

Topics: Aged; Aged, 80 and over; Aging; Cataract; Contrast Sensitivity; Densitometry; Female; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Indazoles; Interferometry; Lens, Crystalline; Light; Male; Middle Aged; Pyrazoles; Visual Acuity

Authors describe the in vitro effect of bendazac-L-lysine salt on the activity of enzyme aldose reductase from rat lens. In the presence of bendazac the activity of the tested enzyme was inhibited. Lineweaver-Burk plot demonstrated that the inhibition was noncompetitive. The possible curative effects on diabetic cataract together with a better way of administration are pointed out.

Topics: Aldehyde Reductase; Animals; Cataract; Indazoles; Kinetics; Lens, Crystalline; Pyrazoles; Rats; Sugar Alcohol Dehydrogenases

The medical treatment of cataract now appears to be a distinct possibility. A number of anti-cataract formulations are being clinically tested, and more clinical trials are being planned. To obtain a true assessment of a drug's efficacy, a battery of tests are needed which can accurately assess cataract progress. A clinical trial of the proposed anti-cataract drug Bendalina is being conducted. The six subjective methods used to assess cataract progression in the trial are presented. These are refractive error, LogMAR visual acuity, contrast sensitivity, glare sensitivity, retinal visual acuity and displacement threshold hyperacuity. The reasons for using each technique and their method of measurement is explained.

Topics: Aged; Cataract; Contrast Sensitivity; Humans; Indazoles; Macular Degeneration; Refractive Errors; Scattering, Radiation; Sensory Thresholds; Visual Acuity

The effects of bendazac-L-lysine salt (bendazac-lysine) on some biochemical parameters (soluble and insoluble proteins, reduced glutathione, sulphydryl and disulphide groups, water content) in rabbit lens at different times after X-rays (2000 rads) were studied. The mature cataract (swelling and total lens opacity) developed 11-12 weeks after irradiation. In the mature cataract, the irradiated lenses not treated with bendazac-lysine (ILNTB) show a 32% increase in water content compared with controls; this increase is 12% in irradiated lens treated with bendazac-lysine (ILTB). Twelve weeks after irradiation the concentration of insoluble proteins in the controls, ILNTB and ILTB is 7.6%, 52.3% and 18.3% respectively. After 6, 8 and 12 weeks the concentration of reduced glutathione in ILNTB decreases by 23%, 81% and 92% as compared with the controls. In the ILTB the decrease is present only 8 and 12 weeks after X-irradiation and is of 55% and 69%, respectively. The sulphydryl-group content in the soluble proteins in ILNTB compared with the controls decreases by 26%, 38% and 47% after 6, 8 and 12 weeks, while in the ILTB a decrease is observed only after 8 and 12 weeks and is 6% and 12%, respectively. The decrease of the sulphydryl groups parallels the increase of the disulphide groups. This increase is already significant (P less than 0.01) after 6 weeks in the ILNTB, whereas it becomes significant in the ILTB only after 8 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cataract; Chromatography, Gel; Crystallins; Dithiothreitol; Dose-Response Relationship, Radiation; Glutathione; Indazoles; Lens, Crystalline; Molecular Weight; Organ Size; Pyrazoles; Rabbits; Time Factors; Water

Bendazac, as such or in the form of its l-lysine salt, has a protective effect against lens protein denaturation both in vitro and in vivo. In vitro this effect has been documented on the lens proteins of rats, rabbits and pigs by using nephelometry, electrophoresis and electron microscopy. In vivo the protective effect has been observed after treatments ranging in duration from 3 to 14 days depending on the dosage used; the minimal effective dose produced a serum level of 35 micrograms/ml of bendazac. The penetration of the drug into the lens has been shown by both radioassay and HPLC; the lens concentration of bendazac increases with the duration of treatment. The mechanism of the protective action of bendazac against lens protein denaturation is discussed together with the implications of such protective action in the treatment of cataract.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Cataract; Crystallins; Indazoles; Lens, Crystalline; Microscopy, Electron; Protein Denaturation; Pyrazoles; Rats