Intermittent Fasting and Vitamin E Supplementation Attenuates Hypothyroidism-Associated Ophthalmopathy.

Visualization is a complex-integrated procedure of the eyes and brain that allows to see this colorful world. Hypothyroidism-associated ophthalmopathy (HAO), often known as dry eyes, swelling around the eyes, blurred vision, glaucoma, and cataracts, are some eye-related issues caused by hypothyroidism. Yet there is no permanent cure for hypothyroidism; taking medicine throughout life is the only solution to keep its harmful effects under control. This study used intermittent fasting (IF) and vitamin E (Vit.E) supplementation to prevent hypothyroidism-associated ophthalmopathy. This study hypothesized that intermittent fasting-like diet regimens and vitamin supplementation should reduce the propagation of HAO by its antioxidant potential. In the present study, experimental animals are divided into five groups: normal, hypothyroidism control, dual, Vit. E, and IF. Hypothyroidism is generated in the experimental groups by taking propylthiouracil (PTU) for 24 days while also taking IF and Vit. E supplements. The hypothyroid-induced experimental animals demonstrated an increase in IOP and lipid peroxidation while thyroid hormone levels depicted a massive decline which is a clear denotation of the effects of the thyroid on eyes and lifestyle. Ancient Ayurveda inspires these proposed therapies and has successfully reduced all the damage to the thyroid gland and the eye.

The visual field-testing maze and vision maze: Feasible techniques to evaluate visual field loss in animals.

Visual field loss due to glaucoma is a severe and concerning problem, leading to limited visual range and poor quality vision. The progression of this loss begins with a para-central arcuate scotoma which eventually advances to a ring scotoma and constricted visual fields in later stages. Currently, no animal model is available for screening this pattern of vision loss. However, we have successfully developed two mazes to evaluate visual field loss - the visual field-testing maze (VFTZ) for peripheral vision loss and the vision maze (VM) for central vision loss. Our studies involved inducing glaucoma in Wistar and Sprague Dawley rats using lipopolysaccharide (LPS) and testing them in VFTZ and VM. We used Latanoprost and dorzolamide eye drops as standard drug candidates during the study. We evaluated the animals for intraocular pressure, retinal vasculature imaging, and anxiety using tonometry, ophthalmoscopy, and light and dark model techniques. Furthermore, we quantified the antioxidant parameters of the retina using UV spectroscopy. Our findings showed that animals with peripheral visual field loss in VFTZ took significantly more time to reach the goal and spent more time within the maze compared to normal or drug-treated animals (P < 0.001). Additionally, animals with compromised central visual field in VM spent more time in a particular arm and changed arms less frequently (P < 0.001) compared to normal or drug-treated animals. Moreover, we observed that glaucomatous rats exhibited elevated anxiety levels and impaired performance in the mazes, emphasizing the impact of vision loss on anxiety. Finally, the antioxidant and ATPase alterations in the retinal layers verified the glaucomatous changes in the experimental animals. Based on our remarkable findings, we strongly recommend the use of VFTZ and VM to evaluate visual field loss in animals.

Oxymatrine impedes the progression of endotoxin-induced glaucoma via redox system modulations.

This study aimed to provide irrefutable evidence of the preventive effects of oxymatine (OMT) on a model of endotoxin induced glaucoma in Wistar rats which can be attributed to its anti-inflammatory, antioxidant, and TNF-α antagonistic properties. To assess the impact of OMT on uveitic glaucoma, the normal group received 100 µL distilled water topically for 15 days, while the glaucoma control group was induced with uveitic glaucoma by applying 10 µL of 10 µg/mL lipopolysaccharide (LPS) topically for 3 consecutive days. The treatment groups were then given OMT solution at a volume of 50 µL with varying doses of 0.25%, 0.5%, and 1% once a day via topical administration for 15 days. In addition, as a standard, the animals were also given 100 µL of 1% dorzolamide topically for 15 days. All ophthalmic dosing was carried out by pulling the lower eye-lid of the experimental animals and administration of the respective solutions. The study uses cutting-edge real-time imaging of the retinal vasculature in anesthetized animals, postsacrifice lenticular picturization and biochemical evidence to support the changes in the retinal layers. LPS induced animals demonstrated increased IOP, disrupted antioxidant systems, massive lipid damage, enhanced TNF-α activity and changes in intracellular ATPase and ionic activities. The damaged retinal vasculature and lenticular opacification further supported the biochemical evidence. However, using OMT at a 1% dosage effectively enhanced the antioxidant levels, regulated intracellular ion concentration and ATPases, decreased TNF-α activity, and counteracted mechanobiological changes in the visual front and retina. Moreover, OMT can successfully normalize intraocular pressure, making it a highly beneficial treatment option for glaucoma.

Role of GLP-1 receptor agonist in diabetic cardio-renal disorder: Recent updates of clinical and pre-clinical evidence.

Cardiovascular complications and renal disease is the growing cause of mortality in patients with diabetes. The subversive complications of diabetes such as hyperglycemia, hyperlipidemia and insulin resistance lead to an increase in the risk of myocardial infarction (MI), stroke, heart failure (HF) as well as chronic kidney disease (CKD). Among the commercially available anti-hyperglycemic agents, incretin-based medications appear to be safe and effective in the treatment of type 2 diabetes mellitus (T2DM) and associated cardiovascular and renal disease. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to be fruitful in reducing HbA1c, blood glucose, lipid profile, and body weight in diabetic patients. Several preclinical and clinical studies revealed the safety, efficacy, and preventive advantages of GLP-1RAs against diabetes-induced cardiovascular and kidney disease. Data from cardio-renal outcome trials had highlighted that GLP-1RAs protected people with established CKD from significant cardiovascular disease, lowered the likelihood of hospitalization for heart failure (HHF), and lowered all-cause mortality. They also had a positive effect on people with end-stage renal disease (ESRD) and CKD. Beside clinical outcomes, GLP-1RAs reduced oxidative stress, inflammation, fibrosis, and improved lipid profile pre-clinically in diabetic models of cardiomyopathy and nephropathy that demonstrated the cardio-protective and reno-protective effect of GLP-1RAs. In this review, we have focused on the recent clinical and preclinical outcomes of GLP-1RAs as cardio-protective and reno-protective agents as GLP-1RAs medications have been demonstrated to be more effective in treating T2DM and diabetes-induced cardiovascular and renal disease than currently available treatments in clinics, without inducing hypoglycemia or weight gain.

Resveratrol attenuates behavioural impairment associated with learning and memory in rats with diabetes induced by a high-fat diet and streptozotocin.

BACKGROUND AND PURPOSE: A high-fat diet (HFD) is a common risk factor for Type 2 diabetes mellitus (T2DM) and its associated cognitive impairments. In models of diabetes, resveratrol, a modulator of SIRT1, regulates the fasting glucose and antioxidant levels, as well as the lipid profile. Resveratrol may also alleviate the cognitive dysfunctions associated with diabetes. EXPERIMENTAL APPROACH: Albino rats were fed a HFD, (60% kcal fat) after treatment with streptozotocin (45 mg·kg-1 ,i.p., single dose) to induce an experimental model of T2DM. After 14 weeks of the animals in confirmed diabetic condition, they were treated with metformin (200 mg·kg-1 ,i.p.) or resveratrol (50 or 100 mg·kg-1 ,i.p.) for 4 weeks. Levels of oxidative-nitroso-stress, SIRT1, TGF-ß1, inflammation and cholinergic activity were determined in plasma, hippocampus and cerebral cortex. A battery of behavioural studies associated with learning memory were performed during and after the experimental protocol. KEY RESULTS: Treatment with resveratrol attenuated the increased glucose levels (pre- and post-prandial), impaired glucose tolerance, HbA1c, and decreased the body weights of the T2DM rats. Moreover, resveratrol ameliorated the impaired learning and memory associated with increased SIRT1 and decreased TGF-ß1, TNF-α, oxidative-nitroso-stress, and cholinergic activities in the plasma and the brains of the T2DM animals. CONCLUSION AND IMPLICATION: Our results demonstrated that SIRT1 modulation interacted with TGF-ß1 signalling, and mitigated hyperglycaemia and subsequent learning-memory impairments in the T2DM animals. Our study also suggested novel therapeutic targets, including TGF-ß1, which may add to our knowledge of resveratrol, when used to treat impaired memory associated with diabetes.

Potential role of IP3/Ca2+ signaling and phosphodiesterases: Relevance to neurodegeneration in Alzheimer's disease and possible therapeutic strategies.

Despite large investments by industry and governments, no disease-modifying medications for the treatment of patients with Alzheimer's disease (AD) have been found. The failures of various clinical trials indicate the need for a more in-depth understanding of the pathophysiology of AD and for innovative therapeutic strategies for its treatment. Here, we review the rational for targeting IP3 signaling, cytosolic calcium dysregulation, phosphodiesterases (PDEs), and secondary messengers like cGMP and cAMP, as well as their correlations with the pathophysiology of AD. Various drugs targeting these signaling cascades are still in pre-clinical and clinical trials which support the ideas presented in this article. Further, we describe different molecular mechanisms and medications currently being used in various pre-clinical and clinical trials involving IP3/Ca+2 signaling. We also highlight various isoforms, as well as the functions and pharmacology of the PDEs broadly expressed in different parts of the brain and attempt to unravel the potential benefits of PDE inhibitors for use as novel medications to alleviate the pathogenesis of AD.

Protective effect of Coleus forskohlii leaf-extract compound on progression of cataract against Fructose-Induced experimental cataract in rats.

The present study was designed to determine protective effects of Coleus forskohlii hydroalcoholic leaf-extract along with its fractions against fructose-induced cataract rat model. The Coleus forskolii leaf extract was subjected to silica gel column chromatography and fractions were collected. A major high yielding fraction of the leaf extract, designated as fraction B6 was pharmacologically evaluated in Sprague Dawley albino rats at three doses 0.1, 1 and 10 mg/kg respectively. Compound B2; isolated from B6 fraction, identified as 'gallic acid' was also pharmacologically evaluated at three different doses. Cataract was induced by concurrent administration of fructose solution (10% w/v, per oral, dissolved in drinking water) for eight consecutive weeks. Mean arterial pressure, blood glucose level and lenticular opacity were determined. At the end of eight weeks, C. forskohlii leaf extract fraction and gallic acid reduced mean arterial pressure and glucose level in a dose dependent manner. In addition, C. forskohlii led to significant restoration of lens antioxidants enzyme level and reduced cataract formation in rats. These results showed the concentration dependent protective effect by C. forskohlii leaf extract against cataract formation due to restoration of oxidative stress markers.

Topical Administration of ACE Inhibitor Interrupts the Progression of Cataract in Two Kidney One Clip Induced Hypertensive Cataract Model.

PURPOSE: Previously, we assessed that hypertension increases cataractogenesis. In the present study, we evaluated the effect of oral and topical administration of enalapril on two kidney one clip (2K1C)-induced hypertensive cataract model by evaluating the biochemical alteration of lenticular antioxidants, ionic content, ATPase activity, protein content and careful examination of the lenticular opacity. MATERIALS AND METHOD: Animals were divided into normal and hypertensive animals. Hypertensive animals were divided into hypertensive control group (0.3% CMC), enalapril (oral) treatment group (20 mg/kg/day; p.o), and enalapril (topical) treatment group (0.1% w/v on the eye cornea) for a period of twelve weeks. During experimental study blood pressure, heart rate and morphology of the eyes were monitored biweekly. After twelve weeks, lenses were photographed and various catractogenic biochemical parameters were assessed. RESULTS: Enalapril (oral) treatment conserved the blood pressure (systolic and diastolic), restored the level of antioxidants, restored the lipid peroxidation marker, nitrite content, ionic content, ATPase function, protein content, and thus delayed the cataract formation. While, enalapril (topical) treatment exhibited anti-cataract effect without affecting the systolic and diastolic blood pressure that could be by restoring the antioxidant level, maintaining the ionic balance, balancing the protein levels, and by inhibiting the upregulated ocular renin angiotensin system. The overall results suggest that enalapril (topical) treatment showed conspicuous effect than enalapril (oral) treatment in adjourning the cataract formation. CONCLUSION: Based on the results, it may be concluded that upregulated ocular RAS by increasing oxidative stress and by misbalancing the lenticular ionic and protein content may lead to cataract formation in hypertensive condition.

Role of the renin-angiotensin system in the development of cataract formation in angiotensin-II-induced experimental rats.

Previously, we established several facts regarding hypertension-associated cataractogenesis. As a follow-on study, we evaluated the role of the renin-angiotensin system (RAS) in angiotensin-II (Ang-II)-induced cataract formation in experimental hypertensive rats. Sprague-Dawley male albino rats (150-180 g) were used for the present experiment. The animals were divided into four groups, with six animals in each group. During the 12 weeks of the experimental protocol, the normal group received sterile water (1 ml/kg/day, subcutaneously (sc), and the Ang-II control group received angiotensin (1 mg/kg/day) subcutaneously. The ARB (O) group received olmesartan (2 mg/kg/day) orally, and the ARB (T) group received two drops of olmesartan (5 mM) topically on the cornea; concurrently, both groups were treated with Ang-II (1 mg/kg/day, sc) to induce hypertension. Biweekly, the systolic and the diastolic blood pressures were recorded, and the eyes were examined; moreover, cataractogenic parameters, such as oxidative stress markers and protein contents in the lenses, were evaluated after completion of the experimental protocol. Twelve weeks of olmesartan administered, orally or topically, significantly reduced the progression of cataract formation and restored antioxidants, lipid peroxidation, nitrite content, and protein contents in the lenses of the mice in groups O and T, respectively, as compared with those in the Ang-II control group. On the basis of our results, we conclude that the ocular RAS exacerbates the lenticular oxidative stress that may lead to cataract formation. The results showed that the RAS has an independent and important role in cataract formation under hypertensive conditions.

Oxymatrine Protects TGFß1-Induced Retinal Fibrosis in an Animal Model of Glaucoma.

Glaucoma has engulfed a huge population of the world into its claws of blindness as it remains asymptomatic until nearly 40% of the neurons are lost and the only option left is for patients to be subjected to symptomatic treatments or surgical methods, neither of which is completely effective in curing the disease as they do not restore the physiological dimensions at the neuronal level. Among the several factors that drive the pathophysiology of glaucoma, one is the involvement of fibrogenic factors, such as transforming growth factor ß (TGFß) which remodels the extracellular matrix (ECM) and, thus, the deposition of fibrotic material in the retina, resulting in the progression of primary open-angle glaucoma (POAG). The primary objectives of this study were to evaluate the protective effects of oxymatrine (OMT) in the steroid-induced glaucoma model in experimental rats and to determine the role of transforming growth factor ß1 (TGFß1) in the pathogenesis of glaucoma and its consequent inhibition due to the antioxidant and the antiinflammatory, and also the TGFß1 antagonistic, behavior of OMT. To that end, we experimentally elucidated the role of OMT, a TGFß1 antagonist, that is known to play antiinflammatory and antioxidant roles in the steroid-induced glaucoma model in experimental rats, and using the enzyme-linked immunosorbent assay (ELISA), we observed a direct inhibitory effect of OMT on the pathogenesis of glaucoma. The antioxidant and the antiinflammatory potentials of OMT were determined using several biochemical methods to determine the major antioxidants in the retinal layers, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and glutathione (GSH), along with the nitrite and the malondialdehyde (MDA) concentration levels. As a result, OMT was found to reduce the total protein content in the retinal layers, a correlation that has not been previously reported. Moreover, the impacts of OMT on the major governing ATPases, namely Na+/K+ ATPase and Ca2+ATPase, along with its impacts on the intracellular ionic concentrations of Na+, K+, and Ca2+, were determined and were found to point toward OMT, restoring homeostasis in glaucomatous animals. A clearer picture of the changes during the treatment was obtained using retinal images of the live animals and of the lenticular changes in the sacrificed animal; these images provided data on the pathological pathways leading to glaucoma inception and its consequent inhibition by OMT. The data reported in this study clearly indicate that OMT has a possible role in inhibiting the pathogenesis of glaucoma, and the data also permit the quantification of several biochemical parameters of concern.

Therapeutic effects of various renin angiotensin modulators on hyperglycemia-induced cataract formation in Sprague Dawley rats.

OBJECTS: Our previous research work reported the beneficial effects of angiotensin receptor blockers (ARBs) for the treatment of diabetes associated cataract which was induced by streptozotocin (STZ). The current study, evaluated the effects of topical administration of various renin angiotensin modulators on STZ-induced cataracts in rats. METHODS: Single dose of STZ (60 mg/kg, i.p.) was administered in the rats to induce diabetes. Animals were divided into normal and diabetic rats. Normal rats were administered with single dose of sodium citrate buffer (0.1 M, 10ml/kg, i.p.). Diabetic animals were divided into various treatment groups, each group contains six animals and received aliskiren, olmesartan, enalapril, and angiotensin 1-7 at a dose of 0.5% w/v topically on the cornea of the eye for a period of 8 weeks. During experimental protocol morphology of the eyes and lenticular opacity were monitored. Animals were sacrificed after 8 weeks of drug treatment, and various cataractogenic biochemical parameters were assessed. RESULTS: Topical administrations with aliskiren, enalapril, olmesartan, and angiotensin 1-7 showed non-significant alterations in the blood glucose level, but significantly decreased lenticular opacity, restored antioxidant level, restored MDA level and Nitrite content, and decreased the onset of cataract formation. CONCLUSION: Overall, our findings suggest that topical treatment with renin angiotensin modulators delayed the onset of diabetes-induced cataract formation.

Biochemical Evidence Indicates the Preventive Effect of Resveratrol and Nicotinamide in the Treatment of STZ-induced Diabetic Cataract.

PURPOSE: High glucose level is a strong initiator of both oxidative stress and DNA damage to various cellular proteins. This activates the poly ADP-ribose polymerase (PARP) enzyme, which is responsible for disturbing physiological energy metabolic homeostasis. The present study aimed to elucidate the association between stress and the PARP pathway by using resveratrol (RSV) and nicotinamide (NAM, PARP inhibitor) to treat diabetic cataract. METHOD: Albino rats were used for the experimental study. A single streptozotocin administration (55 mg/kg, i.p.) prompted diabetes in the animals. The experimental groups were the normal group (non-diabetic) and the diabetic groups: the diabetic control animals (group D), the diabetic animals treated with RSV at 40 mg/kg/day, i.p. (D+ RSV group), NAM at 100 and 300 mg/kg/day, i.p. (D+ NAM100, D+ NAM300 groups, respectively), and a combination of RSV and NAM i.p. (D+ RSV+NAM100 = Combi 1 group, D+ RSV+NAM300 = Combi 2 group). Glucose levels and the eyes were examined biweekly; various cataractogenic parameters in the lenses were examined after completion of the eight-week experimental protocol. RESULTS: Compared to diabetic control, RSV monotherapy significantly decreased hyperglycemia and other lenticular alterations. NAM at the high dose only showed beneficial effects without altering the blood glucose level, lenticular aldose reductase (AR) activity, and sorbitol content, primarily restored the lenticular NAD level and decreased oxidative stress in diabetic rats. These findings regarding NAM treatment indicate that a pathway other than the antioxidant defense system and the polyol pathway, which might be due to PARP inhibition, is involved in diabetic cataracts. Moreover, compared to RSV monotherapy, combination treatments were effective. CONCLUSION: These results indicate that hyperglycemia and oxidative-osmotic-nitrosative stress play central roles in the pathophysiology of diabetic cataracts. Moreover, our study also revealed that concurrent treatment with the RSV and NAM may prove useful in the pharmacotherapy of diabetes and its secondary complications such as cataract.

Resveratrol delay the cataract formation against naphthalene-induced experimental cataract in the albino rats.

Oxidative stress-induced toxicity plays a major role in ocular diseases such as retinal degeneration, age-related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)-induced age-related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca2+ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti-cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca2+ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs.

Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract.

OBJECTIVE: The present study investigated the anticataract activity of a novel isoflavonoid, isolated from stem bark of Alstonia scholaris, against fructose-induced experimental cataract. METHODS: The bioactivity of fractions extracted from A. scholaris, an isolated isoflavonoid (ASII) was screened using in vitro (goat lens) and in vivo (albino rats) experimental cataract models. For the in vivo evaluation, albino rats (12-15 weeks old) were divided into five groups (n = 6). Group I (normal) received 0.3% carboxymethyl cellulose solution (10 mL/[kg·d], p.o.). Group II (control) received 10% (w/v) fructose solution in their drinking water. Groups III-V received ASII at three different doses, 0.1, 1.0 and 10 mg/(kg·d), concurrently with 10% (w/v) fructose solution. Treatment was given daily for 8 consecutive weeks. During the protocol, systolic blood pressure, diastolic blood pressure, blood glucose level and lenticular opacity were monitored at 2-week intervals. Pathophysiological markers (catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione and malondialdehyde) in eye lenses were examined at the end of the 8-week treatment period. RESULTS: The results of in vitro study showed that A. scholaris extract and the active fraction (A3) reduced the lenticular opacity as compared to toxic control group. The in vivo study showed that 8-week administration of ASII (0.1, 1.0 and 10 mg/[kg·d], p.o.) led to significant reduction in blood pressure and blood glucose level and retarded the initiation and evolution of cataractogenesis, compared to the fructose-induced cataract model control. Additionally, ASII treatment led to significant improvement in lens antioxidants (catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione) and decreased lens malondialdehyde, compared to the control group (group II). CONCLUSION: Results revealed that administration of ASII played a crucial role in the reduction of cataract formation in diabetic and hypertensive models.

Magnesium taurate attenuates progression of hypertension and cardiotoxicity against cadmium chloride-induced hypertensive albino rats.

The present study was designed to evaluate the antihypertensive activity and cardioprotective effects of magnesium taurate against cadmium chloride (CdCl2)-intoxicated albino rats. Sprague Dawley male albino rats (120-150 g) were divided into five groups having six animals in each group. Hypertension and cardiotoxicity were induced in animals by administration of CdCl2 (0.5 mg/kg/day, i.p.) for four weeks. Magnesium taurate (2 and 4 mg/kg/day) was administered orally after induction of hypertension (after two weeks) in their respective groups concurrently with CdCl2 for next two weeks. Amlodipine (3 mg/kg/day, p.o.) was used as a standard and administered after induction of hypertension. Blood pressure was monitored biweekly by using non-invasive blood pressure system and biochemical parameters and histopathology of the heart were evaluated after four weeks of the experimental protocol. During the four weeks of the experimental protocol, the toxic control group showed significant elevation of systolic and diastolic blood pressure concomitant with augmentation of cardiotoxicity as indicated by reduction in myocardial antioxidants including glutathione peroxidase, catalase, superoxide dismutase, reduced glutathione and increased malondialdehyde level in heart as compared to the normal group. The oral administrations of magnesium taurate significantly restored the blood pressure, myocardial antioxidants and malondialdehyde level as compared to toxic control group. In addition, histopathological examination showed that magnesium taurate treatments substantially reduced the myocardial damages against CdCl2 treatment. The results suggest that magnesium taurate has prominent antihypertensive and cardioprotective activity via its potent antioxidant activity and can be used as a nutrition supplement to improve the cardiovascular health.

Losartan delays the progression of streptozotocin-induced diabetic cataracts in albino rats.

The ocular renin-angiotensin system has become an interesting target for ocular diseases because it has been implicated in various ocular diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, uveitis, and hypertensive cataracts. In the present study, we explored the effect of topically and orally administered losartan (an angiotensin receptor blocker) on streptozotocin-induced diabetic cataract in albino rats. Topical treatment with losartan modulated neither the blood glucose level nor the polyol content but oral treatment with losartan decreased both. Topical and oral treatment with losartan significantly increased the antioxidants (glutathione, glutathione peroxidase, superoxide dismutase, and catalase), decreased the lipid peroxidant malondialdehyde, and restored soluble protein, and insoluble protein and various ions (Na+ , K+ , and Ca2+ ) in the lens; however, topical treatment had a better effect than oral treatment. These findings demonstrate that topical administration of losartan significantly reduces the risk of cataract formation without affecting either the blood glucose level or polyol contents.

Role of Nitric Oxide in the Development of Cataract Formation in CdCl2-induced Hypertensive Animals.

PURPOSE: Previously we established a strong association of systemic hypertension with cataract formation. In the present study, we investigated the role of nitric oxide (NO) in the development of cataract formation in CdCl2-induced hypertensive animals. MATERIALS AND METHODS: Hypertension was induced in male albino rats by intraperitoneal administration of CdCl2 (0.5 mg/kg/day) for eight weeks. The NO modulators, 10 µM S-nitrosoglutathione (NO donor) and 1% w/v Nω-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) were applied topically once a day on the eye cornea during the experimental period. Amlodipine (3mg/kg/day) was used as a standard antihypertensive drug and administered orally. RESULTS: In the CdCl2 control group, mean arterial pressure was significantly increased along with augmentation of lens nitrite, opacity, and oxidative stress. The control of hypertension by amlodipine substantially restored lens nitrite and cataractogenic events. Moreover, topical application of L-NAME significantly alleviated the lens nitrite, opacity, antioxidants (GSH, CAT, SOD, and GPx), MDA, proteins, and ionic (Na+ and Ca2+) contents. Whereas, S-nitrosoglutathione topical application exacerbated these cataractogenic events without affecting hypertension as compared to CdCl2 control group. The findings demonstrated that NO donor exacerbates and NOS inhibitor alleviates the cataract formation in hypertensive condition. The control of hypertension also reduces the cataract formation with reduction of lens nitrite level. CONCLUSION: The overall findings suggested the strong correlation between NO and hypertension associated cataract formation. The elevation of lens nitrite (NO metabolite) is one of the key factors of augmentation of lenticular oxidative stress and cataract formation in the hypertensive condition.

Development of pharmacological screening method for evaluation of effect of drug on elevated pulse pressure and arterial stiffness.

INTRODUCTION: Elevated pulse pressure (PP) and amplification of arterial stiffness (AS) are responsible for various cardiovascular disease and deaths. Numerous investigations have identified that different antihypertensive agents influence PP and AS differently. None of the previous studies described any reliable animal model particularly to screen drugs having effects on PP and AS. In present study, we developed an animal model to screen such drugs particularly affecting PP and AS. METHODS: Elevation of PP and amplification of AS were induced in rats by uninephrectomy along with high salt intake (NaCl 4% w/v) for a period of six weeks, and weekly changes in body weight, PP, systolic, diastolic, mean pressure and pulse wave velocity (PWV) were estimated. After six weeks, collagen elastin ratio of aortic segment was estimated. Histomorphometry of abdominal aortic section of rats was done using trinocular microscope. RESULTS: After six weeks, uninephrectomized rats that were kept on high salt drinking water shown significant increase (P < 0.001) in MAP, PP and PWV indicates that hypertension along with elevated PP developed in rats, and increase in collagen/elastin ratio (P < 0.001) as well as PWV as compared to normal rats indicates the increase in AS. CONCLUSION: The development of condition of hypertension in conjunction with increase in PP and AS in rats can be used as in-vivo screening model to determine the potency of drugs for the treatment of hypertension or other cardiovascular diseases associated with high PP and AS.

Therapeutic targets of renin-angiotensin system in ocular disorders.

PURPOSE: To review current literature on the renin-angiotensin system (RAS)-mediated pathogenic mechanisms and therapeutic targets in ocular diseases. METHODS: A comprehensive literature survey was performed on PubMed, Scopus, and Google Scholar databases published from 1977 to 2016. The search terms were a RAS, angiotensin, angiotensin receptor, prorenin, pro (renin) receptor, angiotensin converting enzyme inhibitor, angiotensin receptor blocker associated with ocular disorders like cataract, glaucoma, diabetic retinopathy (DR), macular degeneration, and uveitis. Articles were reviewed on the basis of the association between ocular disorders and RAS and relevant articles were discussed. RESULTS: The literature revealed that the individual RAS components including renin, angiotensins, angiotensin converting enzymes, and RAS receptors have been expressed in the specific ocular tissues like retina, choroid, and ciliary body. The activation of both circulatory and local RAS potentiate the various inflammatory and angiogenic signaling molecules, including vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase, and advanced glycation end products (AGE) in the ocular tissues and leads to several blinding disorders like DR, glaucoma, and macular degeneration. The classical and newer RAS inhibitors have illustrated protective effects on blinding disorders, including DR, glaucoma, macular degeneration, uveitis, and cataract. CONCLUSIONS: The RAS components are present in the extrarenal tissues including ocular tissue and have an imperative role in the ocular pathophysiology. The clinical studies are needed to show the role of therapeutic modalities targeting RAS in the treatment of different ocular disorders.

Magnesium taurate prevents cataractogenesis via restoration of lenticular oxidative damage and ATPase function in cadmium chloride-induced hypertensive experimental animals.

Previously we found that hypertension potentiates the risk the cataractogenesis. In the present study, we investigated the protective effects of magnesium taurate (MgT) on hypertension and associated lenticular damages against cadmium chloride (CdCl2)-induced hypertensive animals. Male Sprague-Dawley albino rats (150-180g) were assigned to five experimental groups (n=6). Among the five groups, normal group received 0.3% carboxymethyl cellulose (10ml/kg/day, p.o.). Hypertension control group received CdCl2 (0.5mg/kg/day, i.p.). Tests and standard groups received MgT (3 and 6mg/kg/day, p.o.) and amlodipine (3mg/kg/day, p.o.) concurrently with CdCl2 respectively, for six consecutive weeks. Blood pressure, heart rate, and eyes were examined biweekly, and pathophysiological parameters in serum and eye lenses were evaluated after six weeks of the experimental protocol. The chronic administration of MgT concurrently with CdCl2 significantly restored the blood pressure, serum and lens antioxidants (CAT, SOD, GPx, and GSH), MDA level, and ions (Na+, K+, and Ca2+). Additionally, MgT treatment led to significant increase in the lens proteins (total and soluble), Ca2+ ATPase, and Na+K+ ATPase activity as compared to hypertension control group. Ophthalmoscope observations indicated that MgT treatments delayed the progression of cataract against the hypertensive state. The study shows that MgT prevents the progression of cataractogenesis via restoration of blood pressure, lenticular oxidative damages, and lens ATPase functions in the hypertensive state. The results suggest that MgT supplement may play a beneficial role to manage hypertension and associated cataractogenesis.