Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer's Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13.

Alzheimer's disease (AD) is a major type of dementia disorder. Common cognitive changes occur as a result of cerebrovascular damage (CVD) via the disruption of matrix metalloproteinase-13 (MMP-13). In diabetic cases, the progress of vascular dementia is faster and the AD rate is higher. Patients with type 2 diabetes are known to have a higher risk of the factor for AD progression. Hence, this study is designed to investigate the role of astaxanthin (AST) in CVD-associated AD in zebrafish via the inhibition of MMP-13 activity. CVD was developed through the intraperitoneal and intracerebral injection of streptozotocin (STZ). The AST (10 and 20 mg/L), donepezil (1 mg/L), and MMP-13 inhibitor (i.e., CL-82198; 10 µM) were exposed for 21 consecutive days in CVD animals. The cognitive changes in zebrafish were evaluated through light and dark chamber tests, a color recognition test, and a T-maze test. The biomarkers of AD pathology were assessed via the estimation of the cerebral extravasation of Evans blue, tissue nitrite, amyloid beta-peptide aggregation, MMP-13 activity, and acetylcholinesterase activity. The results revealed that exposure to AST leads to ameliorative behavioral and biochemical changes. Hence, AST can be used for the management of AD due to its multi-targeted actions, including MMP-13 inhibition.

Therapeutic Investigation of Palm Oil Mill Effluent-Derived Beta-Carotene in Streptozotocin-Induced Diabetic Retinopathy via the Regulation of Blood-Retina Barrier Functions.

Diabetic retinopathy (DR) primarily progresses into retinal degeneration caused by microvascular dysfunction. The pathophysiology of DR progression is still uncertain. This study investigates the function of beta-carotene (PBC) originating from palm oil mill effluent in the treatment of diabetes in mice. An intraperitoneal injection of streptozotocin (35 mg/kg) was used to induce diabetes, which was then accelerated by an intravitreal (i.vit.) injection of STZ (20 µL on day 7). PBC (50 and 100 mg/kg) and dexamethasone (DEX: 10 mg/kg) were also administered orally (p.o.) for 21 days. At various time intervals, the optomotor response (OMR) and visual-cue function test (VCFT) responses were evaluated. Biomarkers, such as reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARSs), and catalase activity were determined in retinal tissue samples. DR significantly lowers the spatial frequency threshold (SFT) and time spent in the target quadrant (TSTQ), increases the reaching time in the visual-cue platform (RVCP), lowers retinal GSH and catalase activity levels, and elevates TBARS levels. The treatments of PBC and DEX also ameliorate STZ-induced DR alterations. The potential ameliorative activity of PBC in DR is attributed to its anti-diabetic, anti-oxidative, and control of blood-retinal barrier layer properties.

Reversal of Neuralgia Effect of Beta Carotene in Streptozotocin-Associated Diabetic Neuropathic Pain in Female Zebrafish via Matrix Metalloprotease-13 Inhibition.

Beta carotene is a natural anti-oxidant agent, and it inhibits the matrix metalloprotease (MMP) activity. Diabetic neuropathic pain (DNP) is produced by cellular oxidative stress. The role of the beta carotene effect in diabetic neuropathic pain is not explored yet. The present study is designed for the evaluation of the palm oil mill effluent-derived beta carotene (PBC) effect in DNP in zebrafish. The DNP was induced by the intraperitoneal administration of streptozotocin (STZ). Blood glucose levels of above 15 mM were considered to be diabetic conditions. The zebrafish were exposed to test compound PBC (25, 50, and 100 µM), pregabalin (PG: 10 µM), and an MMP-13 inhibitor (CL-82198; 10 µM) for 10 consecutive days from day 11. The neuralgic behavioral parameters, i.e., temperature test, acetic acid test, and fin clip test were assessed on day 0 and the 7th, 14th, and 21st days. On the 22nd day, the blood glucose and MMP-13 levels and brain thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and MMP-13 activity levels were estimated. The treatment of PBC ameliorated the DNP-associated behavioral and biochemical changes. The results are similar to those of PG and CL-82198 treatments. Hence, the PBC possesses a potentially ameliorative effect against DNP due to its potential anti-oxidant, anti-lipid peroxidation, and MMP-13 inhibitory actions.

Preventive Action of Beta-Carotene against the Indoxyl Sulfate-Induced Renal Dysfunction in Male Adult Zebrafish via Regulations of Mitochondrial Inflammatory and ß-Carotene Oxygenase-2 Actions.

Indoxyl sulfate (IS) is a metabolic byproduct of indole metabolism. IS readily interacts with the mitochondrial redox metabolism, leading to altered renal function. The ß-carotene oxygenase-2 (BCO2) enzyme converts carotenoids to intermediate products. However, the role of ß-carotene (BC) in IS-induced renal dysfunction in zebrafish and their modulatory action on BCO2 and mitochondrial inflammations have not been explored yet. Hence, the present study is designed to investigate the role of BC in the attenuation of IS-induced renal dysfunction via regulations of mitochondrial redox balance by BCO2 actions. Renal dysfunction was induced by exposure to IS (10 mg/L/hour/day) for 4 weeks. BC (50 and 100 mg/L/hour/day) and coenzyme Q10 (CoQ10; 20 mg/L/hour/day) were added before IS exposure. BC attenuated the IS-induced increase in blood urea nitrogen (BUN) and creatinine concentrations, adenosine triphosphate (ATP), and complex I activity levels, and the reduction of renal mitochondrial biomarkers, i.e., BCO2, superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), reduced and oxidized glutathione (GSH/GSSG) ratio, and carbonylated proteins. Moreover, renal histopathological changes were analyzed by the eosin and hematoxylin staining method. As a result, the administration of BC attenuated the IS-induced renal damage via the regulation of mitochondrial function.