Novel antioxidant astaxanthin-s-allyl cysteine biconjugate diminished oxidative stress and mitochondrial dysfunction to triumph diabetes in rat model.

AIMS: The present study determines the effect of administration of novel antioxidant astaxanthin-s-allyl cysteine biconjugate (AST-SAC) against streptozotocin-induced diabetes mellitus (DM) in rats. MAIN METHODS: AST-SAC (1 mg/kg/day) was treated against DM in rats for 45 days. The oxidative stress, antioxidants level, insulin secretion, activities of various carbohydrate metabolizing enzymes were studied. The glucose uptake in L6 myotubes was studied. In addition, in silico analysis of interaction of AST-SAC with proteins such as insulin receptor (IR) and 5'-adenosine monophosphate-activated protein kinase (AMPK) were carried out. KEY FINDINGS: Administration of AST-SAC in DM rats has protected the mitochondrial function (decreased oxidative stress and normalized oxidative phosphorylation activities) and antioxidant capacity of the pancreas which has resulted in beta cells rejuvenation and insulin secretion restoration. AST-SAC decreased the alpha-glucosidases activities to bring glycemic control in DM rats. Due to these effects the glycoprotein components and lipids were restored to near normalcy in DM rats. AST-SAC protected the antioxidant status of liver, kidney and plasma; and curbed the progression of secondary complications of DM. AST-SAC treatment stimulated glucose uptake in L6 myotubes in in vitro. To support this observation, AST-SAC interacted with proteins such as IR and AMPK in silico. SIGNIFICANCE: AST-SAC can be considered as "multi-target-directed ligand", that is, through these manifold effects, AST-SAC has been able to prevail over DM in rats.

Alteration of paraoxonase, arylesterase and lactonase activities in people around fluoride endemic area of Tamil Nadu, India.

BACKGROUND: Toxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world. METHODS: We collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5' triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, δ-ALAD) activities. RESULTS: In fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase - AChE and adenosine 5' triphosphatase - ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity. CONCLUSION: The toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor.