Deepali Jat

Chronic alcoholism refers to the unpleasant symptoms directly resulting from excessive drinking. Increased alcohol metabolites and an unbalanced oxidative state are likely to blame for the reported effects under these circumstances. According to preclinical and clinical research, vitamin B12 can act on several organ systems with demonstrated neuroprotective, antioxidant, and glutamate modulating properties. This research sought to examine the ameliorative effects of vitamin B12 (VtB12) in persistent alcohol (AlOH) exposed adult zebrafish with the help of following parameters like the anxiety related behavior test, Oxidative stress, and antioxidant assays, histological and immunofluorescence analysis. Zebrafish pretreated with 0.40% AlOH (v/v) for 120min (+AlOH) or not (-AlOH), were exposed for 6 hours to home tank water (-VtB12) or to 59µg-VtB12/kg-fish food (+VtB12) to analyze anxiety behavior in the geotaxis (novel tank) test as well as the oxidative brain damage in the adult zebrafish. Adult zebrafish exposed to chronic AlOH showed a decrease in the distance travelled, average and mobility speed, and increased the average frozen time, the explored area, and total no. of the site explored in the trapezoid tank. AlOH exposure also resulted in oxidative damage, enhanced lipid peroxidation, advanced oxidative protein products, decreased enzymatic and non-enzymatic antioxidant activities, and enhanced reactive oxygen species generation. Additionally, VtB12 supplementation improved neurogenesis, evident in increased Nissl cell numbers and NeuN expression in the brain. Chronic alcoholism may be effect on the brain cells as well as on the neuro-behavior of zebrafish. This research demonstrated that VtB12 shows promise as a neuroprotective agent against chronic alcoholism induced alterations in zebrafish's brain.

Aluminum chloride (AlCl₃) is a potent neurotoxic substance known to cause memory impairment and oxidative stress‐dependent neurodegeneration. Naringenin (NAR) is a dietary flavonoid with potent antioxidant and anti‐inflammatory properties which was implemented against AlCl₃‐induced neurotoxicity to ascertain its neuroprotective efficacy. Experimental neurotoxicity in mice was induced by exposure of AlCl₃ (10 mg/kg, p.o.) followed by treatment with NAR (10 mg/kg, p.o.) for a total of 63 days. Assessed the morphometric, learning memory dysfunction (novel object recognition, T‐ and Y‐maze tests), neuronal oxidative stress, and histopathological alteration in different regions of the brain, mainly cortex, hippocampus, thalamus, and cerebellum. AlCl₃ significantly suppressed the spatial learning and memory power which were notably improved by administration of NAR. The levels of oxidative stress parameters nitric oxide, advanced oxidation of protein products, protein carbonylation, lipid peroxidation, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and the activity of acetylcholine esterase were altered 1.5–3 folds by AlCl₃ significantly. Treatment of NAR remarkably restored the level of oxidative stress parameters and maintained the antioxidant defense system. AlCl₃ suppressed the expression of neuronal proliferation marker NeuN that was restored by NAR treatment which may be a plausible mechanism. NAR showed therapeutic efficacy as a natural supplement against aluminum‐intoxicated memory impairments and histopathological alteration through a mechanism involving an antioxidant defense system and neuronal proliferation.

Environmental aluminum intoxication has shown increasingly alarming negative consequences on reproductive health. This needs mechanistic exploration and preventive management using medicines like herbal supplementation. The ameliorative effects of naringenin (NAR) against AlCl₃-induced reproductive toxicity were thus evaluated in this study by assessing testicular dysfunction in albino male mice. A group of mice was treated with AlCl₃ (10 mg/kg b.w./day) and then with NAR (10 mg/kg b.w./day) for a total of sixty-two days. Results show that treatment of AlCl₃ significantly reduced the body weight and testis weight of mice. AlCl₃ caused oxidative damage in mice as evidenced by an increase in the concentration of nitric oxide, advanced oxidation of protein product, protein carbonylation, and lipid peroxidation. Furthermore, diminished activity of antioxidant moieties included superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione, and oxidized glutathione. Several histological changes, such as spermatogenic cell degeneration, germinal epithelium detachment, and structural abnormalities in seminiferous tubules, were observed in AlCl₃-treated mice. Oral administration of NAR was found to restore body weight and testes weight and ameliorated reproductive dysfunctions. NAR decreased oxidative stress, replenished the antioxidant defense system, and improved histopathological alterations in the AlCl₃-treated testes. Therefore, the present study suggests that the supplementation of NAR may be a beneficial strategy to mitigate AlCl₃-induced reproductive toxicity and testicular dysfunction.

Various studies suggested that neuroinflammation leads to the development of several neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Rotenone is an organic pesticide and potent inhibitor of complex I of electron transport chain widely used to develop the PD model. Numerous studies reported rotenone toxicity in the dopaminergic system but very few studies are available on rotenone‐induced glial cell activation and subsequent neurodegeneration and alterations in various types of behavior. Therefore, the present study was designed to explore the effect of rotenone on neuroinflammation and its deleterious effect on the behavior of mice, and also how these effects can be protected through quercetin. Quercetin, a natural flavonoid having strong antioxidant and anti‐inflammatory properties, is found in vegetables and fruits. The finding of the study indicated that rotenone 5 mg/kg body weight for 60 days through oral gavage leads to the release of inflammatory markers in blood serum, astrocytes activation in substantia nigra and hippocampus, and subsequently decreased density of dopaminergic fibers in the striatum. Rotenone also altered the memory of the mice as indicated by decreased spontaneous alteration in Y‐maze and T‐maze tests and reduction in exploration time in novel object recognition, increased immobility time in the forced swim test and reduced muscular strength. Co‐treatment of quercetin 30 mg/kg/day through oral gavage for 60 days along with rotenone significantly reversed all these adverse effects, suggesting that quercetin could reduce neuroinflammation, and improve memory, and cognitive function.

The present study investigated the protective effect of curcumin and mitochondrial‐targeted curcumin (MTC) in rotenone‐induced cerebellar toxicity in mice. Treatment of rotenone in mice significantly shortened the stride length for both forelimb and hind‐limb and increased fore‐paws and hind‐limb base width. Co‐treatment of curcumin and MTC with rotenone improved the walking pattern. A significant increase in lipid peroxidation, nitric oxide and decreased activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in rotenone‐treated mice while co‐treatment of curcumin and MTC with rotenone significantly increased AChE activity and protected against rotenone‐induced oxidative damage. Rotenone exposed mice showed irregular, damaged Purkinje cells and perineuronal vacuolation while co‐treatment of curcumin and MTC with rotenone protected against rotenone‐induced cellular damage in these cells. The result exhibits that both curcumin and MTC showed protective effects against rotenone‐induced cerebellar toxicity in mice and MTC is more effective than curcumin.

Background Mitochondrial impairments due to free radicals are implicated in a wide range of neurotoxicological alterations. Curcumin, an active ingredient of turmeric has shown protective efficacy against oxidative damage due to its strong antioxidant potential, but its efficiency is restricted due to low bioavailability in the mitochondria. In view of this, we have synthesized mitochondria-targeted curcumin (MTC) with an aim to investigate its efficacy against rotenone-induced oxidative damage in mice and isolated mitochondria. Methods MTC was synthesized by attaching the triphenylphosphonium cation (TPP) as a cationic carrier to the curcumin to assess its protective efficacy in rotenone-induced in-vitro and in-vivo toxicity in mice. Results In-vitro treatment of rotenone in isolated mitochondria caused a significant increase in lipid peroxidation (2.74 fold, 3.62 fold), protein carbonyl contents (2.62 fold, 1.81 fold), and decrease in levels of reduced glutathione (2.02 fold, 1.70 fold) as compared to control. Pre-treatment of curcumin and MTC along with rotenone in the isolated mitochondria significantly reduce the oxidative stress as compared to those treated with rotenone alone. Rotenone treatment in mice significantly increased lipid peroxidation (2.02 fold) and decreased the levels of reduced glutathione (2.99 fold), superoxide dismutase (2.09 fold) and catalase (3.60 fold) in the liver as compared to controls. Co-treatment of curcumin and MTC along with rotenone significantly reduced lipid peroxidation (1.26 fold, 1.76 fold) and increased the levels of reduced glutathione (1.60 fold, 2.43 fold), superoxide dismutase (1.45 fold, 1.99 fold) and catalase (2.32 fold, 2.90 fold) as compared to those treated with rotenone alone. Conclusion The results of the present study indicate that the protective efficacy of MTC against rotenone-induced oxidative damage was more promising than curcumin in both in-vitro and in-vivo system which indicates the enhanced bioavailability of MTC. Effect of mitochondrial targeted delivery of TPP-curcumin in rotenone-induced toxicity.

Oxidative stress is associated with mitochondrial impairments. Supplying mitochondria with potent antioxidants can reduce oxidative stress—induced mitochondrial impairment. Gallic acid can be used to reduce oxidative burden in mitochondria. In order to increase the bioavailability of gallic acid inside the mitochondria we synthesized mitochondrially targeted gallic acid and explored its preventive effects against sodium nitroprusside induced oxidative stress in isolated mitochondria. Our observations revealed an increase in oxidative stress,decrease in reduced glutathione in mitochondria and increase in the mitochondrial permeability pore transition due to sodium nitroprusside treatment. Pre—treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference. Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid. We conclude that mitochondrially targeted gallic acid can be used for preventing mitochondrial impairment caused by oxidative stress.