Toxin-derived peptides: An unconventional approach to alleviating cerebral stroke burden and neurobehavioral impairments.

Cerebral stroke is a pressing global health concern, ranking as the second leading cause of mortality and resulting in persistent neurobehavioral impairments. Cerebral strokes, triggered by various embolic events, initiate complex signaling pathways involving neuroexcitotoxicity, ionic imbalances, inflammation, oxidative stress, acidosis, and mitochondrial dysfunction, leading to programmed cell death. Currently, the FDA has approved tissue plasminogen activator as a relatively benign intervention for cerebral stroke, leaving a significant treatment gap. However, a promising avenue has emerged from Earth's toxic creatures. Animal venoms harbor bioactive molecules, particularly neuropeptides, with potential in innovative healthcare applications. These venomous components, affecting ion channels, receptors, and transporters, encompass neurochemicals, amino acids, and peptides, making them prime candidates for treating cerebral ischemia and neurological disorders. This review explores the composition, applications, and significance of toxin-derived peptides as viable therapeutic agents. It also investigates diverse toxins from select venomous creatures, with the primary objective of shedding light on current stroke treatments and paving the way for pioneering therapeutic strategies capable of addressing neurobehavioral deficits.

GLP-1/Sigma/RAGE receptors: An evolving picture of Alzheimer's disease pathology and treatment.

According to the facts and figures 2023stated that 6.7 million Americans over the age of 65 have Alzheimer's disease (AD). The scenario of AD has reached up to the maximum, of 4.1 million individuals, 2/3rd are female patients, and approximately 1 in 9 adults over the age of 65 have dementia with AD dementia. The fact that there are now no viable treatments for AD indicates that the underlying disease mechanisms are not fully understood. The progressive neurodegenerative disease, AD is characterized by amyloid plaques and neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau protein and senile plaques (SPs), which are brought on by the buildup of amyloid beta (Aß). Numerous attempts have been made to produce compounds that interfere with these characteristics because of significant research efforts into the primary pathogenic hallmark of this disorder. Here, we summarize several research that highlights interesting therapy strategies and the neuroprotective effects of GLP-1, Sigma, and, AGE-RAGE receptors in pre-clinical and clinical AD models.

Protective effect of L-ascorbic acid on nickel induced pulmonary nitrosative stress in male albino rats.

Nickel sulfate stimulates inducible nitric oxide synthase (i-NOS) and increases serum nitric oxide concentration by overproduction of reactive nitrogen species due to nitrosative stress. The present study was undertaken to assess possible protective role of L-ascorbic acid as an antioxidant against nickel induced pulmonary nitrosative stress in male albino rats. We studied the effect of the simultaneous treatment with L-ascorbic acid (50 mg/100 g b. wt.; orally) and nickel sulfate (2.0 mg/100 g b. wt.; i.p.) on nitric oxide synthesis by quantitative evaluation of serum i-NOS activities, serum and lung nitric oxide, L-ascorbic acid and protein concentrations of Wistar strain male albino rats. We have further studied histopathological changes in lung tissue after nickel sulfate treatment along with simultaneous exposure of L-ascorbic acid. Nickel sulfate treatment significantly increased the serum i-NOS activity, serum and pulmonary nitric oxide concentration and decreased body weight, pulmonary somatic index, serum and lung L-ascorbic acid and protein concentration as compared to their respective controls. Histopathological changes induced by nickel sulfate showed loss of normal alveolar architecture, inflammation of bronchioles, infiltration of inflammatory cells and patchy congestion of alveolar blood vessels. The simultaneous administration of L-ascorbic acid and nickel sulfate significantly improved all the above biochemical parameters along with histopathology of lung tissues of rats receiving nickel sulfate alone. The study clearly showed a protective role of L-ascorbic acid against nickel induced nitrosative stress in lung tissues.

α-Tocopherol ameliorates nickel induced testicular oxidative and nitrosative stress in albino rats.

BACKGROUND: Heavy metals generate free radicals and induce oxidative and nitrosative stress with depletion of antioxidants. In this study, we have evaluated the beneficial effects of α-tocopherol against nickel sulfate exposed testicular dysfunction. METHODS: We studied the effect of supplementation of α-tocopherol (10 mg/100 g body weight, i.m.) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced testicular oxidative and nitrosative stress in Wister strain male albino rats. Serum and testicular nitric oxide, L-ascorbic acid and serum α-tocopherol concentrations were evaluated. We also evaluated sperm count, motility and histopathology of testes. RESULTS: Nickel treated rats showed significantly decreased body weight, testicular somatic index, sperm count, sperm motility, serum and testicular L-ascorbic acid concentration and serum α-tocopherol level as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol produced a remarkable improvement of all the above parameters when compared with treatment with nickel alone. Nickel treated rats also had significantly increased serum and testicular nitric oxide concentrations as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol significantly decreased nitric oxide concentrations in both serum and testes, respectively, as compared to nickel treatment alone. Histopathology of the testes revealed tortuous seminiferous tubules, loss of spermatogenesis process (>75%), congestion and necrosis in nickel sulfate treated rats, whereas rats simultaneously treated with nickel sulfate and α-tocopherol had almost normal seminiferous tubules and near normal spermatogenesis as compared to nickel alone treated rats. CONCLUSIONS: Nickel sulfate treatment causes testicular oxidative and nitrosative stress in albino rats, but simultaneous supplementation of α-tocopherol was found to be beneficial in combating against such stresses.

A modified simple method for determination of serum α-tocopherol (vitamin E).

BACKGROUND: Vitamin E is one of the important antioxidants linked to regulate various diseases, such as atherosclerosis, hypertension, and male infertility. A relatively simple and economic biochemical modified method has been developed to determine serum α-tocopherol concentration. METHODS: The current modified method is based on previous Baker and Frank method and the method of Martinek by using 2,2'-bipyridyl, ferric chloride, and xylene. The complex of ferrous ions generated in this reaction with 2,2'-bipyridyl is determined by using a plain enzyme-linked immunosorbent assay microplate (non-antibody coated) at 492 nm. RESULTS: The standard curve of this new modified method shows a linearity with correlation r=0.997 (concentration vs. absorbance). The absorbance of this color complex is directly proportional to the α-tocopherol concentration. The sensitivity of this new modified method has been compared and correlated with Baker and Frank method by using 15 human samples (r=0.99, p<0.0001). CONCLUSIONS: This simple and economic method may be routinely used to analyze α-tocopherol concentration in serum.