Biomedicine & Aging Pathology最新文献

The kidney is an imperative intention of the toxicity of drugs, xenobiotics, and oxidative stress. The intend of the present investigation was to conclude nephro-protective efficiency over mercuric chloride (MgCl₂) induced oxidative stress and renal injury in rats. Mercuric chloride induced nephrotoxicity (1 mg kg bw; i.p.) as it induces noticeable and characteristic changes in proximal tubular cells in group II animals. These changes are conduit and accompanied by signs of renal dysfunctions. The levels of blood urea, serum creatinine, uric acid, and lipid peroxidation were elevated (P < 0.05) in heavy metal intoxicated group II animals. On the other hand there was a decline in the levels of serum protein, nucleic acids, enzymic and non-enzymic antioxidant enzymes in group II toxicity induced rats. In group III, rats administration of kaempferol (100 mg kg bw p.o.) brought back these elevated urinary constituents, lipid peroxidation (P < 0.05) and increase the levels of antioxidants and nucleic acids levels to near normal (P < 0.05) due to its therapeutic and scavenging properties. Histopathological results muscularly supports the nephro-protective activities of kaempferol by convalescing oxidative damage and morphological changes of kidneys induced by MgCl₂. Therefore, the present analysis evidently showed that kaempferol may be useful due to antioxidant possessions in fighting against free radical-induced oxidative stress and tissue injury resulted from mercuric chloride induced nephrotoxicity.

Human beings are constantly exposed to UV radiations emitted by sun. Prolonged exposure to UV radiations initiates a series of pathophysiological events that account for photodamage in skin. Photoaging is the major contributor of skin melanoma and risk is particularly seen higher in fair skin population, with approximately 80 to 90% of European and North American population prevalent to skin photoaging. Importantly, skin cancer due to sun exposure is the most leading type of cancer prevalent in New Zealand; with approximately 67,000 new cases diagnosed every year with skin cancer. In fact, photoaging-associated skin cancer accounts for more than 65,000 deaths worldwide every year. This current and impending burden of the affected individuals provokes the need for further insight into the biochemical changes that contribute to the pathogenesis of skin cancer due to UV radiations and future therapeutic interventions to prevent and treat the associated skin disorders. On exposure to UV radiation, there is the generation of reactive oxygen species, reactive nitrogen species and inflammatory mediators. It also increases DNA damage in the body. All these factors together lead to degradation of collagen, and finally results in formation of wrinkles and angiogenesis which are the major clinical manifestations of photoaging. Further, UV radiations cause decrease in Langerhans cell, melanocyte, keratinocytes, fibroblast, collagen, tissue inhibitor of matrix metalloproteinase, various endogenous antioxidants and increase in level of various cytokines. Therefore, by understanding the molecular mechanisms underlying photoaging, new therapeutic managements can be identified and discovered.

Matrix metalloproteinases (MMPs) are endopeptidases involved in many physiological and physical processes. They synthesize and secrete numerous cytokines, growth factors, hormone receptors and cell adhesion molecules. The use of metalloproteinase inhibitors has been surmised in the treatment of important diseases such as cancer, neurodegenerative and cardiovascular diseases and various types of inflammatory diseases. With regard to the eyes, metalloproteinases and their inhibitors are implicated in the pathogenesis of diseases such as diabetic retinopathy, primary open-angle glaucoma, pseudoexfoliative glaucoma, corneal neovascularization and ulcerations (viral and bacterial), superior limbic keratoconjunctivitis, and climatic droplet keratopathy (CDK); they are secreted by the cells of the trabecular meshwork and their secretion increases after trabeculectomy surgery. They also take part in causing damage in the case of dry eye disease, pterygium, choroidal neovascularization (CNV) and age-related macular degeneration (AMD).

Preconditioning/ischemic tolerance of brain refers to a natural adaptive response induced by sublethal insults to increase brain resistance after stroke. Molecular studies can contribute to clarify precise mechanism(s) of this neuroprotective phenomenon. In this study, we attempted to determine durability of neuroprotection exerted by normobaric hyperoxia (HO) and its effects on mGluRII expression. Rats were divided into five groups (hyperoxia-intact, hyperoxia-MCAO, room air-intact, room air-MCAO and room air-sham). Hyperoxia groups consist of four subgroups (2HO, 5HO, 10HO and 15HO). It means that respectively 2, 5, 10 or 15 days after pretreatment (exposure to 95% inspired O₂ for 4 h/day and 6 consecutive days) animals were subjected to MCAO surgery (hyperoxia-MCAO group) or that decapitated as intact (hyperoxia-intact). Room air groups were considered as control and exposed to 21% oxygen. MCAO groups after the time specified in each group were subjected to 60 minutes of right middle cerebral artery occlusion (MCAO). 24 hours after reperfusion, neurologic deficit score (NDS) and brain infarct volume (IV) were evaluated in MCAO-operated groups. Sham operated and intact groups were used to assess expression of mGluR2/3 and glutathione (GSH) levels of core, penumbra and subcortex regions. Preconditioning with HO transiently decreased NDS and IV, and increased expression of mGluR2/3 in core, penumbra, and subcortex. These effects of hyperoxia disappeared gradually during15 days after pretreatment. Although additional studies will be required to further elucidate precise mechanism(s) in ischemic tolerance, it seems that likely part of protective effect of intermittent HO is associated with upregulation of mGluR2/3.

Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestation. It causes a hyperdynamic circulatory state because of a marked reduction in peripheral vascular resistance and an increased total blood volume and heart rate. We studied the changes in the heart structure of hyperthyroid rat at the post-pubertal stage, in addition to the role of folic acid in treatment. Thirty male Wistar rats were equally divided into six groups; the first and second groups were the control and folic acid groups respectively while the third group was the hyperthyroid rat group; the fourth and fifth groups were co- and post-treated hyperthyroid rat with folic acid respectively and the sixth group was self-treated hyperthyroid rat group. Serum T₃ andT₄ levels were significantly increased while TSH levels were significantly depressed in rats receiving thyroxine indicating the induction of hyperthyroid state. Left ventricle section in the heart of hyperthyroid rats showed many abnormalities such as myocardial hyperatrophy, hydrophobic changes of myofibrillar structure with striations, and focal haemorrhage when compared with that in control. The PCNA label index in cardiac tissues was significantly increased in hyperthyroid rat (grade 4) and their levels were significantly decreased in co- and post-treated hyperthyroid rats with folic acid (grades 3 and 2 respectively) when compared with control (grade 0). Treatment of hyperthyroid rats with folic acid improves the histopathological alternation and the intensity of PCNA immunoreactive cells demonstrating the recovery of some injury. In conclusion, our results indicated that folic acid had ameliorative effect against cardiac hypertrophy induced by thyroxine and the best results were found in case of using the folic acid as an adjuvant therapy after returning to the euthyroid state.

Phoenix dactylifera (PD) has been claimed for its neuroprotective potential in the traditional system of medicine but has not yet been scientifically documented. Phytochemical reports of Phoenix dactylifera fruits have demonstrated the presence of polyphenols and flavonoids, which have already been documented to play major role in neuroprotection against various experimental models of cerebral ischemia/reperfusion. In the present study, we have investigated the neuroprotective as well as antioxidant properties of methanolic extract of Phoenix dactylifera fruits (MEPD) at 30, 100, 300 mg/kg p.o against global cerebral ischemia-induced oxidative stress and neuronal death. The global cerebral ischemia was induced by occlusion of bilateral common carotid arteries for 5 min followed by 24 h of reperfusion. Varied biochemical/enzymatic alterations, produced subsequent to the application bilateral common carotid artery occlusion (BCCAO) followed by reperfusion viz. increase in lipid peroxidation and decrease in glutathione, glutathione reductase, catalase, glutathione-S-transferase, glutathione peroxidase and superoxide dismutase, were markedly reversed and restored to near normal levels in the groups pre-treated with 15 days. The pretreatment also reversed the histopathological changes induced by global cerebral ischemia in CA1 hippocampal region. The protective action, exhibited by MEPD against global cerebral induced brain injury, suggests its therapeutic potential in cerebrovascular diseases (CVD) including stroke. These findings are important because the present treatment strategies for CVD are far from adequate and PD with wide usage is known to be a safe natural product.

The objective of this study was to investigate effect of antidiabetic drug sitagliptin against diabetic retinopathy in wistar rats (150–180 gm). A non-diabetic group of animals received normal saline (group 1). Streptozotocin (65 mg/kg, i.p.) was administered in rats. After 15 days, rats that showed serum glucose above 200 mg/dL (diabetic) were randomly divided into following groups: group 2 (diabetic control), group 3 (sitagliptin 10 mg/kg), group 4 (sitagliptin 20 mg/kg), group 5 (sitagliptin 40 mg/kg). Serum glucose was determined periodically over a period of 90 days. Body weight and food intake of each rat was recorded during the study. Opthalmoscopic examination of the lens (slit microscopy) and retina (fundoscopy) was carried out every 7 days. Cataracted lens after the 60th day obscured the view of the retina and hence retinal damage was recorded till day 60 only. Lenticular opacities were scored under five categories (clear, stage 1, 2, 3 and 4 with stage 4 exhibiting maximum damage to the eye). On completion of 90 days, blood sugar and glycated hemoglobin was determined. Animals were then euthanized, eyes dissected and the advanced glycation end product (AGE) content of the lens was determined. Histopathology of the eye and pancreas was carried out. Animals of group 2 showed hyperglycemia, elevated glycated hemoglobin, cataract and retinal damage. Histopathology showed necrotic changes in lens. Sitagliptin showed dose dependent decrease in serum glucose, glycated hemoglobin, cataract development and retinal damage. It is concluded that, sitagliptin 40 mg/kg prolonged but not prevented the development of cataract and retinopathy in diabetic rats. Sitagliptin is effective as an ancillary drug for prolonging onset of diabetic retinopathy.

Ferulic acid (FA) is a phenolic phytonutrient, which possesses strong anticancer effect. However, its prominent application in cancer is limited due to poor bioavailability at the tumor site. Paclitaxel (PTX) is a semi synthetic drug which is used for cancer treatment. The aim of the study was to investigate the multidrug resistance of FA and PTX. It was noticed that anticancer potential of FA + PTX was greater than that of FA and PTX treatment alone. Further, FA + PTX exhibits increased TBARS, Catalase and SOD, altered GSH and GPx in NCI-H460 cells when compared to bulk FA and PTX treatment alone. Our results indicate that FA + PTX demonstrated increased anticancer property in cancer cells than FA and PTX treatment alone.