No abstract

The current study aimed to demonstrate the potentially adverse effects of adrenaline, an endogenous stressor, on the melatonergic system, oxidative status, antioxidative responses and inflammatory markers in different parts of gastrointestinal tract of Wistar rat. These included stomach, duodenum and colon and they were incubated with different concentrations (2.5, 5.0 and 10.0 µg/mL) of adrenaline for 1h, respectively. The levels of melatonin, gene expressions of arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1 (MT1) as well as other stress-induced parameters including NF-kB expression, levels of cAMP, calcium, malondialdehyde, protein carbonyl content, reduced glutathione, nitrate, superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase, tumour necrosis factor-α, IL-1β, IL6 and IL10 were systemically measured in these tissues. An adrenaline dose-dependent decrease in level of melatonin, AANAT, MT1 and NF-kB in these tissues were observed. In contrast, the profound increases in the levels of cAMP, calcium and all oxidative stress markers, inflammatory cytokines (except IL10), and activities of antioxidant enzymes (except superoxide dismutase) were observed after adrenaline treatment. A maximum effect was found in tissues treated with 5 µg/mL of adrenaline. The Correlation studies between melatonin level and other parameters (any two at a time) indicated a potentially physiological interplay between adrenaline stress and melatonin tissue levels. Collectively, the results provided the novel data on the adverse effects of adrenaline on the endogenous melatonergic system, antioxidant and inflammatory responses in the gastrointestinal tissues of rats.

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The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress.  In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

No abstract

Reduction of mitochondrial oxidative stress-mediated diseases is an important pharmaceutical objective in recent biomedical research. In this context, a series of novel pyrrolobenzoxazines (PyBs) framework with enormous diversity (compounds 5a–w) was synthesized by employing a low-temperature greener pathway, and antioxidant property of the synthesized compounds was successfully demonstrated on preclinical model goat heart mitochondria, in vitro. Copper–ascorbate (Cu–As) was utilized as an oxidative stress generator. Out of screened PyBs, the compound possessing −OH and −OMe groups on benzene nucleus along with pyrrolobenzoxazine core moiety (compound 5w) displayed magnificent antioxidant property with a minimum effective dose of 66 μM during the biochemical assessment. The ameliorative effect of synthesized pyrrolobenzoxazine moiety on levels of biomarkers of oxidative stress, antioxidant enzyme, activities of Krebs cycle and respiratory chain enzymes, mitochondrial morphology, and Ca2+ permeability of mitochondrial membrane was investigated in the presence of Cu–As. Furthermore, the binding mode of Cu–As by compound 5w was explored successfully using isothermal titration calorimetry (ITC) analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medicines to treat numerous pathophysiological conditions clinically. However, growing evidence indicates the adverse effects of NSAIDs on the different vital organs, among which gastrointestinal (GI) tract seems to be the utmost target in most of the cases. NSAIDs promote over production of harmful reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the gastric mucosa. These toxic species cause microvascular damage, increasing intestinal permeability, leading to the development of gastric lesions including ulcerations. Several strategies have been proposed to reduce the side effects of NSAIDs on the GI tissue, but most of them have failed to achieve this goal. Identification of an appropriate therapeutic strategy is urgently required. It is our opinion that this novel strategy to target GI damage induced by NSAID should include both anti-inflammatory and antioxidant properties. Under such a circumstance melatonin probably is the best choice for this purpose. Melatonin is a broad spectrum antioxidant and anti-inflammatory molecule. Numerous studies have reported the protective role of melatonin against gastric tissue damages caused by NSAIDs in animals or clinically. However, the underlying molecular mechanisms are not fully clarified. Thus, the present review attempts to gather the available information on this topic to provide a clear understanding on the exact scenario of this aspect.

Cadmium (Cd) is a notorious environmental pollutant known for its wide range of toxicities to organisms. Thus, the present study is designed to examine whether melatonin, a potent antioxidant, protects against Cd-induced oxidative damage in the heart, liver and kidney of rats. Cd treatment at a dose of 0.44 mg/kg for 15 days caused severe damage in all these organs. These included significantly increased activities of SGPT, SGOT, lactate dehydrogenase- 1 and 5 and ALP and levels of total lactate, creatinine, lipid peroxidation, protein carbonyl content and reduced glutathione while the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase along with mitochondrial pyruvate dehydrogenase, isocitrate dehydrogenase, α-keto glutarate dehydrogenase, succinate dehydrogenase, NADH-cytochrome-c-oxidoreductase and cytochrome-c-oxidase were significantly reduced by Cd. However, if melatonin was given orally 30 min before Cd injection, all these alterations induced by Cd were significantly preserved by melatonin. Histological observations also demonstrated that Cd exposure caused cellular lesions, promoting necrotic or apoptotic changes. Notably, all these changes were significantly protected by melatonin. The results suggest that melatonin is a beneficial molecule to ameliorate Cd-induced oxidative damage in the heart, liver and kidney tissues of rats with its powerful antioxidant capacity, heavy metal chelating activity and competition of binding sites with Cd to the GSH and catalase.