Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use in consumer products and medicines; also, the potential effects on reproduction and fertility are relevant for this risk evaluation. In the present study, we examined the effects of intravenously injected titanium dioxide nanoparticles (TiO2-NPs; 21 nm), with special emphasis on reproductive system. Antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase showed a significant decrease, while significant increase in lipid peroxidase was observed. Our results confirmed the bioaccumulation of TiO2-NPs in testicular cells. In TiO2-NPs-treated animals, various functional and pathological disorders, such as reduced sperm count, increase in caspase-3 (a biomarker of apoptosis), creatine kinase activity, DNA damage, and cell apoptosis were observed. Moreover, the testosterone activity was decreased significantly in a dose-dependent manner in the animals treated with TiO2-NPs as compared with control group animals. It is concluded that TiO2-NPs induce oxidative stress, which produce cytotoxic and genotoxic changes in sperms which may affect the fertilizing potential of spermatozoa.
Microwave (MW) radiation produced by wireless telecommunications and a number of electrical devices used in household or in healthcare institutions may adversely affects the reproductive pattern. Present study aimed to investigate the protective effects of melatonin (is well known antioxidant that protects DNA, lipids and proteins from free radical damage) against oxidative stress-mediated testicular impairment due to long-term exposure of MWs. For this, 70-day-old male Wistar rats were divided into four groups (n = 6/group): Sham exposed, Melatonin (Mel) treated (2 mg/kg), 2.45 GHz MWs exposed and MWs + Mel treated. Exposure took place in Plexiglas cages for 2 h a day for 45 days where, power density (0.21 mW/cm(2)) and specific absorption rate (SAR 0.14 W/Kg) were estimated. After the completion of exposure period, rats were sacrificed and various stress related parameters, that is LDH-X (lactate dehydrogenase isoenzyme) activity, xanthine oxidase (XO), ROS (reactive oxygen species), protein carbonyl content, DNA damage and MDA (malondialdehyde) were performed. Result shows that melatonin prevent oxidative damage biochemically by significant increase (p < 0.001) in the levels of testicular LDH-X, decreased (p < 0.001) levels of MDA and ROS in testis (p < 0.01). Meanwhile, it reversed the effects of MWs on XO, protein carbonyl content, sperm count, testosterone level and DNA fragmentation in testicular cells. These results concluded that the melatonin has strong antioxidative potential against MW induced oxidative stress mediated DNA damage in testicular cells.
2,4-Thiazolidinedione (2,4-TZD), commonly known as glitazone, is a ubiquitous heterocyclic pharmacophore possessing a plethora of pharmacological activities and offering a vast opportunity for structural modification. The diverse range of biological activities endowed with a novel mode of action, low cost, and easy synthesis has attracted the attention of medicinal chemists. Several researchers have integrated the TZD core with different structural fragments to develop a wide range of lead molecules against various clinical disorders. The most common sites for structural modifications at the 2,4-TZD nucleus are the N-3 and the active methylene at C-5. The review covers the recent development of TZD derivatives such as antimicrobial, anticancer, and antidiabetic agents. Various 2,4-TZD based agents or drugs, which are either under clinical development or in the market, are discussed in the study. Different synthetic methodologies for synthesizing the 2,4-TZD core are also included in the manuscript.The importance of various substitutions at N-3 and C-5 and the mechanisms of action and structure-activity relationships are also discussed. We hope this study will serve as a valuable tool for the scientific community engaged in the structural exploitation of the 2,4-TZD core for developing novel drug m\olecules for life-threatening ailments.
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