Natural and synthetic drugs and formulations for intravaginal HPV clearance.

BACKGROUND: Except for a few preventative Human Papillomavirus (HPV) vaccines, there is currently no cure for HPV infection. There are a number of cutting-edge strategies and potent medications or herbal formulations that can be applied topically for early clearance of HPV infection before HPV DNA gets integrated into host cell genome. This is facilitated due to cervical cancer having distinct and well-recognized long precancerous stages. OBJECTIVES: This review aims to outline every possible medication and formulation, both natural and synthetic, that can be applied topically as intravaginal application to help remove HPV infection at an early precancerous stage. RESULTS: Several anti-HPV/HPV clearance compounds and formulations for high-grade lesions are undergoing clinical trials. However, the majority of compounds are still in the early stages of development and require additional research to become viable HPV clearance candidates. Synthetic drugs may be more promising because they may have a more targeted effect; however, they may also have significant adverse effects. On the other hand, natural medications are safer to use. They are less specific, but have minimal to no adverse effects. CONCLUSIONS: This article may serve as a valuable resource of information for managing and preventing precancerous carcinogenic HPV infections. Research could be directed toward developing candidate drugs to make evidence-based decisions about advancing them to clinical trials and, eventually, to the market for potential use in the prevention and control of cervical cancer, which is almost always preventable or even curable if detected early.

Hippocampal glutathione depletion with enhanced iron level in patients with mild cognitive impairment and Alzheimer's disease compared with healthy elderly participants.

Oxidative stress has been implicated in Alzheimer's disease, and it is potentially driven by the depletion of primary antioxidant, glutathione, as well as elevation of the pro-oxidant, iron. Present study evaluates glutathione level by magnetic resonance spectroscopy, iron deposition by quantitative susceptibility mapping in left hippocampus, as well as the neuropsychological scores of healthy old participants (N = 25), mild cognitive impairment (N = 16) and Alzheimer's disease patients (N = 31). Glutathione was found to be significantly depleted in mild cognitive impaired (P < 0.05) and Alzheimer's disease patients (P < 0.001) as compared with healthy old participants. A significant higher level of iron was observed in left hippocampus region for Alzheimer's disease patients as compared with healthy old (P < 0.05) and mild cognitive impairment (P < 0.05). Multivariate receiver-operating curve analysis for combined glutathione and iron in left hippocampus region provided diagnostic accuracy of 82.1%, with 81.8% sensitivity and 82.4% specificity for diagnosing Alzheimer's disease patients from healthy old participants. We conclude that tandem glutathione and iron provides novel avenue to investigate further research in Alzheimer's disease.

Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders.

Glutathione (GSH) is an important antioxidant found abundantly and synthesized intracellularly in the cytosol in a tightly regulated fashion. It has diverse physiological functions, including protection against reactive oxygen species and nitrogen species, antioxidant defense as well as maintenance of cellular thiol status. The human brain due to the high oxygen consumption is extremely susceptible to the generation of reactive oxygen species. GSH plays a paramount role in brain antioxidant defense, maintaining redox homeostasis. The depletion of brain GSH has also been observed from both autopsies as well as in vivo MRS studies with aging and varied neurological disorders (Alzheimer's disease, Parkinson's disease, etc.). Therefore, GSH enrichment using supplementation is a promising avenue in the therapeutic development for these neurological disorders. This review will enrich the information on the importance of GSH synthesis, metabolism, functions, compartmentation and inter-organ transport, structural conformations and its quantitation via different techniques. The transportation of GSH in the brain via different interventional routes and its potential role in the development of therapeutic strategies for various brain disorders is also addressed. Very recent study found significant improvement of behavioral deficits including cognitive decline, depressive-like behaviors, in APP (NL-G-F/NL-G-FG-) mice due to oral GSH administration. This animal model study put an emergent need to complete GSH supplementation trial in MCI and AD patients for cognitive improvement as proposed earlier.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain.

OBJECTIVE: The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats. METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay. RESULTS: Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain. CONCLUSION: The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.

Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p<0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p<0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p<0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p<0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure.

Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity microwave radiation.

The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10(-4) W/kg; group III: exposed to 1800 MHz, SAR 5.835 × 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10(-4) W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.

Effect of Low-Intensity Microwave Radiation on Monoamine Neurotransmitters and Their Key Regulating Enzymes in Rat Brain.

The increasing use of wireless communication devices has raised major concerns towards deleterious effects of microwave radiation on human health. The aim of the study was to demonstrate the effect of low-intensity microwave radiation on levels of monoamine neurotransmitters and gene expression of their key regulating enzymes in brain of Fischer rats. Animals were exposed to 900 MHz and 1800 MHz microwave radiation for 30 days (2 h/day, 5 days/week) with respective specific absorption rates as 5.953 × 10(-4) and 5.835 × 10(-4) W/kg. The levels of monoamine neurotransmitters viz. dopamine (DA), norepinephrine (NE), epinephrine (E) and serotonin (5-HT) were detected using LC-MS/MS in hippocampus of all experimental animals. In addition, mRNA expression of key regulating enzymes for these neurotransmitters viz. tyrosine hydroxylase (TH) (for DA, NE and E) and tryptophan hydroxylase (TPH1 and TPH2) (for serotonin) was also estimated. Results showed significant reduction in levels of DA, NE, E and 5-HT in hippocampus of microwave-exposed animals in comparison with sham-exposed (control) animals. In addition, significant downregulation in mRNA expression of TH, TPH1 and TPH2 was also observed in microwave-exposed animals (p < 0.05). In conclusion, the results indicate that low-intensity microwave radiation may cause learning and memory disturbances by altering levels of brain monoamine neurotransmitters at mRNA and protein levels.

Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats.

BACKGROUND: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. OBJECTIVE: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. MATERIALS AND METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10(-4) W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10(-4) W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10(-4) W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. RESULTS: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. CONCLUSION: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue.

Effect of low level microwave radiation exposure on cognitive function and oxidative stress in rats.

Use of wireless communicating devices is increasing at an exponential rate in present time and is raising serious concerns about possible adverse effects of microwave (MW) radiation emitted from these devices on human health. The present study aimed to evaluate the effects of 900 MHz MW radiation exposure on cognitive function and oxidative stress in blood of Fischer rats. Animals were divided into two groups (6 animals/group): Group I (MW-exposed) and Group II (Sham-exposed). Animals were subjected to MW exposure (Frequency 900 MHz; specific absorption rate 8.4738 x 10(-5) W/kg) in Gigahertz transverse electromagnetic cell (GTEM) for 30 days (2 h/day, 5 days/week). Subsequently, cognitive function and oxidative stress parameters were examined for each group. Results showed significant impairment in cognitive function and increase in oxidative stress, as evidenced by the increase in levels of MDA (a marker of lipid peroxidation) and protein carbonyl (a marker of protein oxidation) and unaltered GSH content in blood. Thus, the study demonstrated that low level MW radiation had significant effect on cognitive function and was also capable of leading to oxidative stress.

Microwave radiation induced oxidative stress, cognitive impairment and inflammation in brain of Fischer rats.

Public concerns over possible adverse effects of microwave radiation emitted by mobile phones on health are increasing. To evaluate the intensity of oxidative stress, cognitive impairment and inflammation in brain of Fischer rats exposed to microwave radiation, male Fischer-344 rats were exposed to 900 MHz microwave radiation (SAR = 5.953 x 10(-4) W/kg) and 1800 MHz microwave radiation (SAR = 5.835 x 10(-4) W/kg) for 30 days (2 h/day). Significant impairment in cognitive function and induction of oxidative stress in brain tissues of microwave exposed rats were observed in comparison with sham exposed groups. Further, significant increase in level of cytokines (IL-6 and TNF-alpha) was also observed following microwave exposure. Results of the present study indicated that increased oxidative stress due to microwave exposure may contribute to cognitive impairment and inflammation in brain.