IMPACT OF OXIDATIVE STRESS IN THE PATHOGENESIS OF CERVICAL CANCER THERAPEUTIC APPROCHES

Cervical cancer (CC) is acknowledged as the most ubiquitous carcinoma among females along with the utmost prevalence in developing nations. The major cause of CC is HPV exposure, especially HPV16 and 18. Inflammation is linked to the carcinogenesis of CC in addition to HPV infection. Although the precise cause of CC is yet unknown, using oral contraceptives, being immunosuppressed, and smoking may enhance the risk of the disease. Oxidative stress (OS), in addition to HPV, is linked to cervical cancer. Across several clinical and preclinical research, the dysfunctional redox system and the impact of oxidative stress throughout the aetiology of CC have been examined. Redox homeostasis must therefore be maintained, which calls for both enzymatic and nonenzymatic redox regulators. In this study, we explored the therapeutic strategies used to preserve redox balance, lower cervical cancer mortality, and illustrate the contribution of oxidative stress in the aetiology of the disease

Effects of vitaiin c supplementation on the chronic phase of chagas iisease / Efeitos da suplementação de vitamina C na fase crônica da doença de Chagas

Introduction: In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain. Methods: Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle. Results: Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever. Conclusion: Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory. .

Introdução: Para verificar a eficácia da vitamina C em combater o insulto oxidativo causado pelo Trypanosoma cruzi durante a evolução da fase crônica da doença de Chagas, camundongos Swiss foram previamente infectados via intraperitoneal com 5.0 × 104 tripomastigotas da cepa QM1 de T. cruzi. Métodos: Camundongos foram suplementados com duas diferentes doses de vitamina C por 180 dias. Foram mensurados os níveis de peroxidação lipídica (indicado por substâncias reativas ao ácido tiobarbitúrico-TBARS), peróxido total, vitamina C, e glutationa reduzida no plasma e TBARS, peróxido total e vitamina C no miocárdio, e foi realizado o estudo histopatológico em coração, cólon e músculo esquelético. Resultados: Animais que receberam diariamente uma dosagem equivalente a 500 mg de vitamina C apresentaram aumento na produção de ROS e RNS no plasma e no miocárdio e maior grau de inflamação e necrose em músculo esquelético em comparação àqueles que receberam doses menores ou nenhuma vitamina C. Conclusão: Embora muitas pesquisas tenham mostrado o efeito antioxidante da vitamina C, nossos resultados mostraram que os animais que foram expostos a 500 mg de vitamina C apresentaram maior dano tecidual na fase crônica da doença de Chagas, provavelmente devido a ações paradoxais desta substância, onde nesta patologia, poderá agir como pró-oxidante ou pró-inflamatória. .

The protective effects of echinacoside on oxidative stress injury in vascular dementia rats / 中国药理学通报

Aim To investigate the protective effects of echinacoside ( ECH ) on oxidative stress injury in vascular dementia rats. Methods Vascular dementia model was duplicated by means of permanent ligation of bilateral common carotid artery at two times intervals for three days. Biochemical methods was used to detect the GSH, NO, GSH-Px, NOS in each group rat’ s cor-tex and hippocampus. The change of the tissue struc-ture in CA1 area of hippocampus in each group was ob-served and analyzed by microscope after HE staining. Results Compared with sham group, the content of GSH and activity of GSH-Px in the rats of the model group were decreased significantly ( P0. 05 ) . Conclusion ECH exerts protection on oxida-tive stress injury in vascular dementia rats.

Reactive Oxygen Species and Nitrogen Species Differentially Regulate Neuronal Excitability in Rat Spinal Substantia Gelatinosa Neurons

Reactive oxygen species (ROS) and nitrogen species (RNS) are implicated in cellular signaling processes and as a cause of oxidative stress. Recent studies indicate that ROS and RNS are important signaling molecules involved in nociceptive transmission. Xanthine oxidase (XO) system is a well-known system for superoxide anions (O2(.-)) generation, and sodium nitroprusside (SNP) is a representative nitric oxide (NO) donor. Patch clamp recording in spinal slices was used to investigate the role of O2(.-) and NO on substantia gelatinosa (SG) neuronal excitability. Application of xanthine and xanthine oxidase (X/XO) compound induced membrane depolarization. Low concentration SNP (10 microM) induced depolarization of the membrane, whereas high concentration SNP (1 mM) evoked membrane hyperpolarization. These responses were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger). Addition of thapsigargin to an external calcium free solution for blocking synaptic transmission, led to significantly decreased X/XO-induced responses. Additionally, X/XO and SNP-induced responses were unchanged in the presence of intracellular applied PBN, indicative of the involvement of presynaptic action. Inclusion of GDP-beta-S or suramin (G protein inhibitors) in the patch pipette decreased SNP-induced responses, whereas it failed to decrease X/XO-induced responses. Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) decreased the effects of SNP, suggesting that these responses were mediated by direct oxidation of channel protein, whereas X/XO-induced responses were unchanged. These data suggested that ROS and RNS play distinct roles in the regulation of the membrane excitability of SG neurons related to the pain transmission.

Lipid peroxidation and total antioxidant capacity in health and disease - Pathophysiology and markers: An overview.

Free radicals play a significant role in the pathogenesis of many chronic diseases such as diabetes mellitus, cancer, chronic renal failure etc. Oxidative stress is defined as “a disturbance in the balance between the antioxidants and pro-oxidants (OFR in particular) with increased levels of pro-oxidants leading to potential damage. The knowledge about pathophysiology of lipid peroxidation and the oxidative stress biomarkers will definitely help the researchers to plan for focused study for better management of oxidative stress induced diseases.

Sensitivity of Diagnostic Tests and Therapeutic Outcome in Ocular Myasthenia Gravis

PURPOSE: To compare the sensitivity of various diagnostic tests, and to assess the efficacy of therapy in the management of myasthenia gravis (MG). METHODS: Thirty-two patients with ocular findings with MG were examined by Stimulated Single Fiber Electromyograhy (SFEMG), Repetitive Nerve Stimulation (RNS) test, Edrophonium (Tensilon) test, anti-acethylcholine receptor antibody titer. We also studied retrospectively clinical characteristics and efficacy RESULTS: Mean age of patients was 32 years (range 1 to 63 years). Twenty (62.5%) were females and 12 (37.5%) were males. Mean duration of symptoms was 17 months (range 5 months to 10 years). Associated ocular findings were ptosis 31 eyes (97%), diplopia 20 eyes (63%), and ocular limitation 19 eyes (59%). The value of diagnostic sensitivity was 97% in SFEMG, 94% in tensilon test, 75% in RNS test, and 69% in anti-acetylcholine receptor antibody assay. Nine of 10 cases who were treated with thymectomy and pyridostigmine were markedly improved. Eight cases (25%) subsequently developed generalized type of myasthenia gravis. CONCLUSIONS: Ptosis and diplopia were most frequently associated with ocular myasthenia gravis. For diagnosis of ocular myasthenia gravis, SFEMG or tensilon test was the most sensitive test. Thymectomy combined with pyridostigmine bromide seemed to be an effective therapeutic modality.

Role of NO in Activation of NFkB by PM 2.5 in Lung Epithelial Cells / 결핵

BACKGROUND:The present study was performed to further improve our understanding of the molecular mechanisms involved in the activation of NFkB, a major transcriptional factor involved in the inflammatory response in the inflammatory response in the lung, by particulate matter in lung epithelial cells wit an aerodynamic diameter of less than 2.5 micro meter(PM2.5). METHODS: Immediate production of reactive oxygen species (ROS) and nitrogen species (RNS), with the PM2.5 induced expression of inducible nitric oxide synthase (iNOS), IkB degradatio and NFkB-dependent transcrptional activity, in A 549 cells, were monitored. Addition, we also examined the effect of the iNOS inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL), on the PM 2.5-induced NFkB activation in A 549 cells. RESULTS:The rapid degradation of IkB and the increase of transcriptional activity of the NFkB-dependent promotor were observed in A 549 cells exposed to PM2.5. The immediate production of ROS in response to PM2.5 in A 549 cells was not clearly detected, although immediate responses were observed in RAW 264.7 cells. A549 cells, cultured in the presence of PM2.5, produced an increase in NO, which was noticeably significant after 15 min of exposure with the expression of iNOS mRNA. The addition of L-NIL, an iNOS inhibitor, significantly inhibited the PM2.5-induced IkB degradation and the increase of the NFkB-dependent transcriptional activity. CONCLUSION: These results suggest that PM2.5 stimulates the immediate production of RNS, leading to the activation of NFkB in the pulmonary epithelium.

Role of NO in Activation of NFkB by PM 2.5 in Lung Epithelial Cells / 결핵

BACKGROUND:The present study was performed to further improve our understanding of the molecular mechanisms involved in the activation of NFkB, a major transcriptional factor involved in the inflammatory response in the inflammatory response in the lung, by particulate matter in lung epithelial cells wit an aerodynamic diameter of less than 2.5 micro meter(PM2.5). METHODS: Immediate production of reactive oxygen species (ROS) and nitrogen species (RNS), with the PM2.5 induced expression of inducible nitric oxide synthase (iNOS), IkB degradatio and NFkB-dependent transcrptional activity, in A 549 cells, were monitored. Addition, we also examined the effect of the iNOS inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL), on the PM 2.5-induced NFkB activation in A 549 cells. RESULTS:The rapid degradation of IkB and the increase of transcriptional activity of the NFkB-dependent promotor were observed in A 549 cells exposed to PM2.5. The immediate production of ROS in response to PM2.5 in A 549 cells was not clearly detected, although immediate responses were observed in RAW 264.7 cells. A549 cells, cultured in the presence of PM2.5, produced an increase in NO, which was noticeably significant after 15 min of exposure with the expression of iNOS mRNA. The addition of L-NIL, an iNOS inhibitor, significantly inhibited the PM2.5-induced IkB degradation and the increase of the NFkB-dependent transcriptional activity. CONCLUSION: These results suggest that PM2.5 stimulates the immediate production of RNS, leading to the activation of NFkB in the pulmonary epithelium.