Molecular Mechanisms of Oxidative Stress in Acute Kidney Injury: Targeting the Loci by Resveratrol.

Reactive oxygen species are a group of cellular molecules that stand as double-edged swords, their good and bad being discriminated by a precise balance. Several metabolic reactions in the biological system generate these molecules that interact with cellular atoms to regulate functions ranging from cell homeostasis to cell death. A prooxidative state of the cell concomitant with decreased clearance of such molecules leads to oxidative stress, which contributes as a prime pathophysiological mechanism in various diseases including renal disorders, such as acute kidney injury. However, targeting the generation of oxidative stress in renal disorders by an antioxidant, resveratrol, is gaining considerable therapeutic importance and is known to improve the condition in preclinical studies. This review aims to discuss molecular mechanisms of oxidative stress in acute kidney injury and its amelioration by resveratrol. The major sources of data were PubMed and Google Scholar, with studies from the last five years primarily included, with significant earlier data also considered. Mitochondrial dysfunction, various enzymatic reactions, and protein misfolding are the major sources of reactive oxygen species in acute kidney injury, and interrupting these loci of generation or intersection with other cellular components by resveratrol can mitigate the severity of the condition.

Nephroprotective Effect of Diosmin against Cisplatin-Induced Kidney Damage by Modulating IL-1ß, IL-6, TNFα and Renal Oxidative Damage.

Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1ß, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.

Potential of paracetamol for reproductive disruption: molecular interaction, dynamics, and MM-PBSA based in-silico assessment.

Paracetamol is generally recommended for pain and fever. However, as per experimental and epidemiological data, widespread and irrational or long-term use of paracetamol may be harmful to human endocrine homeostasis, especially during pregnancy. Some researchers suggest that prenatal exposure to paracetamol might alter fetal development and also enhance the risk of reproductive disorders. An imbalance in the levels of these hormones may play a significant role in the emergence of various diseases, including infertility. Therefore, in this study, the interaction mechanism of paracetamol with reproductive hormone receptors was investigated by molecular docking, molecular dynamics (MD) simulations, and Poisson-Boltzmann surface area (MM-PBSA) for assessing paracetamol's potency to disrupt reproductive hormones. The results indicate that paracetamol has the ability to interact with reproductive hormone receptors (estrogen 1XP9; 1QKM with binding energy of -5.61 kcal/mol; -5.77 kcal/mol; androgen 5CJ6 - 5.63 kcal/mol; and progesterone 4OAR -5.60 kcal/mol) by hydrogen bonds as well as hydrophobic and van der Waals interactions to maintain its stability. In addition, the results of the MD simulations and MM-PBSA confirm that paracetamol and reproductive receptor complexes are stable. This research provides a molecular and atomic level understanding of how paracetamols disrupt reproductive hormone synthesis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), Radius of Gyration and hydrogen bonding exhibited that paracetamol mimic at various attribute to bisphenol and native ligand.

Inflammation and Alzheimer's Disease: Mechanisms and Therapeutic Implications by Natural Products.

Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.

Screening of the GPX3 gene identifies the "T" allele of the SNP -861A/T as a risk for ischemic stroke in young Asian Indians.

BACKGROUND: Deficiency of plasma glutathione peroxidase (GPx-3) has been associated with platelet-dependent thrombosis. Single-nucleotide polymorphisms (SNPs) in the promoter region of GPX3 gene have been found associated with the risk for ischemic stroke in Caucasian populations. The aim of our present study was to evaluate the impact of genetic variations in the GPX3 gene and plasma GPx-3 antigen levels on ischemic stroke in young Asian Indians. METHODS: One hundred patients with ischemic stroke and 200 age- and sex-matched controls were studied. Genetic analysis for the study population was done by a combination of variant screening using single-stranded conformation polymorphism and final genotyping by polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reactions. Plasma GPx-3 antigen levels were evaluated using commercial kits. Data were analyzed using genetic analysis software and statistical tools. RESULTS: Significantly higher GPx-3 levels were observed in controls compared with patients (controls 26.37 ± 3.66 µg/mL and patients 22.83 ± 4.57 µg/mL, P < .001). Only the SNP -861A/T was found associated with stroke phenotype (P < .0001). The SNP -568T/C was observed to significantly influence plasma GPx-3 levels (P < .05). The haplotype carrying the risk "T" allele of SNP -861A/T was significantly over-represented in patients with stroke (P < .0001). CONCLUSIONS: The T allele of -861A/T is a risk allele for the ischemic stroke phenotype. The -861A/T and -568T/C SNPs may show a statistically significant association with both plasma GPx-3 antigen levels and the stroke phenotype in a larger sample size.

Eclampsia-Associated Posterior Reversible Encephalopathy Syndrome (PRES) Complicated by Intracerebral Hemorrhage: A Case Report and Review of Management Strategies.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome that is being increasingly recognized due to the advancements in brain imaging, specifically MRI. This syndrome is characterized by symptoms including, but not limited to, headache, seizures, altered mental status, and vision loss. There are various underlying etiologies which lead to PRES occurrence; the etiology of focus in this report is preeclampsia and eclampsia. PRES is associated with the development of various types of intracerebral hemorrhage which can lead to detrimental and even fatal consequences in a patient. In our case, a 22-year-old female developed PRES within one week postpartum, which was complicated by parenchymal hemorrhage development in the fronto-parietal lobe. MRI findings were characteristic for PRES with multiple subcortical hyperintensities within the bilateral occipital lobe. The patient improved symptomatically after management with intravenous fluids, antihypertensives, antiepileptics, and antibiotics. This report aims to explore the association between preeclampsia/eclampsia (PE/E) and PRES and underscore the importance of prompt diagnosis and treatment, which can lead to recovery within a week and significantly reduce morbidity and mortality.

Hematotoxicity of Co-Administration of Bisphenol A and Acetaminophen in Rats and its Amelioration by Melatonin.

BACKGROUND: Hematotoxicity is an underexplored endpoint of toxicity in most of the chemical exposures. An adverse effect on the hematological system arising out of xenobiotic exposure causes impaired hemostasis and coagulation leading to disease. BPA and acetaminophen are widely used synthetic chemicals worldwide and both are known and have numerous toxic effects. Since both can be simultaneously exposed to humans over a period of time, we hypothesized that their exposure can cause hematotoxicity, which may be ameliorated by melatonin. OBJECTIVE: In the current study, we aimed to find the effect of single and co-treatment of bisphenol A and acetaminophen on the RBC and coagulation factors in rats, and amelioration of impairment by melatonin. METHODS: Oxidative stress in red blood cells, bleeding time, blood clotting time, prothrombin time, partial thromboplastin time, and fibrinogen levels were assessed as indicators of hematotoxicity with single and co-exposure to bisphenol A and acetaminophen in rats. The effect of melatonin as a hemato-protective agent was assessed in the co-exposure. RESULTS: An increase in RBC oxidative stress and decrease in bleeding time, blood clotting time, prothrombin time, and partial thromboplastin time along with an increase in fibrinogen levels were observed with bisphenol A and acetaminophen treatment, which were further aggravated with cotreatment of the two. Melatonin treatment, however, was seen to decrease the increase in oxidative stress and ameliorate the impairment in coagulation factors. CONCLUSION: Bisphenol A and acetaminophen cause an increase in the oxidative stress in the red blood cells, and cause a shift toward pro-coagulation, which is alleviated by treatment with melatonin.

Mitochondria: Emerging Consequential in Sickle Cell Disease.

Advanced mitochondrial multi-omics indicate a multi-facet involvement of mitochondria in the physiology of the cell, changing the perception of mitochondria from being just the energy-generating organelles to organelles that highly influence cell structure, function, signaling, and cell fate. This sets mitochondrial dysfunction in the centerstage of numerous acquired and genetic diseases. Sickle cell disease is also being increasingly associated with mitochondrial anomalies and the pathophysiology of sickle cell disease finds mitochondria at crucial intersections in the pathological cascade. Altered mitophagy, increased ROS, and mitochondrial DNA all contribute to the condition and its severity. Such mitochondrial aberrations lead to consequent mitochondrial retention in red blood cells in sickle cell diseases, increased oxidation in the cellular environment, inflammation, worsened vaso-occlusive crisis, etc. There are increasing studies indicating mitochondrial significance in sickle cell disease, consequently providing an opportunity to target it for improving the outcomes of treatment. Identification of the impaired mitochondrial attributes in sickle cell disease and their modulation by therapeutic interventions can impart a better management of the disease. This review aims to describe the mitochondria in the perspective of sicke cell disease so as to provide the reader an overview of the emerging mitochondrial stance in sickle cell disease.

The Future of Precision Medicine in the Cure of Alzheimer's Disease.

This decade has seen the beginning of ground-breaking conceptual shifts in the research of Alzheimer's disease (AD), which acknowledges risk elements and the evolving wide spectrum of complicated underlying pathophysiology among the range of diverse neurodegenerative diseases. Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach to precision medicine (PM), as is the case with several other diseases. This strategy will probably be based on the achievements made in more sophisticated research areas, including cancer. PM will require the direct integration of neurology, neuroscience, and psychiatry into a paradigm of the healthcare field that turns away from the isolated method. PM is biomarker-guided treatment at a systems level that incorporates findings of the thorough pathophysiology of neurodegenerative disorders as well as methodological developments. Comprehensive examination and categorization of interrelated and convergent disease processes, an explanation of the genomic and epigenetic drivers, a description of the spatial and temporal paths of natural history, biological markers, and risk markers, as well as aspects about the regulation, and the ethical, governmental, and sociocultural repercussions of findings at a subclinical level all require clarification and realistic execution. Advances toward a comprehensive systems-based approach to PM may finally usher in a new era of scientific and technical achievement that will help to end the complications of AD.

Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage.

Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1ß, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.

Mitochondrial oxidative damage by co-exposure to bisphenol A and acetaminophen in rat testes and its amelioration by melatonin.

OBJECTIVE: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. METHODS: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. RESULTS: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. CONCLUSION: Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

SARS-CoV-2 Infection: Modulator of Pulmonary Embolism Paradigm.

Pulmonary embolism (PE) is a life-threatening complication arising from venous thromboembolism with a difficult diagnosis and treatment and is often associated with increased mortality and morbidity. PE had a significantly low incidence prior to the COVID-19 epidemic. This condition saw a sharp surge during the COVID-19 pandemic, indicating an evident viral influence on PE's pathophysiology in COVID-19 patients. The hypercoagulable state induced by the viral load seems to be the major contributor, and the classical causative factors seem to play a lesser role. PE in COVID-19 infection has become a mammoth challenge since the diagnosis is quite challenging due to overlapping symptoms, lack of prior-known predisposing risk factors, limited resources, and viral transmittance risk. Numerous factors arising out of the viral load or treatment lead to an increased risk for PE in COVID-19 patients, besides the fact that certain unknown risk factors may also contribute to the incidence of PE in COVID-19 patients. The management of PE in COVID-19 infection mainly comprises thromboprophylaxis and anticoagulant therapy with mechanical ventilation, depending on the risk stratification of the patient, with a post-COVID-19 management that prevents recurrent PE and complications. This review aims to discuss various aspects of COVID-19-infection-associated PE and major differential aspects from non-COVID-19 PE.

Iron Deficiency Anemia as a Factor in Male Infertility: Awareness in Health College Students in the Jazan Region of Saudi Arabia.

Male contribution towards couple infertility is increasing but is less discussed. We aimed to assess the knowledge about iron deficiency anemia (IDA) as a contributor to male infertility in students at health colleges of Jazan University. A multicentric, cross-sectional survey included 910 participants and 768 participants qualified as per our inclusion criteria. The questions were categorized as: Model 1-knowledge about IDA-induced male infertility; Model 2-knowledge about IDA. The average knowledge of IDA causing male infertility is very low among students. The 18-20 years age group had a lesser score for either knowledge of IDA (M2; p-value = 0.047) or total (p-value < 0.0001) compared to the older group. In addition, female students were significantly more likely to be better in achieving higher total scores (p-value = 0.023) as well as M2 scores (p-value < 0.0001) when compared to the respective male category. On the other hand, males were significantly better in scoring for M1 (p-value = 0.004) compared to females. Awareness about iron deficiency anemia as a factor in male infertility may reduce the infertility burden, arising from a preventable factor, in the Jazan region.

Melatonin Ameliorates BPA Induced Oxidative Stress in Human Red Blood Cells: An In vitro Study.

BACKGROUND: Bisphenol A (BPA) is a xenobiotic that causes oxidative stress in various organs in living organisms. Blood cells are also an endpoint where BPA is known to cause oxidative stress. Blood cells, especially red blood cells (RBCs), are crucial for maintaining homeostasis and overall wellbeing of the organism. They are highly susceptible to oxidative stress induced by xenobiotics. However, there is limited data about the oxidative stress induced by BPA in blood, especially in red blood cells. This study was carried out to evaluate BPA induced oxidative stress in human RBCs in vitro and its amelioration by melatonin. OBJECTIVE: To find if melatonin exerts a protective effect on the oxidative stress induced by the BPA in human red blood cells in vitro. METHODS: The erythrocyte suspensions (2 ml) were divided into six groups and treated with 0, 50, 100, 150, 200, and 250 µg/ml of BPA. Another set of erythrocyte suspension with similar BPA treatment and 50 µM Melatonin per group was also set. Incubations lasted for 12 hrs in the dark. Lipid peroxidation, glutathione, glutathione reductase, catalase, and superoxide dismutase were measured as indicators of oxidative stress. RESULTS: BPA caused a significant increase in lipid peroxidation. A decrease in GSH levels was also observed. The activities of all the studied antioxidants also decreased with BPA treatment. Melatonin was seen to mitigate the oxidative stress induced by BPA. CONCLUSION: Treatment of red blood cells with BPA caused an increase in oxidative stress, while melatonin decreased the induced oxidative stress.

Diet: A Source of Endocrine Disruptors.

BACKGROUND: Food is indispensable for human life and determines the health and wellbeing of the consumer. As food is the source of energy for humans, it also emerges as one of the most important sources of exposure to deleterious chemicals both natural and synthetic. The food exposed chemicals cause a number of detrimental health effects in humans, with endocrine disruption being of serious concern amongst these effects. Such chemicals disrupting the health of endocrine system are known as endocrine-disrupting chemicals (EDCs). The food exposed EDCs need to be identified and classified to effectuate a cautious consumption of food by all and especially by vulnerable groups. AIM: The aim of the present review was to discuss food as a source of exposure to common endocrine disruptors in humans. This review presents the occurrence and levels of some of the critical endocrine disruptors exposed through frequently consumed diets. METHODS: The major source of data was PubMed, besides other relevant publications. The focus was laid on data from the last five years, however significant earlier data was also considered. CONCLUSION: The food as a source of endocrine disruptors to humans cannot be neglected. It is highly imperative for the consumer to recognize food as a source of EDCs and make informed choices in the consumption of food items.

Iron deficiency augments bisphenol A-induced oxidative stress in rats.

Bisphenol A (BPA), an estrogenic environmental contaminant is also known for oxidative stress-inducing effect. Malnutrition is recognized as a confounding factor in oxidative stress. However, little is known about effect of malnutrition on oxidative stress induced by BPA or other endocrine disrupting chemicals (EDCs). We studied effect of malnutrition (iron deficiency) in rats chronically exposed to low levels of BPA taking into consideration the oxidative stress and antioxidant status in liver, kidney and gonads. Iron deficiency significantly elevated level of lipid peroxidation in BPA-exposed rats. Similarly, decrease in reduced glutathione level was more significant in rats maintained on iron deficient diet compared to those maintained on normal diet. Iron deficiency also significantly modulated activities of vital antioxidant enzymes in all the tissues. Female rats showed more vulnerability than males to iron-deficiency modulated effects of BPA on the above parameters. This study demonstrated that malnutrition, especially iron deficiency, might act as a confounding factor in EDC-induced oxidative stress. However, more studies may be needed to confirm effect of nutritional factors on estrogenic activity of BPA or other EDCs.

Genotoxic and oxidative stress-inducing effects of deltamethrin in the erythrocytes of a freshwater biomarker fish species, Channa punctata Bloch.

Deltamethrin, an alpha-cyano class of pyrethroid insecticide is used in insect pest control and antimalaria programs in several countries including India. Although various toxic manifestations of deltamethrin are reported in mammals, its ecotoxicologic dimensions are not adequately researched in ecologically and commercially important fishes. In this study, we report genotoxic effect of deltamethrin in a biomarker fish Channa punctata (Bloch). Adult fish were exposed to three concentrations of technical grade deltamethrin (0.4, 0.8, and 1.2 microg/L) for 48 and 72 h. Ethyl methane sulfonate was used as a positive control. Fish were analyzed for induction of micronucleus (MN), nuclear abnormalities (NAs), and oxidative stress biomarkers in erythrocytes. Deltamethrin significantly induced MN and NAs accompanied by increased lipid peroxidation. Activity of antioxidant enzyme superoxide dismutase was significantly decreased but an increase was observed in reduced glutathione level after 72 h of exposure. The NAs in exposed fish included blebbed, lobed and notched nuclei, and binucleated erythrocytes. Our findings suggest that oxidative stress may, in part, be contributing to deltamethrin-induced genotoxic damage to erythrocytes. Although MN induction is a nonspecific biomarker, it may provide an indication of pollution load of deltamethrin in the affected fish population when used as part of suite of other biomarkers.

Evaluation of Immunization Coverage in the Rural Area of Peshawar, Khyber Pakhtunkhwa.

BACKGROUND: In children, the leading cause of morbidity and mortality is infectious disease. Immunization is one of the most cost-effective methods for child survival. The purpose of the survey is to assess access and coverage of immunizations in the rural areas of the District Peshawar, Khyber Pakhtunkhwa. METHODS: A cross­sectional study was conducted in a rural population area of District Peshawar from February 2016 to April 2016 using the WHO's 30 cluster sampling method for evaluation of immunization coverage. RESULTS: A total of 390 children aged 12-23 months were included in the study. It was found that 67.94% of the children were fully immunized against vaccine-preventable diseases. Thirty percent of the children were partially immunized; the percentage of unimmunized children was 2.06%. Immunization cards were issued to and available with 58.8% of the subjects. The most common cause of partial immunization was a lack of information regarding vaccinations (27%). Immunization against measles was found to be low (67%). Those using private facilities were more likely to be completely immunized as compared to government facilities. CONCLUSIONS: Immunization coverage in our survey was 68%. Sustained efforts are required to achieve universal coverage of immunization. Significant interventions are required, especially in areas that are more rural and less educated.

Topically applied vitamin E prevents massive cutaneous inflammatory and oxidative stress responses induced by double application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice.

Vitamin E (alpha-tocopherol) is a promising chemopreventive and pharmacologically safe agent, which can be exploited or tested against skin cancer. It is an established antioxidant with an ability to ameliorate the UV-induced skin damage and chemically induced inflammation in lungs. However, there are some conflicting reports about its role as a modulator of chemically induced promotion. We evaluated its efficacy in preventing the inflammatory and oxidative stress responses in a double 12-O-tetradecanoylphorbol-13-acetate (TPA) application tumor skin promotion protocol. Double application of TPA was undertaken to produce massive inflammatory and oxidative stress responses. Topical TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion. Vitamin E application 30 min prior to TPA treatment (10 nmol) inhibited induction of hydrogen peroxide, myeloperoxidase (MPO) activity, xanthine oxidase (XO) activity and lipid peroxidation (LPO). Vitamin E also positively modulated altered antioxidants of mouse skin. Histological examination also revealed marked improvement. These results confirm the efficacy of vitamin E against early inflammatory and oxidative stress responses, which are hallmark of tumor promotion and provide rational basis for chemopreventive action of vitamin E in skin cancer.

Protective effect of S-allylcysteine against cyclophosphamide-induced bladder hemorrhagic cystitis in mice.

S-Allylcysteine (SAC), an organosulfur compound of aged garlic extract (AGE) regulates the thiol status of the cell and scavenges free radicals. Depletion of thiols along with free radical generation has been implicated in cyclophosphamide (CP)-induced urotoxicity. We studied modulatory effect of SAC on CP-induced urotoxicity in mice focusing on hemorrhagic cystitis (HC). SAC (150 and 300 mg kg(-1)) was administered in CP treated animals (200 mg kg(-1)) and bladder was observed for histological and biochemical changes. CP treatment caused a marked increase in the lumen exudates, edema, vasodilation and HC in lamina propia in the bladder. These changes were accompanied by increase in lipid peroxidation (LPO), and decrease in reduced glutathione (GSH) and activities of antioxidant enzymes. SAC not only showed protection in tissue histology but also improved the decreased activities of antioxidant enzymes. SAC treatment also reduced LPO and increased GSH levels. Although SAC treatment did not ensure full recovery, the marked improvement in histology and antioxidants of bladder suggests that it has a significant modulatory effect on CP-induced urotoxicity. Since decrease in antioxidant level is the major cause of CP urotoxicity, the protective effect of SAC deserves its further exploration involving laboratory and clinical investigations.