MATERIAL AND METHODS: A) Effects of various doses of nicotine on in vitro embryonic development: Female mice were treated with 1.0, 3.0, or 5.0 mg/kg/day nicotine for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured in vitro. Plasma was assayed. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Female mice were treated with nicotine (5.0 mg/kg/day), gavaged gamma-TCT of 30, 60, or 90 mg/kg/day or nicotine concurrently with gamma-TCT of 3 different doses for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured and plasma was assayed.
RESULTS: A) Effects of various doses of nicotine on in vitro embryonic development: Number of hatched blastocysts decreased in 1.0 and 3.0 mg/kg/day nicotine groups. Nicotine at 5.0 mg/kg/day stopped embryo development at morula. MDA concentrations increased following all nicotine doses. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Embryo development was completed in all groups. MDA concentration increased only in the group treated with nicotine concurrently with 30 mg/kg/day gamma-TCT.
CONCLUSIONS: Nicotine impairs in vitro embryo development and increases MDA in plasma. The deleterious impact of nicotine on embryo development is reversed by supplementing gamma-TCT concurrently with nicotine.
METHODS: This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C, α-tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared.
RESULTS: The TBARS level was found to be significantly higher (p≤0.001) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance (p≥0.05) was observed in the level of vitamin C and α-tocopherol. GSH and TAA level were significantly decreased (p≤0.001) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit.
CONCLUSION: Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development.
AIMS: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators.
SETTINGS AND DESIGN: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls.
MATERIALS AND METHODS: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR).
RESULTS: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls.
CONCLUSION: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.
Methods: Human neuroblastoma cells SH-SY5Y (as a neuronal model) and human glioblastoma cells T98G (as an astrocytic model), were treated with 100-500 µM PA, oleic acid (OA) or lauric acid (LA) for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ), a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS) level was determined using 2',7'-dichlorofluorescien diacetate (DCFH-DA) assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS) assay.
Results: MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA's neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity-suggesting a mechanism of PA-induced leptin resistance. Annexin V/PI flow cytometry analysis revealed PA-induced increase in percentages of cells in annexin V-positive/PI-negative quadrant (early apoptosis) and subG0-G1 fraction, accompanied by a decrease in G2-M phase cells. The PA-induced ROS production and lipid peroxidation was at greater extent in T98G as compared to that in SH-SY5Y.
Discussion: In conclusion, PA induces apoptosis by increasing oxidative stress in neurons and astrocytes. Taken together, the results suggest that HFD may cause neuronal and astrocytic damage, which indirectly proposes that CNS pathologies involving neuroinflammation and reactive gliosis could be prevented via the diet regimen.