Dichlorophene activates aryl hydrocarbon receptor (AhR) and indoleamine 2, 3-dioxygenase 1 (IDO1) to mediate splenotoxicity in rat.

Dichlorophene (DCP) is a halogenated phenolic compound, widely used as fungicide, bactericide and antiprotozoan and also exhibit therapeutic application in several pathological conditions. Taking account of broad use of DCP, its possible effect on spleen (an important immune organ) was investigated in this study. Male albino rats were treated with graded doses of DCP (10%, 20% and 30% of LD50) and spleen and blood were obtained at 24, 48 and 72 hours post treatment. Oxidative stress parameters, proinflammatory cytokines and protein expression of aryl hydrocarbon receptor (AhR), indoleamine-2, 3-Dioxygenase 1 (IDO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were measured along with histopathological evaluation of spleen. In the present study, DCP perturbs redox status of splenocytes of rats as evidenced by excess ROS generation, lipid peroxidation and nitric oxide production simultaneously with reduction of antioxidant level [glutathione (GSH)] and inhibition of antioxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)]. Two important proinflammatory cytokines, IL-6 and TNF-α were found to be elevated upon DCP treatment. Moreover, DCP also caused activation of AhR and IDO1 with simultaneous down regulation of Nrf2. All these effects of DCP were found to be dose and duration dependent. DCP also affects the spleen micro-architecture in the present study and these alterations were more prominent in high dose group at 72 hours post treatment. Taken together, all these results suggested that DCP induces oxidative stress and also increases proinflammatory cytokine levels to mount its toxic effect on spleen.

Synergistic protective effect of folic acid and vitamin B12 against nicotine-induced oxidative stress and apoptosis in pancreatic islets of the rat.

CONTEXT: Nicotine is an abundant and most significant component of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury, although effects of smoking on endocrine pancreas are still controversial. OBJECTIVE: We examined the impact and underlying mechanisms of action of folic acid and vitamin B12 on nicotine-induced damage in pancreatic islets of rats. MATERIALS AND METHODS: Male Wistar rats were treated with nicotine (3 mg/kg body weight/d, intraperitonealy) with or without folic acid (36 µg/kg body weight/d, orally) and vitamin B12 (0.63 µg/kg body weight/d, orally) for 21 d. Fasting blood glucose, oral glucose tolerance test, HBA1c, insulin, oxidative stress parameters, proinflammatory cytokines, and CRP level were measured. Histological evaluation, TUNEL assay, and immunohistochemical staining of NF-κB and caspase-3 were also performed. RESULTS: Folic acid and vitamin B12 blunted the nicotine-induced impairment in fasting blood glucose (51-56% recovery), HbA1c (64-76% recovery), oral glucose tolerance, insulin level (23-40% recovery), and islet cell counts (26-74% recovery) in rats. Moreover, folic acid in combination with vitamin B12 also attenuated the nicotine-induced changes in markers of oxidative stress (17-88% recovery), TNF-α (40-99% recovery), and IL-6 level (47-65% recovery), CRP level (59-73% recovery), expression of NF-κB and caspase-3, and apoptosis in pancreatic islet cells. DISCUSSION AND CONCLUSION: The present study shows that folic acid and vitamin B12 supplementation can reduce nicotine-induced impairment in glucose homeostasis and apoptosis and damage of pancreatic islet cells by modulating oxidative stress, levels of proinflammatory cytokines, and expression of NF-κB.

Association between duration of coal dust exposure and respiratory impairment in coal miners of West Bengal, India.

Purpose. The prevalence and severity of respiratory disorders are very high among coal miners as continuous exposure of workers in such an environment leads to accumulation of dust in the lungs. This study was designed to assess the prevalence of lung function impairment and to determine whether there is any correlation between dust exposure duration and lung function indices. Materials. Two hundred and thirty underground coal dust-exposed workers and 130 age-matched non-exposed workers were recruited from an underground mine in West Bengal, India. A spirometry test was performed for lung function and also basic information on personnel's dust exposure, smoking and respiratory morbidity was collected. Student's t test, Pearson's correlation coefficient (r), uncorrected Pearson's χ2 test and Fischer's exact test were performed for statistical analysis. Results. Lung function indices were significantly (p < 0.050) impaired between the exposed (43.91%) and non-exposed (23.85%) groups. In addition, highly significant decrements in the pulmonary volumes of exposed subjects were also noted. Furthermore, a high negative correlation was observed between spirometric results and exposure time in the exposed group compared with the non-exposed group. Conclusion. This study suggested a positive relationship between exposure time and lung function deterioration.

Radioprotective effect of ethanolic extract of Alocasia indica on γ-irradiation-induced reproductive alterations in ovary and uterus.

Evaluation of the modulatory effect of ethanolic extract of Alocasia indica tuber (EEAIT) against γ-irradiation induced ovarian and uterine toxicity. Extract preparation was done by 80% hydro-ethanol using Soxhlet apparatus. EEAIT was administered to female Swiss albino mice (n = 5) daily (200 and 400 mg/kg body weight/d) for 7 days before γ-irradiation exposure (2.9 Gy). FSH, LH, estrogen, progesterone, cytokine levels, and oxidative stress parameters were measured after 24 hours of γ-irradiation. Histology, folliculogenesis, viability of granulosa cells, ROS measurement by flow cytometry, western blot of P450scc, P45017A1, 3ß HSD and SF 1 were also performed. In addition, fertility status was assessed by fecundability and fecundity. The results showed that EEAIT exhibit a strong radioprotective activity by reducing the oxidative stress and thereby restored the ovarian and uterine alterations. EEAIT also improved the abnormality in follicle development, restored altered gonadal hormones and cytokines levels, increase the fertility status, reducing ROS level of granulosa cells with increasing granulosa cells viability and steroidogenic enzyme activity as compared to control. So EEAIT showed a radioprotective effect on γ-irradiation induced ovarian and uterine damage. Our results suggested that Alocasia indica tuber can be a potential radioprotector to prevent female infertility.