Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex.

BACKGROUND: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex. Methodology/Principal Observations: We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control. CONCLUSION/SIGNIFICANCE: Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine's neuropsychological disorders including cognition and drug addiction.

Effect of oral administration of Bacillus coagulans B37 and Bacillus pumilus B9 strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model.

AIM: To investigate the effect of oral administration of two Bacillus strains on fecal coliforms, Lactobacillus and Bacillus spp. in rat animal model. MATERIALS AND METHODS: An in vivo experiment was conducted for 49-day period on 36 adult male albino Wister rats divided equally into to four groups. After 7-day adaptation period, one group (T1) was fed on sterile skim milk along with basal diet for the next 28 days. Second (T2) and (T3) groups received spore biomass of Bacillus coagulans B37 and Bacillus pumilus B9, respectively, suspended in sterilized skim milk at 8-9 log colony-forming units/ml plus basal diet for 28 days, while control group (T4) was supplied with clean water along with basal diet. There was a 14-day post-treatment period. A total of 288 fecal samples (8 fecal collections per rat) were collected at every 7-day interval starting from 0 to 49 days and subjected to the enumeration of the counts of coliforms and lactobacilli and Bacillus spores using respective agar media. In vitro acid and bile tolerance tests on both the strains were performed. RESULTS: The rats those (T2 and T3) received either B. coagulans B37 or B. pumilus B9 spore along with non-fermented skim milk showed decrease (p<0.01) in fecal coliform counts and increase (p<0.05) in both fecal lactobacilli and Bacillus spore counts as compared to the control group (T4) and the group fed only skim milk (T1). In vitro study indicated that both the strains were found to survive at pH 2.0 and 3.0 even up to 3 h and tolerate bile up to 2.0% concentration even after 12 h of exposure. CONCLUSIONS: This study revealed that oral administration of either B. coagulans B37 or B. pumilus B9 strains might be useful in reducing coliform counts accompanied by concurrent increase in lactobacilli counts in the intestinal flora in rats.

Developmental and neurobehavioural toxicity study of arsenic on rats following gestational exposure.

To characterize developmental and behavioral alterations induced by arsenic exposure, Albino rats were exposed to arsenic (0, 1.5, 3.0 and 4.5 mg/kg/day/po) from gestation day 8 to till parturition and the offspring were observed over the first 3 postnatal weeks, until they were weaned on post-natal day (PND) 21. Once the pups were delivered (PND0), the treatment was discontinued. All pups were assessed for physical development, reflex development, strength and motor coordination from standard neurobehavioural developmental test batteries beginning on PND1. Gestational administration of arsenic at tested dose levels, showed no significant changes in the day of appearance of eye opening, startle reflex, negative geotaxis and spontaneous alteration performance in comparison to the control group. The number of live fetuses, mean fetal body weight and percentages of resorptions or malformations per litter were not affected by arsenic exposure. No treatment-related malformations or developmental variations were noted at any exposure level, suggesting that arsenic exposure at this dose level did not adversely affect behavioural endpoints of developmental toxicity.

Effect of freeze drying process on some properties of Streptococcus thermophilus isolated from dairy products

The present investigation represents the effect of freeze drying on some properties as acid and bile tolerance of Streptococcus thermophilus MTCC 1938 culture isolated from dairy products. The cell paste obtained from milk based medium was freeze dried with a pressure of 50-100 mtorr for 24h at -40ºC. Acid and bile tolerance test exhibited 3.8-4.9 and 3.2-3.8 log counts reduction after freeze drying respectively.

Effect of freeze drying process on some properties of Streptococcus thermophilus isolated from dairy products.

The present investigation represents the effect of freeze drying on some properties as acid and bile tolerance of Streptococcus thermophilus MTCC 1938 culture isolated from dairy products. The cell paste obtained from milk based medium was freeze dried with a pressure of 50-100 mtorr for 24h at -40°C. Acid and bile tolerance test exhibited 3.8-4.9 and 3.2-3.8 log counts reduction after freeze drying respectively.

An experimental and clinical evaluation of anti-asthmatic potentialities of Devadaru compound (DC).

Devadaru compound was shown to be beneficial in Tamak Swasa (bronchial asthma). Clinical findings revealed higher percentage of relief in cardinal and general symptoms with decrement in the pulse rate and in the respiration rate. A significant linear increase in PEFR value was observed before and after treatment and an increase in FEV1 values measured in Group I subjects. There was relief of all symptoms in a significant number of patients. Occurrence of relief was observed only among patients who suffer less than 10 years duration with Tamak Swasa and among those the frequency of attacks of Tamak Swasa was at fortnightly or monthly intervals. Antispasmodic activity of Devadaru Compound (DC) on acetylcholine (Ach) induced contractions using rat ileum preparation was studied. The results demonstrated that DC inhibits Ach-induced contractions significantly and bears a dose-response relationship. This suggests that DC has got anti-spasmodic activity and corroborates the clinical findings. The clinical findings and experimental studies show that DC is of significant use in the treatment of Tamak Swasa (Bronchial Asthma) and superior to the standard and placebo therapy.

Potentiation of acetylcholine-induced smooth muscle contraction in rat ileum by lead.

The aim of this study was to find out lead interaction on acetylcholine-induced ileal (0.8 "to 1" longitudinal total strips) contractions in varying calcium (Ca++) or magnesium (Mg++) media and the cholinergic mechanism. Potentiation of ileal strips by lead (Pb++) remained dose-dependent as elicited by acetylcholine-induced contractions (1.81 x 10(-6) M to 1.28 x 10(-4) M). These were completely antagonized by atropine (1.01 x 10(-8) M). Lead (1.2 x 10(-5) M) potentiated contractions caused by acetylcholine in normal or in excess Ca++ media, but in low Ca++ or with various Mg++ media, lead failed to potentiate such contractions. Thus Pb++ has indirect cholinomimetic effect which involved extracellular Ca++.

Carbon disulphide induced sensitivity changes of rat anococcygeus muscle to noradrenaline (NA).

The sensitivity of rat anococcygeus muscle to noradrenaline (NA) was reduced following carbon disulphide (CS2) pretreatment. Preparations incubated in excess Ca++ (4.2 mmol.L-1) or Zero Ca++ (0.0 mmol.L-1) media showed decrease in sensitivity to NA. Reserpinization failed to induce supersensitivity to NA in any Mg++ concentration in the media. Reserpinized tissue in Mg++ free media with EDTA showed increased sensitivity while decreased sensitivity and maximum response to NA in Mg++ (1.2 mmol.L-1) and excess Mg++ (3.6m mol.L-1) concentration of the medium. In the presence of EDTA, the inhibition observed with CS2 in excess Mg++ (3.6m mol.L-1) medium was comparatively much less in both non-reserpinized and reserpinized preparations. In normal Ca++ and its deficient medium decrease in sensitivity to CS2 and the relevant maximum response to NA were observed. In excess Ca++, the CS2 effect depressed corresponding to its maximal response to NA. Thus CS2 may be inhibiting responses to NA by interfering with Ca++ utilization.

Magnesium and reserpine influence norepinephrine sensitivity of vas deferens in rats.

Reserpine induced supersensitivity to norepinephrine (NE) in rat vas deferens was sought by alteration of Mg++ and Ca++ concentration in incubation medium in the absence and presence of EDTA. Vas deferens incubated in Mg++ free and Mg++ excess media showed supersensitivity and subsensivity to NE respectively. Alterations in the sensitivity to NE produced by varying the concentrations of Mg++ were comparatively less. In the presence of EDTA, vas deferens obtained from reserpinized animals showed subsensitivity in normal and Mg++ excess media and supersensitivity in Mg++ free medium. In the presence of EDTA, reserpinized preparations showed slight supersensitivity in normal Mg++ medium, marked supersensitivity in Mg++ free and lesser subsensitivity in Mg++ excess medium. Probably EDTA by more effectively removing Mg++ from the membrane binding sites by chelation makes the membrane permeable to Ca++ leading to supersensitivity to NE (observed only in the presence of EDTA). These results suggest that the failure of reserpine to induce supersensitivity to NE in rat vas deferens may be due to an enhanced antagonism of Mg++ on Ca++ movements in this preparations due to the poor capacity of rat tissue to retain Ca++.

Lithium effect: review on chemico-biologic interactions.

Lithium affects nerve excitation, synaptic transmitter and neuronal metabolism. These effects may be produced by alteration of ions transport or distribution, by inhibition of adenyl cyclase mediated responses or by more direct interference with neuronal metabolism. Which of these effects is responsible for the therapeutic benefit in mania, if any, is still unknown. This state of ignorance is directly related to conflicting interpretations and incomplete understanding of the manic state itself.

Inhibitory effect of lead on 5-hydroxytryptamine induced contractions of isolated ileum of rat.

The present study examined the effects of lead (Pb) on the 5-hydroxytryptamine (5-HT) contracture and calcium (Ca++) kinetics of ileum of rat. Isolated ileum preparations incubated in excess Ca++ (2.8 mM) or in Ca++ free Tyrode solution showed decrease in sensitivity to 5-HT. The inhibitory action of Pb reduced the sensitivity and decrease maximum responses to 5-HT in any Mg++ concentration of the medium. In the normal Ca++ and its deficient medium deterioration in sensitivity to Pb and the relevant maximum response to 5-HT were observed. In excess Ca++, the Pb effect depressed corresponding to its maximal response to 5-HT. The presence of EDTA depressed the Pb effect irrespective of the Ca++ influence on the receptors. Thus Pb may be inhibiting responses to 5-HT by interfering Ca++ utilization.

Effects of hexachlorocyclohexane (HCH) on the contractile response induced by norepinephrine in the rat isolated vas deferens.

Effects of hexachlorocyclohexane (Technical HCH) on the contractile responses of rat isolated Vas deferens to norepinephrine (NE) were investigated by varying the Ca++ and Mg++ concentrations of the incubation medium. Preparations incubated in excess Ca++ (4.2 mM) or in Ca++-free Krebs solution showed decrease in sensitivity to NE. The inhibitory action of HCH reduced the sensitivity and decreased maximum responses to NE in any Mg++ concentration of the medium. In the normal Ca++ and its deficient medium decrease in sensitivity to HCH and the relevant maximum response to NE were observed. In excess Ca++, the HCH effect depressed corresponding to its maximal response to NE. The presence of EDTA depressed the HCH effect irrespective of the Ca++ influence on the receptors.

Histological and pharmacological changes in vas deferens of rats exposed to hexachlorocyclohexane.

The effect of hexachlorocyclohexane (HCH) treatment in male albino rats at dosages of 3 and 6 mg/kg body weight by force-feeding were studied over a period of 180 days. Histological observations revealed graded degeneration in the muscular layer of vas deferens. Moreover, the accumulation of HCH residue in serum and vas deferens is highly significant in the experimental group. The contractility of muscles showed marked inhibition by in vitro study.

Benzidine and its acetylated metabolites in the urine of workers exposed to Direct Black 38.

Urine samples of workers in a small-scale unit manufacturing Direct Black 38 were analyzed by high-pressure liquid chromatography for the presence of benzidine and mono and diacetyl benzidine. Acetylated metabolites were found in all the urine samples, and benzidine was found in all except two. Two workers excreted very high levels of benzidine and its metabolites in their urine. This study highlights the potential risk of bladder cancer in such units of developing countries where manufacture of benzidine-based dyes is yet to be regulated.

Toxic effect of lead on the testes of rat.

Biochemical and histopathological studies were performed on the testes of rats after feeding lead acetate at a concentration of 0.25, 0.50 and 1.0 g/l over a period of 60 days. Testicular atrophy along with cellular degeneration was conspicuous at 1 g/l. Furthermore, high cholesterol concentration and significantly low ascorbic acid concentration were found in the testes at the same dosage. The lowest dose (0.25 g/l) did not produce any significant morphological and biochemical alteration whereas 0.5 g/l resulted in partial inhibition of spermatogenesis.

influence of Mg++ and reserpine on the reactivity of rat seminal vesicle to 5-hydroxytryptamine.

The effects of varying the concentration of Mg++ in the incubation medium on the contractile responses of rat isolated seminal vesicle to 5-hydroxytryptamine (5-HT) were investigated in the absence and presence of EDTA. Preparations incubated in Mg++-free and Mg++ excess media showed supersensitivity and subsensitivity to 5-HT respectively. In the presence of EDTA alterations in the sensitivity to 5-HT produced by varying the concentrations of Mg++ were comparatively less. Preparations obtained from reserpinized animals showed subsensitivity in normal and Mg++ excess media and supersensitivity in Mg++-free medium. In the presence of EDTA, reserpinized preparations showed slight supersensitivity in normal Mg++ medium, marked supersensitivity in Mg++-free medium and lesser subsensitivity in Mg++ excess medium. Probably EDTA by more effectively removing Mg++ from the membrane binding sites by chelation makes the membrane permeable to Ca++ leading to supersensitivity to 5-HT (observed only in the presence of EDTA). These results suggest that the failure of reserpine to induce supersensitivity to 5-HT in rat seminal vesicle may be due to an enhanced antagonism of Mg++ on Ca++ movements in this preparation due to the poor capacity of rat tissue to retain Ca++ (Krishnamurty and Grollman, 1976).

Blockade of 5-hydroxytryptamine-induced responses of rat seminal vesicle by lithium-possible mediation through calcium exchange..

Effect of lithium on the contractile responses of rat isolated seminal vesicle to 5-hydroxytryptamine (5-HT) were investigated by varying the Ca++ and Mg++ concentrations of the incubation medium in the absence and presence of EDTA. Preparations incubated in excess Ca++ (4.2 mM) or in Ca++-free Krebs solution showed decrease in sensitivity to 5-HT, whereas the responses to 5-HT were potentiated in Mg++-free incubation media and reduced in media containing excess Mg++. Rezerpinization failed to induce supersensitivity to 5-HT in any Mg++ concentration in the medium. However, reserpinized tissue in Mg++-free solution with EDTA showed increased sensitivity to 5-HT. Li+ inhibited responses to 5-HT. The inhibitory action of Li+ was augmented in medium lacking in Ca++ and was antagonized in media containing excess Ca++ (4.2mM). Li+ reduced the sensitivity and decreased maximum responses to 5-HT in any Mg++ concentration in the medium. In the presence of EDTA, the inhibition observed with Li+ in excess Mg++ (3.6 mM) medium was comparatively much less in both non-reserpinized and reserpinized preparations. Thus Li+ may be inhibiting responses to 5-Ht by block of influx of Ca++ or delayed efflux of Ca++ or inhibition of uptake of Ca++ or a combination of two or more of these effects.