Effect of n-Butanol on chromosomal damage in mice bone marrow cells

Background: n-Butanol is a four-carbon alcohol used widely in foods, cosmetics industries, biology and chemistry research laboratories, and other fields. Long time-effects of inhalation or consumption of small amounts of Butanol on human health are still unknown. On the other hand, numerous reports about the development of n-Butanol toxicity are available. The main objective of the study was to investigate the effects of inhaled and oral administration of n-Butanol as a long-term in vivo investigation

Materials and Methods: small white laboratory, male mice [20-30 g] were used in 11 groups [n=4] including experimental 1 to 6, 1 to 4 control "A" and positive control groups. Experimental groups 1-3, for 10, 20, and 40 days; 5 hours a day were inside a box with ventilation facilities exposed to air saturated with n-Butanol vapor. Experimental groups 4 to 6, received water containing n-Butanol 0.2%, 1% and 5% for 10 days. Control groups B, 1 to 3 was placed for 10, 20, and 40 days inside a similar box exposed to normal air, respectively. Control group B 4 received water without any particular substance for 10 days. The positive control group received 30[micro]l subcutaneous vinblastine. Bone marrow cells were extracted 24 hours after treatments and stained by May-Grünwald-Giemsa staining and the number of micronucleus was counted. Vinblastine, as a positive control, increased an average of micronucleus numbers significantly compared to control group [P<0.001]

Results: n-Butanol inhalation caused no significant difference in 1-3 experimental groups in the average numbers of micronucleus compared to control group, even in the 40 days treatment group, average numbers of micronucleus was decreased comparing to control group [P<0.05]. Also, oral administration of 0.2% and 1% n-Butanol had no effect on the average micronucleus numbers compared to the control group, while oral administration of 5% n-Butanol caused even decrease in average numbers of micronucleus compared to control group [P<0.05]

Conclusion: n-Butanol inhalation may not cause chromosome damages in rat bone marrow cells that probably is due to its very fast metabolism and decomposition in the body. Therefore, the amount of n-Butanol in the systemic circulation and tissues is very low and, probably, the damaging potential is decreased

Effects of neonatal capsaicin treatment on stress induced analgesia and hyperalgesia in Tail-Flick test in male rats

Background & Objective: It is reported that acute forced swimming stress induces analgesia immediately, and chronic stress induces hyperalgesia. Whereas in response to nociceptive stimulation, small-diameter C-fibers of the excitatory system in the dorsal horn of the spinal cord are activated, therefore, in the present study, the effects of C-fiber lesion in stress and dexamethasone-induced analgesia and hyperalgesia in acute and chronic forms were investigated using Tail-Flick test. Methods: Adults Wistar male rats (180-200 g) were assigned into three groups (n=7): C-normal (intact C-fibers), sham (received capsaicin vehicle at neonate stage) and C-lesion (received capsaicin at neonate stage). Forced swim stress (10 min/day) in water (18±1 ºC) was considered as acute stress and repeated daily forced swim stress as chronic stress, also single-dose of dexamethasone (2 mg/kg, i.p.) was considered as acute dexamethasone and repeated for three days as chronic dexamethasone. Neonatal capsaicin treatment was used for C-fibers depletion. The nociceptive thermal threshold was assessed using Tail-Flick test. Results: In C-lesion group, thermal pain sensitivity was reduced (P<0.001). Acute stress in C-normal group, reduced pain (P<0.001) and in C-lesion group, it caused deeper antinociception in Tail-Flick (P<0.001). Chronic stress and acute-chronic dexamethasone in C-normal group, created hyperalgesia (P<0.001) and induced analgesia in C-lesion groups (P<0.01). Conclusion: It seems that presence of C-fiber is so important in thermal pain transmission in Tail-Flick test; therefore, C-fiber lesion, reduces pain sensitivity (analgesia), increases antinociception effects of acute stress, decreases hyperalgesia of chronic-stress and acute-chronic dexamethasone

[Effect of intraperitoneal and intrathecal administration of ascorbic acid and sodium ascorbate on pain in rat]

Ascorbic acid [ASC] is abundant in the brain. ASC is effective on synthesis and transportation of neurotransmitters. Glutamatergic system is involved in pain transduction. NMDA receptors can be inhibited, and TPRV1 and ASIC receptors are excited due to its acidity at the presence of ASC. Therefore, this study is aimed to investigate the effects of intraperitoneal [i.p] and intrathecal [i.t] administration of ASC and sodium-ascorbate on pain. Male Wistar rats [200-250 g] in eight groups [n=7] included saline [i.p], saline [i.t], ASC [1, 10, 100, 200 mg/kg, i.p], usual and neutralized ASC [0.02 mg/10 micro l, i.t] were used. Pain threshold was measured by tail-flick test and chemical pain was assessed using formalin-test. ASC [10, 100, 200 mg/kg, i.p] induced hyperalgesia in tail-flick test [P<0.01] and reduced pain in formalin-test [P<0.05], but ASC [1 mg/kg i.p] with no effect in tail-flick, decreased pain during formalin-test interphase [P<0.01]. Intrathecal ASC at 0.02 mg/10 micro1 concentration, but not sodium-ascorbate, induced hyperalgesia in tail-flick test [P<0.001]. ASC [0.02 mg/10 microl, i.t] in both forms of usual and sodium-ascorbate, decreased pain in formalin-test [P<0.001]. Lesser inhibition effects of ASC on AMPA receptors may be responsible at least in part for its hyperalgesia in tail-flick test at i.p administration. This plus the sensitivity of TRPV1 and ASIC receptors to ASC acidity can be considered for i.t administration, because sodium-ascorbate [i.t] didn't induce hyperalgesia. Inhibiting effects of i.p and i.t administration of ASC and sodium-ascorbate on NMDA receptors, release of SP and other inflammatory mediators, were probably some players of pain reduction during the formalin-test

[ effect of intrathecal administration of cocaine and serotonergic antagonist [cyproheptadine] on nociception in rat]

Cocaine by effect on central nervous system inhibits reuptake of monoamines [serotonin, norepinephrine and dopamine] to presynaptic terminal and increases their concentration. Monoamines such as serotonin cause analgesia at the spinal level. This study investigates the effects of systemic and spinal administration of cocaine on pain sensation and the relation between these effects and serotonin. Male Wistar rats [200-250g] were set in groups: saline [i.p], saline/DMSO [i.p], cocaine 25mg/kg [i.p], saline [i.t], saline/DMSO [i.t], cocaine 100micro g/10 micro l [i.t], cyproheptadine 33 micro g/10 micro l [i.t.] and cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t]. Tail flick latency was measured before and after administration. Intraplantar formalin was used for induction of chemical pain. The data was analyzed by T-Test and ANOVA. Pain in both phases of formalin test was reduced in both cocaine 25mg/kg [i.p] [P<0.01] and cocaine 100 micro g/10 micro l [i.t.] [P<0.01]. However, in cyproheptadine 33 micro g/10 micro l [i.t], was increased in the first phase [P<0.01]. In cyproheptadine 33 micro g/10 micro l/cocaine 100 micro g/10 micro l [i.t.], the part of pain reduction induced by cocaine was reversed, in both phases [P<0.01]. In tail flick test the results of cyproheptadine 33 micro g/10 micro l [i.t.] showed reduced tail flick latency [P<0.001]. Inhibition of serotonin reuptake at the spinal level plays role in analgesic effects of cocaine probably, because release of serotonin from the spinal serotonergic terminals causes inhibition of pain neurons and reduction of pain. In addition, inhibition of spinal serotonin receptors by cyproheptadine reduced part of analgesic effects of cocaine probably

Effect of Oseltamivir on hyperalgesia induced by low concentrations of morphine and morphine tolerance in Drosophila melanogaster

Introduction: Morphine has been known as a drug with different paradoxical effects, analgesic and hyperalgesic. On the other hand, repeated morphine administration, induces morphine tolerance in mammals. The aim of recent study is investigating tolerance to morphine in Drosophila melanogaster and the effect of Oseltamivir [an inhibitor of G2 receptors] on hyperalgesia induced by low concentrations of morphine and morphine tolerance

Materials and methods: In this study, stage 3 of larvae and adult state of wild Drosophila melanogaster were used. For evaluating the effect of Oseltamivir on hyperalgesic effect of low concentration Morphine, Oseltamivir [0.2 mg/l] and low concentrations of morphine were added to media culture. Then behavior of larvae and adults to thermal [using Hot plate, 47°C] and chemical [capsaicin and acetic acid] pain stimulations were recorded. For morphine tolerance experiments in larvae, repeated morphine administration [0.1 and 0.01 mg/l] was done and their response to thermal pain was evaluated. The same method was used in adults but with other doses of morphine [200 and 300 mg/l]. Finally to investigate the mechanism of morphine tolerance, Oseltamivir was administered too

Results: morphine tolerance was occurred in Drosophila melanogaster similar to mammals. Repeated morphine administration diminished anti nociceptive effects of morphine [p<0.001]. Oseltamivir reduced morphine tolerance and hyperalgesic effects of low concentration morphine in both pain models [thermal and chemical nociception], [p<0.01]

Conclusion: opioid systems can involve pain modulation [hyperalgesia and analgesia] in Drosophila like vertebrates. Our results showed inhibition of excitatory G-protein [Gs] by Oseltamivir, inhibit morphine induced hyperalgesia and this is another confirmation for involvement of excitatory G-proteins in morphine induced tolerance

[ vitro histological investigation of interactions between rat's mesenchymal stem cells and human gingival matrix]

Extracellular matrix of natural tissues can be used as a scaffold for reconstructing biological tissues and organs. In this study, decellularized human gingival matrix was used as a scaffold for investigating the interactions of rat's bone marrow mesenchymal stem cells with human gingival matrix. To reach this goal, human gingival tissues were decellularized by two detergents sodium dodecyl sulfate [SDS] and Triton X-100. After washing and sterilization procedures, scaffolds were divided into 3 groups. Low density [LD] group was cultivated with 8x104 cells /cm2, high density [HD] group was cultivated with 8x105 cells/cm2, and control [C] group, was maintained in culture medium without any cells. Microscopic sections were prepared from the scaffoldsbefore and after 1, 2 and 4 weeks of culture with mesenchymal cells and were stained with Hematoxylin-Eosin. Repeated measure ANOVA was used to study the cell density alteration significance within the matrixes and post tests of means comparisons were performed within and between the groups. Also, gingival samples before and after decellularization procedure were investigated by scanning electron microscopy. Histological study of decellularized scaffolds revealed that nuclear and cellular components of the tissues were completely removed. Scanning electron microscopy of the scaffolds indicated that collagen fibers of connective tissue remained intact. Study of the scaffolds 1, 2 and 4 weeks after culture, revealed penetration of mesenchymal stem cells in scaffold, migration of cells towards connective tissue's papilla, and moreover epithelium-like structures. Statistical analysis indicated that cell density in HD group was significantly [P<0.05] higher than LD group. Cell density in both LD and HD groups significantly increased at 2nd week and decreased after4 weeks of culture. According to the results, scaffolds prepared from human gingival matrix can be a suitable scaffold for studying In vitro cell behaviors during oral wound healing

[Effects of repeated anesthesia by thiopental in neonatal period on PTZ-induced convulsions and pain responses during maturation in rats]

General anesthetics during critical periods of brain development may cause some serious malformations or side effects. Anesthetic drugs can involve in the brain development and synaptogenesis at the critical period of development. There are some controversy with regards the effects of [neurodegenerative or neuroprotective] barbiturates on brain. The aim of the present study was to investigate the possible relation between repeated induced thiopental [a GABAA agonist] anesthesia at the postnatal period and pentylentetrazol-induced convulsions and pain responses in adult in the Wistar rats. 40 male neonate rats were divided into experimental and sham groups. The experimental group [n=20] was deeply anesthetized with thiopental [30 mg/kg daily] during 10 to 20-days of post- natal period and physiologic serum was used for sham animals. After maturation of male rats, the PTZ-induced seizures were induced by daily interapritoneally injection of PTZ [45 mg/kg], and the latency of the appearance of generalized epileptiform behaviors was recorded. Pain responses were also evaluated using tail-flick and formalin tests. No significant differences were found in the lantency of the appearance of behavioural convulsions and pain sensitivity between experimental and sham groups. Our findings indicate that prior exposure to thiopental during nenonatal stage has no effects on PTZ-induced seizures and also pain responses after maturation. Developmental compensatory mechanisms may protect the brian against the possible damage that induced by repeated thipopental during neonatal period.