Verapamil contributes to the clastogenic effects of acrylamide, cyclophosphamide, and dioxidine on somatic cells of BALB/C and C57BL/6 mice

The chromosome aberration assay of metaphase bone marrow cells was used to study the clastogenic effects of acrylamide, cyclophosphamide, dioxidine, and their combinations with Verapamil (a calcium antagonist) in male BALB/C and C57BL/6 mice. Verapamil gavage at single (5 mg/kg) and repeated doses (2.5 and 5 mg/kg five times at 24-h intervals) significantly enhanced the clastogenic activity of acrylamide (50 and 100 mg/kg intraperitoneally) in BALB/C mice; in C57BL/6 mice, this effect was only observed when they received Verapamil at doses of 2.5 mg/kg for 5 days. Verapamil administered repeatedly (2.5–10 mg, gavage) significantly increased the clastogenic activity of cyclophosphamide (10 mg/kg intraperitoneally) in C57BL/6 mice. In BALB/C mice, this effect of Verapamil was only observed at a dose of 10 mg/kg (gavage). When injected intraperitoneally at a single dose of 0.1–0.4 mg/kg, Verapamil significantly enhanced the clastogenic activity of cyclophosphamide in mice of both strains. This calcium antagonist produced identical effects when administered to BALB/C mice intraperitoneally (2.5 and 5 mg/kg) and by gavage (5 mg/kg) and to C57BL/6 mice intraperitoneally (5 and 10 mg/kg) and by gavage (2.5 mg/kg). Repeated administration of Verapamil (at all doses tested) promoted the clastogenic effect of dioxidine (100 mg/kg intraperitoneally) on C57BL/6 mice, having no such influence on BALB/C mice. These results demonstrate the co-clastogenic activity of Verapamil in mice and suggest that its specific manifestations depend on the dose, method, and route of drug administration and the genotype of test animals.     

Influence of acetylcysteine on cytogenetic effects of etoposide in mouse oocytes

The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F₁ CBA × C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice.     

Diazinon-induced ulcerative keratitis in C57bl/6 mice

As a well-known organophosphate insecticide, diazinon (DZN) has been used for several decades in agriculture. The major signs of ophthalmic toxicity of DZN have been reported to be cholinergic overstimulation (lacrimation, myosis). Here, we report, for the first time, ulcerative keratitis in C57bl/6 mice secondary to sub-acute exposure to DZN. Four groups of female C57bl/6 mice were administered intraperitoneally either DZN (1, 5, 25 mg/kg/day) or vehicle for 14 consecutive days. Then, histopathological examinations on mice eyes were performed using light microscope and scored for corneal keratitis. Furthermore, blood cholinesterase activity, and hematologic examinations were performed. Data indicated a significant ulcerative keratitis with prompt vision loss in mice exposed to 25 and 5 mg/kg/day (P < 0.05) doses. These results suggest that diazinon might induce ulcerative keratitis secondary to its immunosuppresive effects at high doses in C57bl/6 mice.     

Kinetics of ectromelia virus (mousepox) transmission and clinical response in C57BL/6j, BALB/cByj and AKR/J inbred mice

Research was undertaken to answer basic questions on susceptibility, clinical response and transmission of ectromelia virus in selected strains of inbred mice. C57BL/6J and AKR/J were found to be markedly more resistant to a virulent strain of ectromelia virus (isolated during the 1979-80 outbreak at the National Institutes of Health) than C57LJ, BALB/cByJ, DBA/2J, A.By/SNJ and C3H/HeJ when infected by footpad inoculation. In C57BL/6J and AKR/J the LD50 was about 7 logs higher than the ID50. With one exception, C57LJ, the LD50 and ID50 titers in the other strains were about equal. In C57LJ the LD50 titer was intermediate. Following intragastric inoculation, virus was isolated from feces of C57BL/6J mice for as long as 46 days and up to 29 days from BALB/cByJ mice. Transmission to cage mates from intragastrically infected C57BL/6J and BALB/cByJ occurred up to 36 and 30 days respectively after infection. Virus was isolated from the spleen in 2 of 5 BALB/cByJ mice and 1 of 7 C57BL/6J mice tested 95 days after gastric inoculation. Following footpad inoculation, BALB/cByJ mice consistently transmitted virus to cage mates before death at 10-12 days. C57BL/6J mice transmitted between days 8 and 17, but not beyond. Virus was maintained in C57BL/6J mice by exposure to infected cage mates for seven passages, which was the most attempted. Clinical signs in infected C57BL/6J mice were usually subtle or inapparent.     

Genetic variation in testicular development in mice of the C57BL/10ScSn, C57BL/6By and BALB/cBy strains and the CXB recombinant-inbred lines

When compared with C57BL/6By mice, BALB/cBy mice had testes that were 41% heavier at 60 days of age and seminiferous tubules that were 41% greater in cross-sectional area at 120 days. Absolute testicular weight did not increase between 60 and 120 days of age in either C57BL/6By or C57BL/10ScSn mice but did in BALB mice, paralleling changes in the size of the seminiferous tubules. Significant testicular growth took place over this age period in mice of all seven of the CXB recombinant-inbred (RI) strains of mice derived from a cross of the BALB/cBy and C57BL/6By strains. The wide range of phenotypes shown by adult recombinant mice, which ranged from those with significantly heavier testes than BALB to those with testes the same size (at 60 days) as those of C57BL/10ScSn mice, implied the existence of several separable factors affecting testicular size in adults. At 30 days of age the RI lines fell into two groups; one with small testes like C57BL/6By and the other with larger testes like BALB/cBy mice. The segregation pattern for prepubertal testicular weight was identical to that for the H-2 histocompatibility locus.     

Mouse strain differences in induction of micronuclei by base analogues and nucleosides

The frequency of induced micronucleated polychromatic erythrocytes (MNPCEs) was compared in BALB/c, C57BL/6, and DBA/2 mice after intraperitoneal (i.p.) injection of 5-bromodeoxyuridine (BUdR), 5-fluorodeoxyuridine (FUdR), cytosine arabinoside (Ara-C), 6-mercaptopurine (6-MP), 5-bromouracil (5-BU), thymidine (TdR), uridine (UdR), adenosine (AdR) and guanosine (GdR). The experimental procedure was a single i.p. injection followed by harvest at 30 h. The frequency of MNPCEs was significantly increased in all strains by treatment with BUdR, FUdR, Ara-C and 6-MP compared to vehicle control. TdR and UdR induced MNPCEs slightly in BALB/c mice but showed no effect on C57BL/6 and DBA/2 mice. 5-BU, AdR, and GdR did not increase the frequency of MNPCEs in any mouse strain used. These results suggest that BALB/c mice are more susceptible to induction of MNPCEs by clastogenic base analogues and nucleosides than are C57BL/6 or DBA/2 mice.     

Comparative effects of endrin on hepatic lipid peroxidation and DNA damage,and nitric oxide production by peritoneal macrophages from C57BL/6J and DBA/2 mice

1. Endrin is a polyhalogenated cyclic hydrocarbon which produces hepatic and neurologic toxicity. In order to further assess the mechanism of toxicity ofendrin, the dose-dependent effects of endrin on hepatic lipid peroxidation and DNA damage, and nitric oxide (NO) production by peritoneal exudate cells (primarily macrophages) were investigated in C57BL/6J and DBA/2 mice which vary at the Ah receptor genetic locus. C57BL/6J mice are dioxin-responsive, while DBA/2 mice are dioxin-insensitive.2. Mice of both strains were treated with 0, 1, 2 or 4 mg endrin kg⁻¹ as a single oral dose in corn oil, and the animals were killed 24 hr post-treatment. At doses of 1,2 and 4 mg endrin kg⁻¹ in C57BL/6J mice, hepatic mitochondrial lipid peroxidation increased 1.2-, 2.2- and 3.2-fold, respectively, and 1.8-, 2.3- and 3.5-fold with microsomes, respectively. At these same doses in DBA/2 mice, hepatic mitochondrial lipid peroxidation increased 1.3-, 2.0- and 2.6-fold, respectively, and 1.5-, 1.9- and 2.5-fold with microsomes, respectively.3. Increases of 2.3-, 2.4- and 4.9-fold were observed in hepatic DNA damage (elution constants) in C57BL/6J mice at doses of 1, 2 and 4 mg endrin kg⁻¹, respectively, while at these same three doses, increases of 1.9-, 2.1- and 2.3-fold were observed for DBA/2 mice, respectively.4. Nitric oxide production by peritoneal macrophages from C57BL/6J increased by 1.3-, 1.7- and 2.0-fold with doses of 1, 2 and 4 mg endrin kg⁻¹, respectively, while in macrophages from DBA/2 mice at these same doses, increases of 1.7-, 1.7- and 1.8-fold, respectively, were observed.5. The results indicate that the responsiveness of peritoneal macrophages with respect to both DNA damage and nitric oxide production are more dose-dependent in C57BL/6J mice as compared to DBA/2 mice, while similar results are observed with the lipid peroxidation of hepatic mitochondria and microsomes of the two mouse strains. The results suggest that the toxicity of endrin is less reliant on a mechanism which may involve the Ah receptor system as compared to dioxins as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).     

Effects of iNOS inhibitor on IFN-gamma production and apoptosis of splenocytes in genetically different strains of mice infected with Toxoplasma gondii

To evaluate the role of nitric oxide (NO) in IFN-gamma production and apoptosis of splenocytes in genetically different strains of mice with toxoplasmosis, BALB/c (a toxoplasmosis resistant strain) and C57BL/6 (a toxoplasmosis susceptible strain) mice were infected with Toxoplasma gondii cysts orally and subsequently injected intraperitoneally with aminoguanidine, an iNOS inhibitor (AG; 35 mg/kg per mouse daily for 14 days). When BALB/c or C57BL/6 mice were infected with T. gondii without AG treatment, number of brain cysts, NO and IFN-gamma production by splenocytes, and percentages of apoptotic splenocytes were increased compared to uninfected control mice without AG treatment. AG treatment increased the number of brain cysts, and reduced NO and IFN-gamma production in T. gondii-infected C57BL/6 mice. In contrast, in T. gondii-infected BABL/c mice, the number of brain cysts, and NO and IFN-gamma production of splenocytes was not altered by treatment with AG. However, the percentages of apoptotic splenocytes in T. gondii-infected BALB/c or C57BL/6 mice were not affected by AG treatment. These results suggest that NO modulates IFN-gamma production in T. gondii-infected C57BL/6 mice, and that NO is involved in mediating a protective response in toxoplasmosis susceptible, but not resistant, mice strain during acute infection.     

Comparative analysis of clinics,pathologies and immune responses in BALB/c and C57BL/6 mice infected with Streptobacillus moniliformis

Streptobacillus (S.) moniliformis is a rat-associated zoonotic pathogen that occasionally causes disease in other species. We investigated the working hypothesis that intranasal infection might lead to different immune responses in C57BL/6 and BALB/c mice associated with distinct pathologies. This study confirmed with 75% mortality the known high susceptibility of C57BL/6 mice to Streptobacillus moniliformis infection in comparison to BALB/c mice which did not develop signs of disease. Main pathologies in C57BL/6 mice were purulent to necrotizing lymphadenitis and pneumonia. Significant seroconversion was recorded in surviving mice of both strains. Differentiation of IgG-subclasses revealed mean ratios of IgG2b to IgG1 below 0.5 in sera of all mice prior to infection and of BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1 ratio of 2.5 post infection indicating a Th1 immune response in C57BL/6 versus a Th2 response in BALB/c mice. Evaluation of different sentinel systems revealed that cultural and serological investigations of these animals might not be sufficient to detect infection. In summary, an intranasal S. moniliformis infection model in C57BL/6 mice leading to purulent to necrotizing inflammations in the lung, the lymph nodes and other organs associated with a Th1 immune response is described.     

Strain-specific effects of riboflavin supplementation on zymosan-induced peritonitis in C57BL/6J, BALB/c and CBA mice

AimsWe investigated the effects of riboflavin (vitamin B2) on the kinetics of zymosan-induced peritonitis in three strains of mice.Main methodsPeritonitis was induced in males of C57BL/6J, BALB/c and CBA mice by intraperitoneal injection of zymosan (40 mg/kg) or zymosan supplemented with riboflavin (50 mg/kg). During the first 45 min of inflammation the pain symptoms were scored. At the selected time points (4, 6, 8, 10, 24, and 30 h) the mice were sacrificed and peritoneal exudates were retrieved. Leukocytes, among them polymorphonuclear cells (PMNs) and macrophages (Mac3⁺ cells) were counted. Levels of inducible nitric oxide synthase (iNOS) were measured in cell pellets while supernatants were used for measurements of nitric oxide, cytokine/chemokines (IL-6, IL-10, MCP-1, IFNγ, TNF-α, and IL-12p70), and matrix metalloproteinase-9 (MMP-9).Key findingA riboflavin ip injection induced pain symptoms itself, but reduced zymosan-induced pain in C57BL/6J and CBA strains of mice when coinjected with zymosan. In comparison with the mice injected with zymosan only, riboflavin coinjection prolonged inflammation in C57BL/6J mice due to prolonged macrophage accumulation; inhibited peritoneal leukocytes (PTL) accumulation in BALB/c due to inhibited influx of macrophages and PMNs; and inhibited PTL accumulation in CBA mice due to delayed PMN influx. These effects corresponded with the delayed (C57BL/6J) or inhibited (BALB/c and CBA) expression of iNOS in PTL lysates, and with the prolonged (C57BL/6) or inhibited (BALB/c) intraperitoneal accumulation of MMP-9. Moreover, cytokine accumulation was affected in a strain-specific way.SignificanceRiboflavin is antinociceptive during yeast-induced peritonitis, but its anti-inflammatory effects are strain-specific.     

The determination of the parameters of anxiety in C57BL/6J, CBA/Lac and BALB/c mice under the influence of a serotonin C1A receptor agonist [correction of antagonist

Three strains of inbred mice, C57BL/6J (C57), CBA/Lac (CBA), and BALB/c (BALB) were examined in the elevated plus-maze after the injection of an anxiotropic drug, a 5-HT1A agonist ipsapirone (3 mg/kg; i.p.; 30 min). Treatment with ipsapirone had different anxiogenic effects on the behavior of mice in accordance with their genotype. In C57 mice the drug produced a significant decrease in the percentage of the open-arm time and the number of open-arm entries as well as in the number of full entries (when an animal was between the half and the end of an open-arm) and in the number of head dippings. Besides; the number of C57 mice which performed full entries after the ipsapirone injection decreased. In CBA mice ipsapirone reduced the number of enclosed-arm entries, the number of the passages from one enclosed arm to another and the number of head dippings. Only the number of passages dropped in BALB mice after the drug injection. Probably, just these parameters reflect anxiety in mice of the genotypes under study. It was suggested that the sensitivity of 5-HT1A receptors in C57 mice is the highest.     

Differences in interleukin-12 and -15 production by dendritic cells at the early stage of Listeria monocytogenes infection between BALB/c and C57 BL/6 mice

The mechanisms responsible for the resistance of C57BL/6 mice and for the susceptibility of BALB/c mice to infection with Listeria monocytogenes were studied by comparing early IL-12 and IL-15 production by dendritic cells (DC) after infection with L. monocytogenes. Splenic DC expressing CD11b(low) and CD11c(+) obtained from C57BL/6 mice at 3 and 6 h after L. monocytogenes infection expressed higher levels of IL-12 p40 mRNA and IL-12 p40 protein than did those from BALB/c mice. Concurrently, a larger amount of IFN-gamma was produced by the splenic T cells from C57BL/6 mice in response to immobilized anti-TCRalphabeta mAb than by those from BALB/c mice, while the splenic T cells from BALB/c mice produced a higher level of IL-4 upon TCR alphabeta stimulation than did those of C57BL/6 mice. IL-15 mRNA and intracellular IL-15 protein were detected more abundantly in the DC from C57BL/6 mice than in those from BALB/c mice on day 3 after infection. CD3(+) IL2Rbeta (+) cells in the spleen were increased in C57BL/6 mice but not in BALB/c mice at the early stage after infection. Furthermore, IL-12Rbeta2 gene expression was up-regulated in T cells from C57BL/6 mice but not in those from BALB/c mice at the early stage after listerial infection. These results suggest that the difference in early production of IL-12 and IL-15 by DC may at least partly underlie the difference in susceptibility to L. monocytogenes between C57BL/6 and BALB/c mice.     

Effect of Different Gentamicin Dose on the Plasticity of the Ribbon Synapses in Cochlear Inner Hair Cells of C57BL/6J Mice

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1?ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. To study effects of different doses of gentamicin on the changes of synaptic ribbons of cochlear inner hair cells (IHCs) in mice, the availability of genetic information, transgenic and knock-out animals make the C57BL/6J mouse a primary model in biomedical research. Aminoglycoside ototoxicity, however, has rarely been studied in mature mice because they are considered highly resistant to the drugs. This study presents models for gentamicin ototoxicity in adult C57BL/6J mouse strains. Five-week-old mice were injected intraperitoneally once daily with 50?C300?mg gentamicin base/kg body weight for 7?days. Higher doses of gentamicin appear to be associated with earlier hearing damage in C57BL/6J mice, although not necessarily with more severe damage. At 200?mg/kg, gentamicin appears to induce significant hearing damage while not significantly affect the animal??s general condition. Therefore, 200?mg/kg may be an ideal dose for ototoxicity modeling in C57BL/6J mice using gentamicin. In the early period of different dose of gentamicin effect, when the number of hair cells had not changed, the number changes of IHC ribbon synapses had taken place. Through the number of ribbon synapses changing, IHCs increased or decreased connections with spiral ganglion nerves (SGNs). The ribbon synapses played a compensatory role for gentamicin ototoxicity, while this effect was not sufficient to maintain the normal threshold of hearing.     

Role of natural killer cells in the modulation of primary antibody production by purine nucleosides and their analogs.

Previous results from this laboratory demonstrated that treatment of mice with the adenosine analog tubercidin (Tub) reduced natural killer (NK) cell activity while stimulating antibody production whereas the deoxyadenosine analog, 2-fluoroadenine arabinoside-5'-monophosphate (FaraAMP), produced opposite effects; i.e., it stimulated NK cell activity at doses that inhibited antibody formation (Cancer Res. 48, 4799, 1988). Since NK cells have been reported to play a suppressor role in immunoglobulin induction, it was hypothesized that the actions of Tub and FaraAMP on antibody production occurred secondary to their opposing effects on NK cells. To test this hypothesis, abilities of these nucleoside analogs to modulate primary antibody response to sheep red blood cells were evaluated in a C57BL/6 mutant mouse lacking NK cell activity (the beige mutation. C57BL/6-bg/bg). As previously found with C3H/He mice. NK cell activity was inhibited (Tub, doses 2-6 mg/kg/day for 3 days) or stimulated (FaraAMP, doses 75-250 mg/kg/day for 3 days) in heterozygous mice C57BL/6-bg/+. In support of the hypothesis, these nucleosides had no effect on primary antibody formation in the homozygous mutant mice at doses that clearly stimulated (Tub) or inhibited (FaraAMP) this immune response in heterozygous C57BL/6-bg/+ animals. This results was corroborated in C57BL/6 wild-type mice by abrogation of NK cell activity using a monoclonal antibody to the NK cell surface glycophisingolipid, ganglio-n-tetraosylceramide. We conclude that under the conditions of drug administration, modulation of primary antibody formation by Tub and FaraAMP in mice occurs indirectly via NK cells. Similar experiments using the potent ADA inhibitor, deoxycoformycin, indicated that its enhancement of primary antibody formation is independent of NK cell activity.     

An X-encoded alloantigenicity between BALB/c and C57BL/6 strains of mice

To detect minor barriers to histocompatibility that might be encoded on the X chromosome in mice, we grafted reciprocal sets of (C57BL/6xBALB/c)F1, (C57BL/6xDBA/2)F1, and (BALB/cxDBA/2)F1 mice with tail skin from the respective paternal inbred strain. Our histogenic analysis suggests that, compared with the C57BL/6 mouse strain, the BALB/c strain generates X-linked antigen loss. In contrast, we detected no X-linked histogenic differences between strains C57BL/6 and DBA/2, or DBA/2 and BALB/c. To localize this X-linked barrier to histocompatibility, we produced a panel of 25 [(BALB/cxC57BL/6)F1xC57BL/6]N2 males that were grafted with C57BL/6 skin to determine which carried the BALB/c-derived component(s) necessary for graft rejection. DNA marker analysis showed one region of overlapping BALB/c-derived X-chromosomal segments among the graft rejecters, suggesting that this antigen-loss haplotype ( H-hix(c), for histoincompatibility on the X chromosome, c haplotype) may be restricted within the DXMit55 to the Xq telomere interval (which excludes only the centromeric tip of the X). Further backcrossing of H-hix(c) to C57BL/6 resulted in fewer rejecter mice than expected by the N4 generation, suggesting that a second, unlinked locus is also involved in this X-linked alloantigenicity. The vigorous rejection of male (C57BL/6xBALB)F1 and female (B6.C- H2(d)xC57BL/6)F1 skin by (BALB/cxC57BL/6)F1 males, as well as the assessment of markers on Chromosome 17 among N2 and N4 graft-recipient males, suggests that this second locus is H2, and that H-hix(b)-encoded alloantigens require both H2(b) and H2(d)-encoded presentation molecules for efficient graft rejection.     

Comparison of urethane-induced sister-chromatid exchanges in various murine strains, and the effect of enzyme inducers

The induction of sister-chromatid exchanges (SCEs) by urethane, 150 and 300 mg/kg administered i.p., was examined in bone-marrow cells of AKR, BALB/c, C3Hf, C57BL/6J and DBA/2 male mice. In all strains, the base-line level of SCE/cell was similar, ranging from 4.3 to 8.7, and the response increased with the dose of urethane. DBA/2 mice were the most susceptible to urethane at both dose levels, with 30.6 SCE/cell after treatment with 300 mg/kg, whereas the response of the other strains was from 17.4 to 21.5 SCE/cell at the same urethane dose. Pretreatment of C57BL/6J and DBA/2 mice with phenobarbital decreased the SCE frequencies induced by urethane, 300 mg/kg, to 70%, whereas a prior administration of beta-naphthoflavone reduced SCE levels in C57BL/6J but not in DBA/2 mice.     

Performance of BALB/c and C57BL/6 mice under an incremental repeated acquisition of behavioral chains procedure

BALB/c (n = 8) and C57BL/6 (n = 11) male mice were trained under an incremental repeated acquisition (IRA) procedure using two distinct training procedures: forward and backward chaining. A new metric for assessing progress on the IRA procedure, progress quotient (PQ), quantified progress as the product of chain length and number of reinforcers earned during a session divided by the total number of reinforcers earned. BALB/c mice progressed further, had higher overall responding, earned more reinforcers, and acquired the response sequences faster than the C57BL/6 mice on both training procedures. There were only minimal effects of training procedure for either strain. The strain differences found between BALB/c and C57BL/6 mice confirm the importance of genetic background to behavior. C57BL/6 mice may be deficient in learning as compared with BALB/c mice but other contributing factors probably include overall responding, motivation, and more rapid satiation or habituation to sucrose reinforcement by the C57BL/6 mice. PQ is a sensitive and valid measure of progress for use in studies of mastery-based incremental repeated acquisition and BALB/c mice perform this challenging learning task better than do C57BL/6 mice.     

Sulfamethizole attenuates poloxamer 407-induced atherosclerotic neointima formation via inhibition of mTOR in C57BL/6 mice

Mammalian target of Rapamycin C1 (mTORC1) inhibition limits plaque progression in atherosclerosis. The present study evaluated the protective effect of sulfamethizole on poloxamer 407-induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition. Poloxamer 407 (P-407) (0.5 g/kg body weight) was administered intraperitoneally to male C57BL/6 mice every third day for 148 days to induce chronic hyperlipidemia. From Day 121 to 148, animals were additionally administered Sulfamethizole (5, 10, and 50 mg/kg, p.o.), Rapamycin (0.5 mg/kg, positive control), or vehicle (1 ml/kg). Plasma lipid levels were measured on Days 120 and 148. Upon sacrifice, histological studies were performed, and aortic tissue interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and mTOR levels were evaluated. A molecular docking study was carried out to mimic the interaction of sulfamethizole with mTOR protein. Chronic P-407 administration significantly (p < 0.001) elevated plasma lipid levels, compared with those of the normal control group. Chronic hyperlipidemia resulted in increased tunica intima thickness, collagen deposition, and IL-6, TNF-α, and mTOR levels. Treatment with Sulfamethizole attenuated these parameters significantly in a dose-dependent manner. Molecular docking studies showed a significant interaction of Sulfamethizole with mTOR. In conclusion, this study suggests that sulfamethizole significantly limits poloxamer 407-induced atherosclerotic neointima formation in C57BL/6 mice via mTOR inhibition.     

Study of the hereditary differences in the cyclic nucleotide content of the blood serum in mice after exposure to stress and administration of phenazepam

Blood plasma content of cAMP and cGMP in C57BL/6, BALB/c mice and their reciprocal F1-hybrids has been studied at rest, upon exposure to stress induced in an open field technique and phenazepam injection at a dose of 0.05 and 0.1 mg/kg. Interstrain differences in baseline content and changes of nucleotide concentration in conditions of stress have been revealed. F1-hybrids inherit initial correlation between nucleotide content and the type of cAMP changes of C57BL/6 mice and cGMP changes of BALB/c mice. Phenazepam injection to C57BL/6 and BALB/c mice was shown to produce specific shifts in blood plasma cyclic nucleotide content.     

Helicobacter pylori infection in wild-type and cytokine-deficient C57BL/6 and BALB/c mouse mutants

Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes and their cytokines are thought to play a substantial role in the control of H. pylori infection. To determine the importance of T helper (Th) cytokines and background genes we investigated the natural course of H. pylori infection in BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)-4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H. pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/-) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4 deficiency had no detectable effect on H. pylori recovery rates from either strain of mice. Our data suggest a protective role of IFN-gamma by mediating inflammation in murine H. pylori infection. In addition, our data emphasize that background genes which differ between BALB/c and C57BL/6 mice regulate the clearance of H. pylori.