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- SourceAvailable from: Lubhan Singh[Show abstract] [Hide abstract]
ABSTRACT: The main intention of the present study was to investigate the oxidative stress, genotoxicity and cytotoxicity of Erythromycin (EMC) in pups of treated dams in gestation as well as the lactation period. The two doses of EMC were compared by using intra-peritoneal (i.p.) route in two different periods, i.e. in gestation period and in the lactation period. The rationale behind selection of i.p. route is because of fact that EMC gets degrades in acidic pH of the stomach. The doses of EMC used were clinically equivalent dose (CED) (EMC 14.2 mg/kg, i.p.) and a lower dose (EMC 10 mg/kg, i.p.) than CED. EMC toxicities in mice pups were evaluated by using various parameters such as, micronucleus (MN) test in peripheral blood and bone marrow, Malondialdehyde (MDA) assay, Glutathione (GSH reduced) assay and histopathological assessment in liver tissue. The CED of EMC led to significant increase in MDA and decreased in GSH concentration in pups’ liver tissue in both gestation and lactation period and also significant increase in MN frequency in both peripheral blood and bone marrow cells of pups. There were no significant toxicities at a lower dose than CED. There were also some chronic findings with liver histopathological examination at CED. It is thus concluded that EMC accentuates the oxidative stress, cytotoxicity and DNA damage in pups of their post-natal life hence EMC should be avoided in the pregnancy and also in the lactation period.
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ABSTRACT: A quantitative structure-activity relationship (QSAR) and molecular docking study has been performed on a series of heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine derivatives acting as acid pump antagonists in order to have a better understanding of the mechanism of H(+)/K(+)-ATPase inhibition. The QSAR study shows a significant correlation of activity with Global Topological Charge Indices (GTCI) of the compounds and the hydrophobic constant π of some substituents, indicating that the charge transfer within the molecule and the hydrophobic property of some substituents will be the controlling factor of the activity of these compounds and that there can be dispersion interaction between the molecules and the receptor, where some substituents may have hydrophobic interaction, too. Based on this correlation some new compounds with higher potency have been predicted and their docking study has been performed to see if they can have better interaction with the receptor. The ADME properties of these predicted compounds have also been reported that follow Lipinski's rule of five.
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ABSTRACT: The antifertility effect of ampicillin (AMP, 40 mg/kg) and sulphasalazine or salicylazosulfapyridine (SASP, 300,450 and 600 mg/kg) in male rats has been reported earlier. The combination of AMP and SASP is generally used in certain pathological conditions, but the combined effect of these two drugs on the fertility is not clear. So, the aim of this study was to investigate the antifertility effect of ampicillin and sulphasalazine combination in male rats. In the present study, forty rats were randomly divided into five groups (n=8). Group I served as the control, while Group II and III received AMP and SASP at the doses of 20 mg/kg and 200 mg/kg respectively. Moreover, group IV and V received the combination of SASP (100 mg/kg) and AMP (10 mg/kg). However, for evaluating the reversible effect of the combination, a washout period of 30 days was given in group V. After 45 days of drug treatment, each rat was sacrificed. The testes, seminal vesicles and epididymis were dissected & weighed. Furthermore, fertility tests, sperm characteristic analysis, histopathological studies, testosterone assay and tissue biochemistry were performed. The data were analyzed using ANOVA and in case ANOVA shows statistical differences, post hoc analysis was performed. A decrease in parameters related to fertility of males such as sperm count, sperm motility, fertility ratio, serum testosterone level, glycogen and protein content in sexual organs was observed. Although AMP and SASP significantly (p<0.001) reduced the reproductive activity separately, but their combination was found to be impairing the reproductive activity at a considerably lower dose. However, on withdrawing the treatment, all these parameters were restored which was confirmed by the histopathological analysis of the testis. The combination produces synergistic antifertility effect in male rats and the effect was reversible. The dose and efficacy of results could be extrapolated in future clinical trials.
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