ABSTRACT
Background: There are few studies indicating the detrimental effects of ibuprofen on sperm fertility potential and DNA integrity
Objective: To determine the effects of Ibuprofen on sperm parameters, chromatin condensation and DNA integrity of mice
Materials and Methods: In this experimental study, 36 adult male mice with average weight 37 gr were divided into three groups, including control [group I, n=12], normal dosage of ibuprofen [group II, n=12] and high dosage [group III, n=12]. Ibuprofen with different doses was dissolved in daily water of animals. After 35, 70 and 105 days, the cauda epididymis of mice were cut and incubated in Ham's F10 media. Sperm samples were analyzed for parameters [motility, morphology and count], DNA integrity [SCD test] and chromatin condensation [chromomycin A3 and Aniline blue staining]
Results: After 35 days, in addition to above mentioned sperm parameters, all of the treated mice showed statistically significant increase in spermatozoa with immature chromatin [P<0.05]. However, after 70 days, the rate of sperm DNA fragmentation assessed by SCD was increased in group II [66.5 +/- 0.7] and the percentage of immature spermatozoa [AB[+] and CMA3[+]] was higher in group III [77.5 +/- 0.7 and 49.5 +/- 6.3 respectively] than other groups. After 105 days, the AB[+] spermatozoa were increased in both normal dose and high dose groups
Conclusion: Ibuprofen may cause a significant reduction in sperm parameters and sperm chromatin/DNA integrity in mice. It should be noted that these deleterious effects are dose-dependent and can be seen in early and late stage of drug treatments
ABSTRACT
Development of an effective vaccine is highly needed in order to restrict the AIDS pandemic. DNA vaccines initiate both arms of immunity without the potential of causing disease. HIV-1 p24 and gp41 [gag and env] proteins play important roles in viral pathogenesis and are effective candidates for immune induction and vaccine design. In this study, new DNA vaccine candidates constructed from HIV-1 fused p24- gp41 or gp41 alone were evaluated in Balb/c mice for induction of cellular and humoral immune responses. Recombinant plasmids, pcDNA3.1/Hygro expression vector containing immunogenic sequences of fused p24-gp41 or gp41alone were produced. Dendrosome used as a system for carrying vectors in laboratory animals, and an IL-12 containing vector [pCAGGS-IL-12] was co-immunized with the p24-gp41 vector as a genetic adjuvant. Induction of effective immune responses against the designed vectors as DNA vaccine candidates in Balb/c mice was evaluated. Levels of total antibodies, IgG isotypes [IgG2a and IgG1]? IFN-alpha and IL-4 were measured by ELISA. MTT assay was used to evaluate lymphoproliferation. The results confirmed that the immunogenic epitopes of both p24 and gp41 genes are highly effective inducers of immune responses, and administration of fused p24-gp41 alone or along with IL-12 resulted in further enhancement of immune responses. Group 4 that received fused fragments [p24-gp41] along with an IL-12 expressing vector demonstrated a significantly higher Stimulation Index [SI] and IFN-alpha production [p<0.0001] with a significant increase in IgG2a/IgG1 ratio, indicating the stimulation of CMI towards Th1. Although gp41 containing vector [group 6] also showed significant increases in both proliferation and IFN-alpha production, the responses were persistently lower than that of p24-gp41 containing vectors. Total antibody production was highest in group 6 as expected. Dendrosome proved to be an efficient carrier of recombinant plasmids constructed in this study. Further studies are necessary to evaluate these constructs as HIV vaccine candidates