Bisphenol A-induced ultrastructural changes in the testes of common marmoset.

BACKGROUND & OBJECTIVES: Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. METHODS: Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 µg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. RESULTS: Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 µg/kg BW/day groups as compared to control. INTERPRETATION & CONCLUSIONS: The observed ultrastructural changes caused by BPA in testicular morphology might be indicative of a perturbed sperm production. Considering the genetic and spermatogenic similarities of common marmoset (Callithrix jacchus) and humans, the study findings are of significance. Further studies are, however, needed to elucidate the mechanism of action.

Bone healing evaluation of nanofibrous composite scaffolds in rat calvarial defects: a comparative study.

We studied the in vivo performance of scaffolds consisting of nanofibrous poly(L-lactic acid) (P) and blend of poly(L-lactic acid/gelatin) (PG) prepared by electrospinning and further composited them with hydroxyapatite (HA) via alternate soaking method, to get poly(L-lactic acid)/hydroxyapatite (PH) and poly(L-lactic acid)/gelatin/hydroxyapatite (PGH) scaffolds respectively. The purpose of this study was to assess and compare bone regeneration potential of electrospun P, PG and electrospun-alternate soaked PH and PGH scaffolds using rat as an animal model by creating two 5 mm circular defects in calvaria. The respective scaffolds were implanted into the defects as one side implantation and both side implantation. Defects left empty served as a negative control for one side implantation and as sham control for both side implantations. The outcomes of the scaffold implantation were determined after 6 and 10 weeks by digital radiography, micro-CT, dual-energy X-ray absorptiometry (DEXA) and histological analysis. PGH scaffold regenerated maximum amount of new bone with high bone mineral density (BMD) into the defects and complete closure occurred in just 6 weeks while other scaffolds failed to close the defects completely. PGH group exhibited highest BMD value after 10 weeks. Histological findings showed abundant osteoblasts and initiation of matrix mineralization in HA containing scaffolds. Masson's trichrome staining showed collagen deposition in all scaffold groups except sham control group. Biochemical and haematological parameters were well with in normal range, indicating no infection due to scaffold implantation. These results prove PGH scaffold as a potential biomaterial for bone regenerative medicine.

In vivo biocompatibility evaluation of electrospun composite scaffolds by subcutaneous implantation in rat.

In vivo biocompatibility of nanofibrous poly-L-lactic acid (P), poly-L-lactic acid/gelatin (PG), poly-L-lactic acid/hydroxyapatite (PH), and poly-L-lactic acid/gelatin/hydroxyapatite (PGH) scaffolds, useful in regenerative medicine and drug delivery, was evaluated by subcutaneous implantation in both male and female rats (n = 5) for up to 90 days. The body weight of each animal in the study was evaluated on a weekly basis, and no significant difference was noticed. Total and differential leukocyte counts displayed no inflammatory reaction due to scaffold implantation. Gross observation and histology of necropsied vital organs exhibited normal morphology of cell types and tissue, denying any systemic adverse reaction on distal organs. Histology of subcutaneous tissue surrounding scaffolds was done to assess any local toxic effect of implants and found all scaffolds to be compatible and nontoxic. Moreover, no remnant of scaffolds was observed in any of the histological sections, suggesting all scaffolds to be biodegradable. All the results in this study confirm that nanofibrous scaffolds P, PG, PH, and PGH are biocompatible and safe for bone tissue engineering application.

Genotoxicity evaluation of asymmetric lipid polymer hybrid nanoparticles of doxycycline hydrochloride following intravenous administration.

Nanoparticles, being small (<1,000 nm) in size, provide high surface area-to-volume ratio as compared with the bulk materials which increase the concern about their potential toxicities. The present investigation was undertaken to evaluate the genotoxic potential of asymmetric lipid polymer hybrid nanoparticles of doxycycline hydrochloride (DH lipomer) following intravenous route. DH lipomer was prepared by modified nano-precipitation method as reported earlier. Doxycyline loading was found to be 20 ± 2.5 %. Average particle size of DH lipomer and blank lipomer was 512 ± 8 and 520 ± 6 nm, respectively. Micronucleus (MN) assay was performed in adult healthy Swiss mice whereas chromosomal aberration (CA) test and comet assay were performed in healthy Holtzman rats following intravenous administration. Animals were divided into two sets, male and female, each set comprising of six groups (n = 5/group), viz., three test groups, blank lipomer (BL), vehicle control (VC), and positive control. Groups treated with 1.5 mg/kg BW DH lipomer did not show micronuclei formation in bone marrow cell, DNA damage, and CA, respectively, as compared with VC, suggesting no genotoxicity. On the other hand 3 and 6 mg/kg BW revealed significant (P > 0.001) increase in micronuclei formation, DNA damage, and chromosomal aberrations. Furthermore, BL (6 mg/kg BW) did not reveal genotoxic response in any of the tests, suggesting lipomer components as non-genotoxic. No sex-dependent variation in genotoxicity was observed. This study therefore suggests the potential safety of the proposed dose of DH lipomer at 1 mg/kg BW. An interesting highlight of the study is safety of lipomer matrix which could be exploited for other biomedical application.