Does Omeprazole, the Proton-Pump Inhibitor, Affects the Structure of the Kidney of Male Albino Rats? Histological and Laboratory Study.

Introduction: This study was done to assess the injurious effects of omeprazole by an in vivo experimental study on rat kidneys. Materials and Methods: Forty-two adult male albino rats were divided into four groups: Control group (I) in which rats were not administrated any treatment. In Groups IIa, IIb, and IIc rats received daily oral omeprazole in dose of 0.75 mg per kg for 2, 4, and 6 weeks, respectively. At the end of the experiment, blood samples were collected for serum creatinine and blood urea nitrogen measurement. Then, animals were sacrificed, and kidney specimens were processed for paraffin blocks, sectioned and stained with H and E, Mallory trichrome and Periodic acid-Schiff, then examined by the light microscope. Stained sections and image analysis were used to count vacuolated cells, pyknotic nuclei, tubular casts, and area percent of collagen fiber deposition, and then, data were subjected to the statistical analysis. Results: Examination of omeprazole-treated groups showed injury of renal corpuscles, renal tubules, and vascular congestion with inflammatory cell infiltrate in renal interstitium. Thickening of basement membrane with deposition of collagen fibers was also detected. Statistically significant increase in the number of vacuolated cells, pyknotic nuclei, hyaline casts, and area percentage of collagen fiber deposition as compared with the control group was noticed, with deterioration of renal function tests. Conclusion: It was concluded that the long-term use of omeprazole resulted in structural damage of rat renal tissue associated with deterioration of renal function in a time-dependent manner.

Does oral ciprofloxacin affect the structure of thoracic aorta in adult and senile male albino rats? A clue to fluoroquinolones-induced risk of aortic dissection.

In this study, the effect of oral ciprofloxacin on the structure of the thoracic aorta in rats was investigated. Twenty four male albino rats were divided into 4 groups (6 rats/group): group I (adult control), group II (adult rats treated with ciprofloxacin), group III (senile control), and group IV (senile rats treated with ciprofloxacin). Rats in groups II and IV received ciprofloxacin via oral gavage in a daily dose of 3.5 mg/kg/d for 14 days, while control rats received equivalent amount of distilled water used to dissolve the drug. After 2 weeks, all rats were sacrificed, thoracic aortae were dissected, and half of the specimens were processed for paraffin sections and examined by light microscopy. The other half of the specimens were prepared for scanning electron microscopy. Sections from rats treated with ciprofloxacin showed evident damaging effect on aortic wall particularly in (group IV). Aortic intima showed, focal desquamation of the lining epithelium. Tunica media exhibited loss of the normal concentric arrangement and degeneration of the smooth muscle cells. Immune staining for alpha smooth muscle actin showed muscle damage. Interestingly, some sections in (group IV) showed out-pouch (aneurysm like) of the aortic wall. There was dense collagen fibers deposition. Scanning electron microscopic observations of (group IV) revealed uneven intima, adherent blood cells and fibrin filaments to damaged intima, and out-pouch formation. It was concluded that oral ciprofloxacin caused deleterious structural changes in the thoracic aortic wall of rats explaining clinical observations of fluoroquinolones induced risk of aortic dissection and aneurysm.

The selective prostaglandin EP4 agonist, APS-999 Na, induces follicular growth and maturation in the rat ovary.

OBJECTIVE: It is known that prostaglandin E2 (PGE2) plays a crucial role in the ovulation process. PGE2 mediates its actions through four subtypes of receptors designated EP1-EP4. However, the nature of the ovulation-promoting effect of PGE2 is not well understood. We have carried out this in vivo research utilizing a new selective EP4 receptor agonist (EP4A; APS-999 Na) to investigate its role in folliculogenesis aiming at more understanding of the biological mechanism of action of PGE2. DESIGN AND METHODS: Immature, 22 day old Wistar rats were used. Animals were injected once either with placebo, 20 IU pregnant mare serum gonadotrophin (PMSG), or EP4A (10, 20 or 50 microg). In other experiments, EP4A was injected in PMSG stimulated rats. Ovarian follicle growth and development was assessed through total count and size measurement of ovulatory follicles in whole ovaries of the investigated groups. Utilizing immunohistochemistry, the spatial localization of the EP4 receptor in immature rat ovary and IL-8 pattern of expression after EP4A injection was also investigated. RESULTS: Our study showed that injection of EP4A resulted in increased follicle growth and development compared with the control, in a time- and dose-dependent manner. The highest values for follicle count and size were observed 12 and 24 h after EP4A injection. EP4A induced follicle growth with morphological characteristics similar to that induced by the standard PMSG. Most dense immune staining for EP4 receptor was noticed in proliferating granulosa cells of the secondary follicles while those of the primordial and primary follicles were not stained. EP4A injection induced the expression of IL-8 in the follicles. CONCLUSIONS: Our study revealed that: (i) the localization of EP4 receptor in the ovary implies a role in follicle growth, (ii) PGE2 induced ovarian follicle growth and development is mediated at least in part through the EP4 receptor, (iii) the action of EP4A is mediated through IL-8 up regulation and (iv) the new EP4A could be a promising reagent for various systems used to induce follicle maturation in clinical or agricultural fields. This knowledge may provide useful targets for manipulation of infertility.

Identification of mature plasma cells in early rat yolk sac. A possible origin from the endodermal cell layer: immunohistochemistry and immunoelectron microscopic study.

Plasma cells play a pivotal role in the immune system and are responsible for the synthesis and release of immunoglobulins. Numerous in vitro culture experiments on the yolk sac demonstrated the generation of mature cells of the myeloid and lymphoid lineages under appropriate culture conditions. However, there are no reports describing the development of mature lymphoid cells in the yolk sac so far. For this reason, we undertook this study to investigate the development of antibody-containing plasma cells during early yolk sac haematopoiesis. Immunohistochemistry and immunoelectron microscopy were employed in the study. Results of this work demonstrated very weak immune staining for the intracytoplasmic IgA, IgG, and IgM at days 10 and 11 of embryonic life, while dark staining was obtained at 12 days. Positive staining was localized to the endodermal cell layer. Electron microscopic examinations revealed the existence of cells with the typical characteristics of plasma cells inside the endodermal cell layer, which may suggest their endodermal origin. To further verify the nature of these cells, intracytoplasmic immunoglobulins were demonstrated by immunoelectron microscopy. The present study demonstrated emergence of mature functioning plasma cells in early rat yolk sac. In a previous work we hypothesized the possibility of endodermal origin of yolk sac macrophages. This study adds additional evidence to support that hypothesis. The possible role of plasma cells in the yolk sac is discussed.

Ontogeny of plasma cells in the early rat yolk sac.

The present study investigated the development of plasma cells in the early rat yolk sac (days 10-16 of gestation) by light microscopy, transmission electron microscopy, immunoelectron microscopy, and indirect immunofluoresce techniques. Cells delineating the morphology of plasma cells in the yolk sac were observed as early as 12 days of embryonic life. As for positive immune staining for the intra-cytoplasmic immunoglobulin (Ig) production (IgA, IgM and IgG), the intensity of the immune staining was very weak on days 10 and 11 of gestation, while it turned very dense on day 12 of gestation. At 14 days of gestation, the number of positive cells was markedly reduced. Immunoelectron microscopy visualized products of the immune reaction in cisterns of the rough endoplasmic reticulum. Conventional electron microscopic examination of 12, 13, and 16-day yolk sacs confirmed the development and differentiation of plasma cells with their well-known ultrastructural features, making this the first study to demonstrate these in the early rat yolk sac. The development of plasma cells in the early yolk sac implies the ability of the yolk sac to effect a humoral immune response at this stage of fetal life. The probable role of plasma cells in the yolk sac is also discussed.

Embryonic macrophages of early rat yolk sac: Immunohistochemistry and ultrastructure with reference to endodermal cell layer.

Macrophages are multifunctional cells that participate in numerous biological processes; they actively phagocytose foreign particles and cell debris. Embryonic tissue macrophages are present at early stages of mammalian development; their ontogeny and function is still under investigation. Our study used immunohistochemistry and electron microscopy to investigate early rat yolk sac macrophages using mouse antirat macrophage monoclonal antibodies (mAb) Mar 1 and Mar 3 produced by our laboratory. Mar 3 mAb revealed the first emergence of immature macrophages in the rat yolk sac at fetal day nine coinciding with the beginning of yolk sac haemopoiesis that consisted mainly of erythropoiesis, while Mar 1 mAb detected specifically rat yolk sac macrophages at about the 13th to 14th day of gestation. Immunoreactivity against Mar mAbs was mainly located in the yolk sac endodermal cell layer, which may signify endodermal origin of the yolk sac macrophages. Ultrastructurally mature yolk sac macrophages contained numerous endocytic vesicles or vacuoles, well-developed Golgi saccules and many electron dense granules in their cytoplasm and a number of microvillous projections from the cell surface. After establishment of the circulation between yolk sac and embryo, Mar 3 positive cells were also demonstrated inside fetal undifferentiated mesenchymal tissue at fetal day 12. The study demonstrated the first emergence of immature yolk sac macrophages being among the earliest haemopoietic cells formed in mammalian development. Thus, Mar mAbs managed to detect macrophage differentiation antigens through their development early in the rat yolk sac.