Vitamin A and Daucus carota root extract mitigate STZ-induced diabetic retinal degeneration in Wistar albino rats by modulating neurotransmission and downregulation of apoptotic pathways.

The objective of our study was to explore the deleterious effects of diabetes on the visual functions of the retina and to address whether the administration of vitamin A and carrot root extract (CE) confer retinal protection in hyperglycemic rats via modulation of oxidative stress, biochemical alternations, and retinal neurotransmission. Fifty male Wistar albino rats weighing 180 ± 12.41 g were randomized into five groups (n = 10): controls, diabetic group (injected with 40 mg/kg dissolved in 0.1 sodium citrate buffer), diabetic group treated with vitamin A (2,500 IU/kg, low dose), diabetic group treated with vitamin (5,000 IU/kg, high dose), and diabetic groups administered CE (200 mg/kg/every other day). Our findings showed that, compared to controls, diabetic rats showed a significant decrease in their retinal thickness, increased apoptotic ganglion cells, and a noticeable degeneration of their synaptic layers. The inner retina displayed increased activity of neovascularization; however, the outer retina exhibited vacuolar degeneration of the photoreceptor cell layer. Our biochemical assessments showed reduced levels of CAT, SOD, and GST along with increased lipid peroxidation. Concurrently, cellular angiogenic and stress markers were significantly elevated associated with increased apoptotic activities as evidenced by increased expressions of annexin-V and PARP. Furthermore, the neurotransmitter content of the retina was altered in diabetic rats compared to controls and diabetic-treated groups. Paradoxically, vitamin A and CE supplementation attenuate these retinal insults in diabetic animals and normalized aforementioned assayed parameters; evidencing that both treatments exerted ameliorative impacts and restored visual functions by diminishing oxidative stress and neuronal degeneration. PRACTICAL APPLICATIONS: Diabetes is a complex disease that involves various physiological perturbations especially visual functions. In our study, we showed that vitamin A and carrot root extract (CE) confer remarkable protection against retinal degeneration in STZ-induced diabetic rats. Our findings showed that the chemical and phytochemical ingredients of the vitamin A and CE substantially attenuated the histopathological changes, oxidative stress, inflammatory reactions, and cellular death in diabetic rats. These favorable changes are attributable to the high content of retinoic acid, carotenoids, and phenolic compounds that effectively regulates the production of visual pigments, increases the antioxidant defense system, and diminishes the pro-inflammatory and apoptotic pathways. Thus, the nutritional values of vitamin A and CE represent promising therapeutic choices to mitigate the retinal-induced diabetic insults.

Kaempferol Induces Cell Death in A2780 Ovarian Cancer Cells and Increases Their Sensitivity to Cisplatin by Activation of Cytotoxic Endoplasmic Reticulum-Mediated Autophagy and Inhibition of Protein Kinase B.

This study investigated whether kaempferol could inhibit ovarian cancer (OC) by activation of endoplasmic reticulum (ER) stress and autophagy, and tested its effect on the sensitivity of OC cells to cisplatin (cis-diamminedichloroplatinum, DPP). To study the effect of kaempferol on activation of ER stress and autophagy and find out whether its mechanism of action involves calcium (Ca2+), A2780 OC cells were cultured in DMEM/F12 for 24 h with or without kaempferol (40 µmol/l) in the presence or absence of autophagy or ER stress inhibitors or a calcium chelator. To study the effect of kaempferol on the sensitivity of OC cells to DPP and the potential involvement of modulation of protein kinase B (Akt) expression, A2780 OC were incubated with kaempferol and increasing concentrations of DPP (0-20 µmol/l) and then with kaempferol at its predetermined IC50 (6.8 µmol/l). Compared to control cells, kaempferol increased cell apoptosis (158 %) and decreased viability (53.17 %) and proliferation (49.17 %) of A2780 OC cells. Concomitantly, it increased the protein levels of GRP78, PERK, ATF6, IRE-1, LC3II, beclin 1, and caspase 4, thus suggesting activation of cytotoxic autophagy. This was mediated by increasing intracellular Ca+2 levels. In addition, kaempferol increased the sensitivity of A2780 cells to DPP (IC50 from 6.867 ± 0.99 to 3.73 ± 0.59 µmol/l) by decreasing the protein levels of p-Akt (0.31 ± 0.09 vs 0.12 ± 0.005). In conclusion, the findings of this study encourage the use of kaempferol alone or in combination with DPP to inhibit tumorigenesis of ovarian cells.

Visual adaptability and retinal characterization of the Egyptian fruit bat (Rousettus aegyptiacus, Pteropodidae): New insights into photoreceptors spatial distribution and melanosomal activity.

Our study was conducted to characterize the retinal structure of the Egyptian fruit bat, Rousettus aegyptiacus to determine the distribution of photoreceptors and melanosomal populations in various retinal zones. Also, we paid attention to the specific structural and functional adaptations related to their nocturnal habits. We analyzed the retinae of 12 adult male Egyptian fruit bats using morphometrical, histological, ultrastructural, and immunoblotting standard techniques. Histological findings revealed that the retinal cells have variations in geometrical architecture and different retinal thickness together with their corresponding layers bearing specific choroidal papillae projecting towards the inner retina. Immunoblotting and ultrastructure results showed that the microstructure of the retina conforms to that pattern found in mammalian species. The retinal photoreceptors are rod-dominant; alternatively, possess two spectral types of cones: SWS and LW/MWS cones as evidence for the basis for dichromatic vision. In addition, the outer retina showed densely-distributed melanin granules with a significant increase in the number of pigment epithelium cells in the eccentric retina. Furthermore, the asymmetric distribution among the retinal quadrants for the visual pigments of both rods and cones coinciding with neuronal cells such as bipolar and ganglion cells confers instructive information about their visual perception and orientation. In conclusion, our findings indicate that R. aegyptiacus efficiently discriminates colors with complex visual adaptations to mediate increased visual acuity coopted for the nocturnal niches.

Vitamin E and selenium administration synergistically mitigates ivermectin and doramectin-induced testicular dysfunction in male Wistar albino rats.

Avermectins are broad-spectrum antiparasitic drugs in veterinary and human medication. The current study aimed to examine the toxic effects of ivermectin (IVM) and doramectin (DRM), with or without co-treatment of vitamin E (Vit.E) and selenium (Se) on apoptosis, oxidative stress and male fertility in Wistar rats. Twenty five adult male animals were divided into five groups; G1; was control (CTL) received saline, G2; IVM (0.2 mg/kg b.w), G3; IVM plus Vit.E/Se (80/1.6 mg/kg b.w, respectively), G4; DRM (0.2 mg/kg b.w), and G5; DRM plus Vit.E/Se. Both IVM and DRM were given by subcutaneous (s.c) injections while Vit.E/Se was orally given. All treatments were administered once weekly for four consecutive weeks. By 24 h after the last treatment, the animals were sacrificed. Blood and tissue samples were collected for hematology, serobiochemistry, histopathology, and molecular assays for hepatic/ renal toxicities, oxidative stress, cell viability and fertility parameters. Apoptosis of the hepatic cells obtained from the treated rats was assayed by detection of annexin-V using the flow cytometric assay (FCA). The proliferating cellular nuclear antigen (PCNA) and DNA fragmentation in the treated rats' testicular tissues were also assayed. Moreover, the direct effects of IVM or DRM with or without concomitant administration of Vit.E/Se on testicular cells isolated from adult rat were also performed in vitro. Apoptosis of those cultured testicular cells in response to the different treatments was assayed by detection of the inhibition-concentration fifty (IC50) using the SRB method, and evaluating the viable versus apoptotic cells microscopically after staining with acridine orange-ethidium bromide (AO/EB). In conclusion, both avermectins induced apoptosis in the living and cultured cells, while those antioxidants; Vit.E and Se, reduced the oxidative stress and cytotoxicity both in vivo and in vitro, either. Furthermore, the reprotoxicity and reduced male fertility were seriously evoked by IVM, but not DRM with dramatic ameliorative effect of Vit.E/Se if concomitantly administered. Avermectins, especially ivermectin, should be given according to the dose recommended by the manufacturer company and repeated dosages should be given with Vit.E/Se.

Effect of both selenium and biosynthesized nanoselenium particles on cadmium-induced neurotoxicity in albino rats.

Because cadmium (Cd) is not naturally degradable by ecosystems, it interferes with many types of food chains. Cd accumulates in the kidney, liver and in the nervous tissues, especially the brain. The neurotoxicity of Cd is very high, as it alters the integrity, and increases the permeability, of the blood-brain barrier. Cd penetrates and accumulates in neurons in the brains of rats. This study reveals that Cd decreases antioxidant enzymes and increases oxidative stress in the brain. In addition, Cd increases lipid peroxidation of brain tissues. Cd increases the expression of the Cu/Zn superoxide dismutase gene. It also affects cholinergic, glutamatergic, gamma-Aminobutyric acid (GABAergic), dopamine, serotonin and acetylcholine neurotransmitters in brain tissue. Consequently, Cd increases the formation of amyloid ß, a neurotoxic index, and induces apoptosis by changing the quality and the quantity of Bcl-2, Bax and p53 proteins. In conclusion, both selenium and nanoselenium show potential antioxidant activity and promote recovery from the neurotoxic action of Cd.

Calcitriol and Punica Granatum Extract Concomitantly Attenuate Cardiomyopathy of Diabetic Mother Rats and Their Neonates via Activation of Raf/MEK/ERK Signalling and Mitigation of Apoptotic Pathways.

We investigated the detrimental effects of diabetes on myocardium of pregestational streptozotocin (STZ)-diabetic mother rats and their neonates via evaluations of oxidative redox, inflammatory and apoptotic pathways, also aiming to characterize whether calcitriol and/or pomegranate peel extract confer myocardial protection in hyperglycaemic dams and their foetuses via modulation of the Raf/MEK/ERK cascade. Sixty Sprague-Dawley female rats were randomized into five groups (N = 12): control, diabetic, diabetic treated with calcitriol and/or pomegranate peel extract (PPE), and mated with non-diabetic healthy males. After confirmation of pregnancy, treatments were kept until gestational day (E-18). Serum and cardiac tissues of mothers and foetuses were collected and processed for biochemical, histopathological, and molecular assessments. We observed that, compared to the control, diabetic mothers showed dramatically increased hyperglycaemia and hyperlipidaemia associated with decreased myocardial functions and disrupted maternal performance. Also, diabetic mothers and their neonates exhibited elevated levels of myocardial injury (troponin I, endothelin 1, creatine kinase-MB, lactate dehydrogenase), with increased pro-inflammatory cytokines (interleukin 1, interleukin 1ß, transforming growth factor ß) and oxidative redox. Concurrently, the MAPK pathway was significantly down-regulated with increased myocardial apoptotic activity. Furthermore, mRNA expression of angiogenic and fibrotic markers was significantly increased. Paradoxically, calcitriol and/or pomegranate peel extract alleviated these diabetic myocardial insults and normalized the aforementioned assayed parameters. Our findings hypothesized that calcitriol and/or pomegranate peel extract exerted cardioameliorative impacts due to their unique anti-oxidative and anti-inflammatory properties, and thus may be a promising treatment that directly targets the secondary myocardial complications of diabetes in dams and their offspring.