Reproductive Hormones Imbalance, Germ Cell Apoptosis, Abnormal Sperm Morphophenotypes and Ultrastructural Changes in Testis of African Giant Rats (Cricetomys gambianus) Exposed to Sodium Metavanadate Intoxication.

Environmental exposure to vanadium has been on the increase in recent time. This metal is a known toxicant. The current study was conducted to investigate the reproductive toxicity of sodium metavanadate (SMV) in male African giant rats. Administration of SMV was done intraperitoneally daily for 14 consecutive days at a dosage of 3 mg/kg body weight. Sterile water was administered to the control group. Serum reproductive hormones, sperm reserve and quality as well as testicular ultrastructural changes following SMV treatment were analysed. Results showed SMV-exposed AGR group had statistically decreased concentrations of testosterone (4.7 ng/ml), FSH (3.4 IU/L) and LH (3.8 IU/L). Also, SMV-treated group had statistically decreased sperm motility and mass activity with increased percentage of abnormal morphophenotypes of spermatozoa and upregulation of P53 immunopositive cells. Ultrastructural study revealed vacuolation of germ and Sertoli cells cytoplasm and nucleus, and mitochondrial swelling and vacuolations were also observed. There was severe disintegration of the seminiferous tubules, atrophy and degeneration of myeloid cells and apoptosis of the Leydig, Sertoli and germ cells. In conclusion, intraperitoneal SMV exposure exerts severe adverse effects on some serum reproductive hormones, reduction in the sperm reserve and quality, apoptosis and degenerative changes of the Leydig, Sertoli and germ cells which can lead to infertility.

Neuroecotoxicology: Effects of environmental heavy metal exposure on the brain of African giant rats and the contribution of vanadium to the neuropathology.

Increased exploitation of minerals has led to pollution of confined environments as documented in Nigeria Niger Delta. Information on the effects on brain of such exposure is limited. Due to its exploratory activities, the African giant rat (Cricetomys gambianus) (AGR) provides a unique model for neuroecotoxicological research to determine levels of animal and human exposure to different pollutants. This study aims to unravel neuropathological features of AGR sampled from three agro-ecological zones of Nigeria. Fifteen AGR were sampled according to previously determined data on heavy metal exposure: high vanadium, high lead, and low metals. Eighteen AGR were collected from low metal zone and divided into two groups. Control group received vehicle while SMV exposed group received 3 mg/kg sodium metavanadate (SMV) intraperitoneally for 14days. Brain immunohistochemical analyses were conducted, and ultrastructural changes were studied in experimentally exposed group. Results showed significant loss of tyrosin hydroxylase, parvalbumin, orexin-A and melanin concentration hormone containing neuronal populations in brains obtained from high vanadium and high lead zones and in experimentally intoxicated SMV groups. Similarly, significant decrease numbers of dendritic arborations; extracellular matrix density, perineuronal nets; astrocytes and microglia activations are documented in same groups. Ultrastructural studies revealed mass denudation, cilia loss, disintegration of ependymal layer and intense destructions of myelin sheaths in SMV exposed group. These are the first "neuroecotoxicological" findings in distinct neuronal cells. The implications of these findings are highly relevant for human population living in these areas, not only in Nigeria but also in similarly polluted areas elsewhere in the world.

Biochemical and ultrastructural changes in kidney and liver of African Giant Rats (Cricetomysgambianus, Waterhouse, 1840) exposed to intraperitoneal sodium metavanadate (vanadium) intoxication.

We studied the hepatic and renal impact of sodium metavanadate (SMV) exposure in African giant rats (AGR). Twelve male AGR were used and divided into two groups. The control group received sterile water while the SMV-exposed group received 3 mg/kg SMV intraperitoneally for 14 days. SMV exposed AGR groups showed significantly decreased activities of serum AST, ALT, ALP and creatinine concentration but increased blood urea nitrogen (BUN), albumin and globulin concentrations. Kidney ultrastructure examination revealed atrophy of the glomerular tuft, loss of podocytes, distortions of the endothelium and glomerular basement membrane. The liver sinusoids fenestration phenotypes were abnormal. Hepatocytes exhibited hypertrophy with uneven, crenated and dentate nuclei. SMV exposure induced activation of monocytes, as well as Kupffer and fibrous cells. Alterations in glomerular podocytes and cell-cell and cell matrix contact and inflammatory liver fibrosis are key events in progressive glomerular failure and hepatic damage due to SMV intoxication.

Ultrastructural effects of silicone oil on the clear crystalline lens of the human eye.

PURPOSE: To evaluate light and electron microscopic changes of the anterior capsule and its epithelium after clear lens extraction of vitrectomized myopic eyes with silicone oil tamponade. METHODS: This prospective, controlled, non-randomized, interventional study included 20 anterior lens capsular specimens that were excised during combined clear lens extraction and silicone oil removal from previously vitrectomized highly myopic patients with silicone oil tamponade for previous retinal detachment surgeries. The specimens were examined via light microscopy and electron microscopy and compared with 20 anterior capsule specimens removed during clear lens extraction of non-vitrectomized highly myopic eyes. RESULTS: Light microscopic examination of clear lens anterior capsule specimens of vitrectomized myopic eyes filled with silicone oil showed relatively more flat cells with irregular outline of lens' epithelial cells with wide intercellular spaces, deeply stained nuclei, and multiple intracytoplasmic vacuoles. Scanning electron microscopy revealed collagenous surfaces filled with multiple pits, depressions, and abnormal deposits. Transmission electron microscopy revealed lens epithelial cells with apoptotic changes, many cytoplasmic vacuoles, and filopodia-like protrusions between lens epithelial cells and the capsule. Epithelial proliferation and multilayering were also observed. CONCLUSION: silicone oil may play a role in the development of apoptotic and histopathological changes in clear lens epithelial cells. Clarity of the lens at the time of silicone oil removal does not indicate an absence of cataractous changes. We found justification of combined clear lens extraction and silicone oil removal or combined phacovitrectomy when silicone oil injection is planned, but further long-term studies with larger patient groups are required.

Scanning and transmission electron microscopy of the cells forming the hepatic sinusoidal wall of rat in acetaminophen and Escherichia coli endotoxin-induced hepatotoxicity.

Drugs and xenobiotics as well as bacterial endotoxins may reach the liver either systematically or after intestinal absorption. Therefore, cells lining the sinusoidal wall form the last barrier before blood constituents get in contact with the parenchymal cells. In this work, the ultrastructure of the cells forming the sinusoidal wall was studied after acetaminophen and Escherichia coli endotoxin treatments. Rats received acetaminophen at a dose of 1000 mg/kg body weight by intraperitoneal injection once in acute and four times with a 1-week interval in chronic treatments, and E. coli endotoxin at a dose of 5 mg/kg of body weight by intraperitoneal injection once in acute and four times with a 1-week interval in chronic treatments. Tissue samples were collected for scanning and transmission electron microscopy. Swelling of sinusoidal endothelial cells was noticed in both acute intoxicated groups with narrowing of the fenestrae, whereas large gaps were formed in chronic toxicity. Activation of Kupffer cells was a prominent common feature between the four toxicity groups. Interestingly, hepatic stellate cell activation was evident in both chronic acetaminophen and chronic endotoxin groups. Large amounts of collagen fibers were seen surrounding the hepatic stellate cells and in Disse space.

Immunomodulatory effect of gelatin-coated silver nanoparticles in mice: Ultrastructural evaluation.

Silver nanoparticles (SNP) are used in many pharmaceutical, cosmetic, and industrial products already available in the market. Although they are considered relatively safe, many toxic and pathological alterations in different organs including immune organs were reported after SNP administration. In this study, 10-week-old male mice (n = 20) were divided into two groups. Ten mice received greenly synthesized gelatin-coated silver nanoparticles in a dose of 10 mg/kg body weight for five consecutive days while the other 10 received 0.5 ml of distilled water daily for 5 days and kept as control. At the sixth day, all mice were sacrificed; blood and tissue samples were collected and prepared for pathological analysis. Liver and kidney lesions were in the form of degenerative and inflammatory changes. Interestingly, the immune organs were drastically affected by SNP treatment. Severe hyperplasia of the Peyer's patches was noticed in the intestines of intoxicated animals both in gross and microscopic examination. Spleen was enlarged and showed large number of megakaryocytes. The particles were encountered in membrane-bound phagosomes inside macrophages in different organs like lungs and spleen. Blood picture complied to morphological findings with an increase in monocytes and eosinophils accompanied by drop in the platelets count in the intoxicated animals.

The ameliorative effect of propolis against methoxychlor induced ovarian toxicity in rat.

A study was designed to evaluate ameliorative effect of propolis against methoxychlor (MXC) induced ovarian toxicity in rat. The organochlorine pesticide (MXC) is a known endocrine disruptor with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether chronic exposure to MXC could cause ovarian dysfunction, two groups of Sprague-Dawley adult female rats were exposed to MXC alone in a dose of 200mg/kg, twice/weekly, orally or MXC dose as previous plus propolis in a dose of 200mg/l/day, in drinking water for 10 months. Another two groups of rat were given corn oil (control) or propolis. Multiple reproductive parameters, ovarian weight, serum hormone levels, ovarian oxidative status and ovarian morphology were examined. In MXC-exposed group, there is a significant decrease in body and ovarian weight vs. control. MXC decreases serum estradiol and progesterone levels. A significant increase in the levels of lipid peroxidation was obtained while a significant decrease of the total antioxidant was recorded. Ovarian histopathology showed primary, secondary and vesicular follicles displaying an atretic morphology. Increase in the ovarian surface epithelium height accompanied with vacuolated, pyknotic oocytes were obtained. The previous toxic effects were neutralized by the administration of propolis in MXC+propolis group. The present results suggest that propolis may be effective in decreasing of MXC-induced ovarian toxicity in rat.

Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat.

The oxidative status and the morphological changes of liver of rats exposed to cadmium (5 mg Cd/kg body weight subcutaneously) for 22 days and the protective role of melatonin (10mg/kg b.w.) against the toxicity of cadmium was studied. The concentration of malondialdehyde (MDA), as an indicator of lipid peroxidation, activity of the antioxidant enzyme superoxide dismutase (SOD) as well as the concentration of glutathione (GSH) was measured in the liver. The morphological changes were investigated using both light and electron microscopes. The exposure to Cd led to an increase of MDA levels and a decrease of both the activity of SOD and GSH concentration in the liver. In contrast, melatonin administration restored the previous changes to nearly the normal levels. Morphologically, Cd led to different histopathological changes such as loss of normal architecture of the parenchymatous tissue, cytoplasmic vacuolization, cellular degeneration and necrosis, congested blood vessels, destructed cristae mitochondria, fat globules, severe glycogen depletion, lipofuscin pigments, and collagenous fibers formation. Again, melatonin administration counteracts all changes and the tissue appears more or less normal. The rate of recovery was faster when melatonin was administered for treatment after the exposure to cadmium than if the animals left without any treatment. The results suggest that melatonin may be useful as an antioxidant in combating free radical-induced oxidative stress and tissue injury that is a result of cadmium toxicity.

A novel therapeutic drug (copper nicotinic acid complex) for non-alcoholic fatty liver.

BACKGROUND: Fatty liver is the accumulation of fat in liver cells, which leads to disruption of the normal liver structure and function. METHODS: A non-alcoholic fatty liver rat model received copper (Cu) (I)-nicotinate complex [CuCl(HNA)2] for 4 weeks. RESULTS: Clinical signs and histopathological examinations showed obvious improvements in rats that received Cu complex who were continuously on an (HCFF) diet than those returned to standard diet with Cu complex. The improvement was matched in total lipids in sera and hepatic tissue, with disappearance of fat droplets from liver sections. Furthermore, the gain in body weight and the corresponding decrease in liver weight, decreased liver transaminases and alkaline phosphatase were prominent. The oxidative stress markers such as nitric oxide, lipid peroxides, glutathione and superoxide dismutase were obviously changed to healthy normal levels. CONCLUSION: The Cu complex may serve as a novel chemical restoring agent in fatty degenerated liver cells and for renewal of their structure and functions. However, clinical trials are required for more evaluation of the Cu complex in humans.