Impact of platelet-rich plasma versus selenium in ameliorating induced toxicity in rat testis: histological, immunohistochemical, and molecular study.

This study was conducted on forty adult rats divided into four groups: Group I (control) that is divided into subgroups A, B, and C and Group II (methotrexate (MTX)-treated); the rats were injected intraperitoneally with MTX at a dose of 1 mg/kg/week, for 8 weeks. Group III (MTX-Se co-treated) was injected with MTX like Group II plus an oral administration of selenium at a dose of 10 µg/kg b.w/day, for 8 weeks. Group IV (MTX-PRP co-treated), rats were injected intraperitoneally with MTX like Group II plus platelet-rich plasma (PRP) injection under the scrotum, three times with 2-week intervals (volume-0.1 ml per injection) and euthanized after 8 weeks. Histological, immunohistochemical, and genetic expression using qPCR and western blotting technique were conducted. There was improvement in histological structure of testes in most specimens of Group IV. The latter group revealed a significant decrease in Bax and an increase in Bcl-2. The regeneration of testicular tissue was more observed in Group IV as measured by an increase in mean number of PCNA. Moreover, Group IV revealed an increased genetic level of FSCN3, GCNF, UBQLN3, and DAZL. Both MTX-Se and MTX-PRP have an anti-inflammatory effect as measured by a reduction in NF-κb. The anti-oxidative effect of selenium and PRP was noticed by a decrease in the level of the iNos and an increase in eNos protein and the autophagy marker LC3. PRP has ameliorative effects on induced rat testicular toxicity as evaluated by morphological changes and confirmed by immunohistochemical reactions, genetic expression, and western blotting analyses including oxidative and anti- oxidative markers.

Chronic Caffeine Consumption, Alone or Combined with Agomelatine or Quetiapine, Reduces the Maximum EEG Peak, As Linked to Cortical Neurodegeneration, Ovarian Estrogen Receptor Alpha, and Melatonin Receptor 2.

RATIONALE: Evidence of the effects of chronic caffeine (CAFF)-containing beverages, alone or in combination with agomelatine (AGO) or quetiapine (QUET), on electroencephalography (EEG), which is relevant to cognition, epileptogenesis, and ovarian function, remains lacking. Estrogenic, adenosinergic, and melatonergic signaling is possibly linked to the dynamics of these substances. OBJECTIVES: The brain and ovarian effects of CAFF were compared with those of AGO + CAFF and QUET + CAFF. The implications of estrogenic, adenosinergic, and melatonergic signaling and the brain-ovarian crosstalk were investigated. METHODS: Adult female rats were administered AGO (10 mg/kg), QUET (10 mg/kg), CAFF, AGO + CAFF, or QUET + CAFF, once daily for 8 weeks. EEG, estrous cycle progression, and microstructure of the brain and ovaries were examined. Brain and ovarian 17ß-estradiol (E2), antimullerian hormone (AMH), estrogen receptor alpha (E2Rα), adenosine receptor 2A (A2AR), and melatonin receptor 2 (MT2R) were assessed. RESULTS: CAFF, alone or combined with AGO or QUET, reduced the maximum EEG peak, which was positively linked to ovarian E2Rα, negatively correlated to cortical neurodegeneration and ovarian MT2R, and associated with cystic ovaries. A large corpus luteum emerged with AGO + CAFF and QUET + CAFF, antagonizing the CAFF-mediated increased ovarian A2AR and reduced cortical E2Rα. AGO + CAFF provoked TTP delay and increased ovarian AMH, while QUET + CAFF slowed source EEG frequency to δ range and increased brain E2. CONCLUSIONS: CAFF treatment triggered brain and ovarian derangements partially antagonized with concurrent AGO or QUET administration but with no overt affection of estrus cycle progression. Estrogenic, adenosinergic, and melatonergic signaling and brain-ovarian crosstalk may explain these effects.

Quercetin Alleviates Red Bull Energy Drink-Induced Cerebral Cortex Neurotoxicity via Modulation of Nrf2 and HO-1.

The current work was aimed at evaluating the ameliorative role of quercetin (QR) on the possible toxicity of Red Bull energy drink (RB-Ed) in the cerebral cortex of rats. To achieve the goal, the rats were allocated into 4 groups. The first group received distilled water as control. Groups II and III were given Red Bull energy drink alone and in combination with quercetin, respectively. The fourth group served as recovery to group II. The experimental duration was four weeks for all groups whereas the recovery period of group IV was two weeks. QR upregulated the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes, which can protect against RB-Ed neurotoxicity. Moreover, by reducing the thiobarbituric acid reactive substance and increasing the total antioxidant capacity levels, QR protected rats' cerebral cortex against Red Bull energy drink-induced oxidative damage. Quercetin also inhibited RB-Ed-induced histomorphological degeneration which was confirmed by the increase in the intact neurons and the rise in the neuron-specific enolase immunoreaction. QR increased the reduction of the brain-derived neurotrophic factor that was elicited by RB-Ed and acts as an anti-inflammatory agent by reducing the proinflammatory marker, interleukin 1 beta and DNA damage markers, heat shock protein 70, and 8-hydroxydeoxyguanosine. It could be concluded that the alleviating impacts of QR on RB-Ed neurotoxicity in rats could be related to the modulation of Nrf2 and HO-1 which in turn affects the redox status.

Implication of JAK1/STAT3/SOCS3 Pathway in Aging of Cerebellum of Male Rat: Histological and Molecular study.

Aging causes morphological and functional changes in the cerebellum. This work aimed to demonstrate the implication of JAK1/STAT3/SOCS3 on aging-induced changes of rat cerebellum. Thirty male rats were divided into: adult (12 months), early senile (24 months) and late senile (32 months) groups. Immunohistochemical reaction of the cerebellum to GFAP and caspase-3 was assessed and the expression of JAK1, STAT3, SOCS3 proteins was also evaluated. TNFα as well as the activities of malondialdehyde (MDA) and reduced glutathione (GSH) in cerebellar tissue were also measured. The cerebellum of late senile rats revealed more degenerative changes than early senile rats in the form of increase in GFAP and caspase-3 immunoreaction. Additionally, there was decrease in JAK1and STAT3 expression in early and late senile rats and increase in SOCS3 when compare early and late senile groups with adult one. Enhancement of TNFα was noticed with aging as well as significant decrease in GSH and increase in MDA in early senile group. Moreover, late senile group revealed significant decrease in GSH and increase in MDA. It could be concluded that aging resulting in variable changes of the cerebellum as detected by morphological changes, immunohistochemical reactions of caspase-3 and GFAP and expression of JAK1/STAT3/SOCS3 proteins. Additionally, inflammatory marker TNFα and the activity of oxidative/antioxidative stress markers; malondialdehyde (MDA) and reduced glutathione (GSH) were also affected with aging.

Ameliorative effects of bone marrow derived pancreatic progenitor cells on hyperglycemia and oxidative stress in diabetic rats.

The present study aimed to investigate the effects of Bone marrow derived pancreatic progenitor cells (BM- PPCs) in diabetic rats. It was conducted on 30 adult male Sprague-Dawley rats weighing 200-220 g. They were divided into three groups: (a) Group 1 was the control group; (b) Group 2 was the diabetic (induced diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg) and (c) Group 3 was the treated (received injection of 2.5 X 106 BM- PPCs via the tail vein twice with a 21-day time interval). The blood glucose level was estimated weekly, the oxidative stress and insulin gene expression were evaluated at the end of the experiment. Pancreatic tissue histopathology was performed. The insulin immuno-histochemical reaction was applied to the islets. The blood glucose level was reduced in the treated group over time till reaching its acceptable level whereas it was increased in the diabetic group. The oxidative stress was decreased in the treated group compared to the diabetic one. The treated group showed increased expression of the insulin gene compared to the diabetic group. The immune-histochemical analysis of insulin showed an increased number and size of pancreatic islets in the treated group compared to the diabetic one. Thus, the twofold injection of BM- PPCs could restore the normal beta-cell morphology and function.

Morphological and ultrastructural changes in the placenta of the diabetic pregnant Egyptian women.

Diabetes mellitus (DM) is a chronic metabolic disease in which the body fails to produce enough insulin or increased tissue resistance to insulin. The diabetes may have profound effects on placental development and function. This study was designed to detect the placental changes in pregnancy associated with DM comparing these changes with normal placenta. The study was carried out on sixty full-term placentae; divided into three equal groups; control group (group I): placentae of normal pregnancy, uncontrolled diabetes (group II): placentae from pregnant women whose blood glucose is poorly controlled during pregnancy. Controlled diabetes (group III): includes placentae from diabetic women whose blood glucose is controlled during pregnancy. The placentae from group II tend to be heavier and exhibited immaturity of villi, villous edema, fibrosis, excessive syncytial knots formation and infarctions. In addition to, fibrinoid necrosis, increased thickness of vasculosyncytial membrane, syncytial basement membrane, microvillous abnormalities and vascular endothelial changes were demonstrated. The syncytial multivesicular knots were present in placentae of group II. The nuclei within these syncytial knots display condensed chromatin, either dispersed throughout the nucleus or in the form of dense peripheral clumps with and numerous cytoplasmic vacuoles. The syncytial basement membrane showed focal areas of increase in its thickness and irregularity. Villous cytotrophoblasts showed increased number and activity in the form of numerous secretory granules, abundant dilated RER, larger distorted mitochondria. Villous vessels showed various degrees of abnormalities in the form of endothelial cell enlargement, folding, thickening and protrusion of their luminal surfaces into vascular lumen making it narrower in caliber. In placentae of group III, most of these abnormalities decreased. In most of placentae of group III, the VSM appeared nearly normal in thickness and showed nearly normal composition of one layer of syncytiotrophoblastic cells, one layer of smooth, regular capillary endothelium and the space between them. Mild microvillous abnormalities were noted in few placentae as they appeared short and blunted with mild decrease in their number per micron. The electron picture of syncytial knots appeared nearly normal containing aggregations of small, condensed hyperchromatic nuclei, minimal vacuoles could be seen in the cytoplasm of syncytial knots. Syncytial basement membrane appeared regular and nearly normal in its thickness and composition coming in direct contact with fetal blood capillaries but mild abnormalities were noted in the basement membrane in few placentae as increased its thickness and deposition of fibers or fibrinoid. Regarding cytotrophoblasts in the terminal villi of placentae with controlled diabetes, these cells appeared nearly normal. They were scattered beneath the syncytium and were active containing mitochondria, rough endoplasmic reticulum, free ribosomes and a large nucleus with fine dispersed chromatin. The vascular ultrastructural pattern in terminal villi of placentae of this group showed no significant abnormalities and was normally distributed in the villous tree. The luminal surface of the vascular endothelium appeared regular smooth in the majority of placentae of this group. The endothelial cells appeared connected to each other with tight junctions. It could be concluded that whether if long-term diabetes is controlled or not, placentae of diabetic mother showed a variety of significant histological structural changes seen more frequently than in the placentae of pregnant women without diabetes.