Alterations In Histoarchitecture Research Articles

P-002 Acetate attenuates cyclophosphamide-induced testicular toxicity by modulating steroidogenic and apoptotic signaling via an oxidative stress-dependent pathway

Abstract Study question Will acetate therapy attenuate cyclophosphamide-induced testicular toxicity when used concomitantly? Summary answer Acetate attenuated cyclophosphamide-induced testicular toxicity by modulating steroidogenic and apoptotic signaling via an oxidative stress-dependent pathway. What is known already Cyclophosphamide is an anthracycline that is effective in the management of cancers. Nonetheless, a major drawback of this drug is its testicular toxicity. Available evidence in the literature revealed that cyclophosphamide induces testicular toxicity by targeting steroidogenesis and activating oxidative stress, inflammation, and apoptosis. On the other hand, acetate has been reported to exert antioxidant, anti-inflammatory, and anti-apoptotic activities. However, there is no report on the effect of acetate on cyclophosphamide-induced testicular toxicity. Study design, size, duration This is a prospective experimental study using animal model. Twenty-four sexually mature litter-mate male Wistar rats of comparable weight were used for the study. The study lasted 2 weeks. Participants/materials, setting, methods Animals were acclimatized for two weeks, and then randomized into four groups. The control rats received 0.5mL of distilled water p.o for 14 days, acetate-treated rats received 200 mg/kg/day of acetate p.o for 14 days, cyclophosphamide-treated rats received 150 mg/kg of cyclophosphamide i.p on day 8, while acetate + cyclophosphamide-treated rats received treatment as acetate-treated and cyclophosphamide-treated. The doses of drugs used were the Human Equivalent doses for rats and as earlier reported. Main results and the role of chance Acetate attenuated cyclophosphamide-induced alterations in testicular histoarchitecture and the rise in testicular activities of gamma glutamyl transferase and lactate dehydrogenase activities, and lactate levels. In addition, acetate abrogated cyclophosphamide-induced rise in testicular malondialdehyde, TNF-α, IL-1β, NF-kB, and Bax levels, and myeloperoxidase, caspase 9, and caspase 3 activities, which was accompanied by acetate-driven blockade of cyclophosphamide-induced decline in reduced glutathione, Nrf2, and Bcl-2 levels, and glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase activities. Furthermore, acetate alleviated cyclophosphamide-induced suppression of circulatory levels of FSH, LH, and testosterone, testicular concentrations of 3β-HSD, 17β-HSD, and testosterone, and spermatogenesis and lowered sperm quality. Limitations, reasons for caution This was an experimental study using a rat model; hence, the results of this study should be extrapolated to humans with caution. Clinical trials are recommended to validate these findings. Wider implications of the findings The present study revealed the protective effect of acetate treatment on cyclophosphamide-induced testicular toxicity. These findings provide convincing evidence of the attenuating effect of acetate in cyclophosphamide-induced testicular toxicity. Trial registration number N/A

Alterations in viscera histoarchitecture and organosomatic index as biomarkers of toxicity induced by Aba-Eku and Olusosun solid waste landfill leachates in Rattus norvegicus.

Solid waste disposal generates leachate, a mixture of deleterious chemical, physical and microbial contaminants, which poses risk to human and wildlife health. Leachate toxicity on relative organ weight and histopathology of important viscera in mammalian body is scarce. Leachate induced toxic effects on organosomatic indices and histopathology of vital mammalian organs were investigated. Wister rats were orally exposed to 1 - 25 % of raw and simulated leachates from Aba-Eku and Olusosun landfills for 30 days. At post-exposure, organosomatic index and histoarchitectural assessment of major viscera (heart, spleen, thymus and lungs) were conducted. The physico-chemical and organic compositions of the leachates were analysed using standard protocol. The tested leachates decreased weekly and terminal body weights, and altered organosomatic index of examined viscera in rats. The histoarchitecture of the investigated viscera revealed pathologies that ranged from mild to severe degeneration, cellular infiltration, haemorrhage, congestion, necrosis, disorganization of tissues and vacuolations. Others include increased histiocytes within the bronchial associated lymphoid, lymphoid depletions, haemosiderin deposits and apoptosis were observed in the examined viscera. Physico-chemical analysis of the leachates showed different concentrations of toxic metals, PAHs and PCBs that were higher than national and international permissible limits allowed in wastewaters. The physico-chemical compositions of the leachates are capable of eliciting the observed alterations in organosomatic indices and histopathological lesions in mammalian viscera. Xenobiotic components of the leachates possibly generated free radicals and/or directly disrupted the organ architectures. These findings suggest health risk to wildlife and human population exposed to emissions from waste landfills.

Chronic low-dose chromium VI exposure induces oxidative stress and apoptosis with altered expressions of DNA repair genes and promoter hypermethylation in the liver of Swiss albino mice.

The present investigation dealt with harmful effects of hexavalent chromium (Cr [VI]) on liver of Swiss albino mice. This variant exhibited cytotoxicity, mutagenicity, and carcinogenicity. Our study focused on elucidating the hepatotoxic effects of chronic low-dose exposure to Cr (VI) (2, 5, and 10ppm) administered via drinking water for 4 and 8months. The observed elevation in SGPT, ALP, and SGOT and increased oxidative stress markers unequivocally confirmed the severe disruption of liver homeostasis at these low treatment doses. Noteworthy alterations in histoarchitecture, body weight, and water intake provided further evidences of the harmful effects of Cr (VI). Production of reactive oxygen species (ROS) during metabolism led to DNA damages. Immunohistochemistry and qRT-PCR analyses revealed that chronic low-dose exposure of Cr (VI) induced apoptosis in liver tissue. Our study exhibited alterations in the expression pattern of DNA repair genes (Rad51, Mutyh, Mlh1, and Ogg1), coupled with promoter hypermethylation of Mutyh and Rad51, leading to transcriptional inhibition. Our findings underscored the potential of low-dose Cr (VI) exposure on hepatotoxicity by the intricate interplay between apoptosis induction and epigenetic alterations of DNA repair genes.

The beneficial role of combinatorial spondias mombin and metformin treatments in Streptozotocin (STZ)-induced Pancreatic damage

There is increasing folkloric evidence of the use of the Spondias mombin plant in the management of various illnesses including diabetes. This could be attributed to its anti-hyperglycemic activity. In the same manner, combinatorial therapy has been reported to give a better achievement of glycemic control. On this note, we examined the role of Spondias mombin or Metformin and their combined administrations following streptozotocin-induced hyperglycemia and pancreatic damage in Wistar rats.For this study, 10 groups of rats (80–150 g) were utilized (A-J, n = 10). 1 mL/kg of citrate buffer (i.p.) was administered to the experimental control, while Groups B through F & I received Streptozotocin (STZ 60 mg/kg, i.p.), Spondias mombin (600 mg/kg p.o.), (400 mg/kg p.o), (200 mg/kg p.o), metformin (12.5 mg/kg p.o), and Spondias mombin + metformin (12.5 mg/kg) respectively; group B (untreated) while others were treated following hyperglycemia induction. Spondias mombin (400 mg/kg) only and metformin (12.5 mg/kg) only were administered to groups G and H, while J (not-induced) received Spondias mombin + metformin (12.5 mg/kg). Treatment lasted four weeks. The pancreatic tissues were evaluated for histoarchitectural damage with the Hematoxylin and Eosin, Masson Trichome, and Periodic acid Schiff's stains. The Bcl-2 antibody was used to label the Bcl-2 protein for apoptotic changes. Data were analyzed using one-way ANOVA and mean comparisons were done with the Duncan Multiple Range post hoc test. Significant differences were set at p < 0.05.Pancreatic induction with STZ resulted in pancreatic histoarchitectural alterations while Spondias mombin treatment only and combined Spondias mombin treatments with metformin ameliorated these abnormalities. Serum insulin was significantly decreased (p < 0.05), Peritoneal fluid α-Amylase, was significantly increased (p < 0.05), and serum caspase-3 levels were significantly increased (p < 0.05) in the STZ-only treated group compared to the control. Spondias mombin, metformin only, and the Spondias mombin+metformin administered groups (C-F, and I) restored these alterations. Bcl-2 Immunoreactivity was in a dose-dependent fashion. The Combined administrations of Spondias mombin and metformin exerted beneficial effects in Streptozotocin-induced pancreatic damage.

Lead induced genotoxicity and hepatotoxicity in zebrafish (Danio rerio) at environmentally relevant concentration: Nrf2-Keap1 regulated stress response and expression of biomarker genes

Genotoxic and hepatotoxic potentials of Pb at an environmentally relevant concentration (5 ppm) in zebrafish were investigated in the present study. Erythrocytic nuclear abnormality tests revealed the increased frequencies of abnormal erythrocytes after Pb exposure, indicating a strong genotoxic potential of Pb. Multiple stress-related parameters were further evaluated in liver, the major detoxifying organ. Pb caused increased production of ROS, which in turn caused severe oxidative stress. As a result, lipid peroxidation was increased, whereas reduced glutathione level and catalase activity was decreased. Alterations in liver histoarchitecture also served as evidence of Pb-induced hepatotoxicity. Pb-induced ROS stress triggered upregulation of Nrf2, Nqo1, Ho1; downregulation of Keap1, and altered mRNA expressions of Mn-sod, Cu/Zn-sod, gpx1, cyp1a, ucp2 suggesting involvement of Nrf2-Keap1-ARE signaling in cellular defence. Nrf2-keap1 is a sensitive biomarker of Pb-induced ROS stress. Overexpression of Hsp70 and other genes in hepatocytes might help cell survival under oxidative stress generation.

In-feed antiparasitic veterinary drug emamectin benzoate impairs acetylcholinesterase activity and brain tissue histoarchitecture of Oreochromis niloticus fry

Emamectin benzoate (EB) is an antiparasitic veterinary drug in temperate aquaculture to control ectoparasites. Research on its safety, tolerability and toxicity in tropical aquaculture is growing recently. This study examined the neurological and brain histopathological effects and the accumulation of tissue residues in all-male Oreochromis niloticus fry when fed top-coated EB feeds containing doses ranging from 50 to 500 µg/kg biomass/day for 14 days. A dose-dependent increase in mortalities (3.33–13.75 %) and inhibition in acetylcholinesterase activity (43.80–83.52 %) were documented. In the50-µg group, the muscle EB-residues peaked at 2.77 ng/g and then dropped after dosetermination. Yet, traces of residues were demonstrable in the treated groups even after 21 days of cessation of EB feeding. Histologically, dose-dependent alterations like granular layer degeneration, spongiosis, necrotized areas in the stratum album centrale, stratum griserum centrale stratum griseum superficiale, and stratum marginale and stratum opticum degeneration in the brain tissues were documented. The neuron cells were scattered or degenerated and stretched with a shrunken nucleus in the treated groups. The revocable alterations in acetylcholinesterase and brain histoarchitecture upon the termination of dosing indicated that the fry can able to tolerate and mount adaptive responses to overcome the EB toxicity.

Neurobehavioral deficits, histoarchitectural alterations, parvalbumin neuronal damage and glial activation in the brain of male Wistar rat exposed to Landfill leachate

Concerns about inappropriate disposal of waste into unsanitary municipal solid waste landfills around the world have been on the increase, and this poses a public health challenge due to leachate production. The neurotoxic effect of Gwagwalada landfill leachate (GLL) was investigated in male adult Wistar rats. Rats were exposed to a 10% concentration of GLL for 21 days. The control group received tap water for the same period of the experiment. Our results showed that neurobehavior, absolute body and brain weights and brain histomorphology as well as parvalbumin interneurons were severely altered, with consequent astrogliosis and microgliosis after 21 days of administrating GLL. Specifically, there was severe loss and shrinkage of Purkinje cells, with their nucleus, and severe diffused vacuolations of the white matter tract of GLL-exposed rat brains. There was severe cell loss in the granular layer of the cerebellum resulting in a reduced thickness of the layer. Also, there was severe loss of dendritic arborization of the Purkinje cells in GLL-exposed rat brains, and damage as well as reduced populations of parvalbumin-containing fast-spiking GABAergic interneurons in various regions of the brain. In conclusion, data from the present study demonstrated the detrimental effects of Gwagwalada landfill leachate on the brain which may be implicated in neuropsychological conditions.

Erythritol attenuates testicular dysfunction in diabetic rat via suppression of oxidative stress, inflammation and apoptosis

Hyperglycemia –induced oxidative stress and inflammation have been closely associated with diabetes complications including testicular dysfunction. Conversely, reducing blood glucose and/or use of antioxidant have been associated with reduced diabetes complications. The present study investigated the effect of erythritol (which has both antioxidant and blood glucose lowering function) on diabetes –induced testicular dysfunction in rats. Thirty male Wistar rats (170–200g) were randomly divided into 5 groups: 1) control; 2) erythritol; 3) diabetic; 4) diabetic + erythritol 1000 mg/kg; and 5) diabetic + metformin 300 mg/kg. After 8 weeks of treatment period, blood sample, testes and epididymis were collected for reproductive hormones, biochemical and histological examinations, and sperm analysis respectively. There was a significant (p < 0.05) decrease in sperm count, sperm motility, sperm morphology and serum reproductive hormones (Follicle stimulating hormone (FSH), Leutinizing hormone (LH), testosterone and gonadotropin releasing hormone (GnRH)) of diabetes rat compared to control. Also, diabetes rat showed increase in sperm and testicular malonaldehyde (MDA) and decrease in sperm and testicular superoxide dismutase (SOD) activity and glutathione (GSH) level. Further, diabetes rat showed reduced testicular weight, decreased testicular 17β-HSD and 3β-HSD activity and testicular histo-architectural alteration which were accompanied by decrease testicular vascular endothelial growth factor (VEGF) and concomitant increase in testicular myeloperoxidase activity and level of caspase 3. The present results indicates that induction of diabetes in rat causes reduction in the level of reproductive hormones (Testosterone, LH and FSH) as well as sperm and testicular oxidative stress causing abnormal sperm parameters, and biochemical and histo-architectural alterations in the testes of rats. In addition, the present results suggest that erythritol administration reduced blood glucose and ameliorated hyperglycemia –induced oxidative stress –mediated alterations in both sperm and testes of diabetes rat. Further, the present study suggests that erythritol improved testicular oxidative stress, inflammation and apoptosis by up-regulating VEGF.

Modulation of cigarette smoke induced alterations by aqueous Ocimum sanctum leaf extract in pulmonary tissue of rodents

Smoking has been associated with an increased risk of asthma, lung cancer, cardiovascular diseases, chronic bronchitis, and a massive amount of oxidative stress. The present study was undertaken to determine the modulatory effects of Holi Basil/Tulsi, (Ocimum sanctum) leaf extract on cigarette smoke-induced pulmonary damage in mice. Cigarette smoke (CS) inhalation increased the levels of pulmonary lipid peroxidation, and reactive oxygen species and decreased the levels of glutathione. Histoarchitectural alterations and enhanced tissue lactate dehydrogenase (LDH) activity in pulmonary tissue was distinctly indicative of damage. Enhanced mucin production was also observed through mucicarmine and Alcian Blue-Periodic Acid Schiff (PAS) staining. Increased expression of MUC5AC was also observed. Alterations in the lung were also evident through FTIR studies. Administration of Ocimum sanctum leaf extract (80 mg/kg b.w) to CS exposed mice ameliorated these alterations to a greater extent. These findings are suggestive of the fact that Ocimum sanctum leaf extract effectively modulated CS-induced deleterious effects on pulmonary tissue.

Remodeling in early myocardial infarction: alteration of extracellular matrix; Collagen-1, Collagen-3, α-SMA, and α-Actinin in Porcine heart model

Link of Video Abstract: https://youtu.be/lThOW40upEc Background: Myocardial infarction (MI) leads to remodeling due to altered cardiac structure and function. The study of MI histopathology in humans or large animals mimicking the human heart is limited. Using the porcine heart model, our study investigated the composition of myocardial extracellular matrix (ECM) in collagen-1, collagen-3, α-smooth muscle actin (α-SMA), and α-actinin before and after myocardial infarction. Methods: This study used two groups of domestic pigs: the Infarct group (n=4) and the Sham group (n=4). MI was induced by permanent ligation of the proximal branch of the posterior left ventricular artery. Cardiac enzymes, electrocardiography, and echocardiography data were collected before and after ligation. Cardiac tissue was harvested from the infarcted area after 60 minutes of ligation and stained with hematoxylin-eosin and Movat's Pentachrome. Collagen-1, collagen-3, and α-SMA were identified with immunohistochemical labeling, and the labeled area was measured using ImageJ. Meanwhile, α-actinin was visualized using immunofluorescence. Results: Expression of collagen-1, collagen-3, and α-SMA in the infarct group were significantly decreased after 60 minutes of infarction compared with those in the sham group (p&lt;0.01). The α-actinin was fragmented and diminished in the infarct group. Conclusion: Myocardial remodeling was detected 60 minutes after infarction with mild alteration in myocardial histoarchitecture and significant deterioration of ECM composition of collagen-1, collagen-3, α-SMA, and fragmented α-actinin fibers in the porcine heart model.

Oral administration of Nigella sativa oil attenuates arsenic-induced redox imbalance, DNA damage, metabolic distress, and histopathological alterations in rat intestine

BackgroundExposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action. MethodsRats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz KM (Michaelis-Menten constant) and Vmax of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS). ResultsNaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings. ConclusionNSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication.

The Hydrophobic Extract of Sorghum bicolor (L. Moench) Enriched in Apigenin-Protected Rats against Aflatoxin B1-Associated Hepatorenal Derangement.

Aflatoxin B1 (AFB1) is a recalcitrant metabolite produced by fungi species, and due to its intoxications in animals and humans, it has been classified as a Group 1 carcinogen in humans. Preserving food products with Sorghum bicolor sheath can minimise the contamination of agricultural products and avert ill health occasioned by exposure to AFB1. The current study investigated the ameliorating effect of Sorghum bicolor sheath hydrophobic extract (SBE-HP) enriched in Apigenin (API) on the hepatorenal tissues of rats exposed to AFB1. The SBE-HP was characterised using TLC and LC-MS and was found to be enriched in Apigenin and its methylated analogues. The study used adult male rats divided into four experimental cohorts co-treated with AFB1 (50 µg/kg) and SBE-HP (5 and 10 mg/kg) for 28 days. Biochemical, enzyme-linked immunosorbent assays (ELISA) and histological staining were used to examine biomarkers of hepatorenal function, oxidative status, inflammation and apoptosis, and hepatorenal tissue histo-architectural alterations. Data were analysed using GraphPad Prism 8.3.0, an independent t-test, and a one-way analysis of variance. Co-treatment with SBE-HP ameliorated an upsurge in the biomarkers of hepatorenal functionality in the sera of rats, reduced the alterations in redox balance, resolved inflammation, inhibited apoptosis, and preserved the histological features of the liver and kidney of rats exposed to AFB1. SBE-HP-containing API is an excellent antioxidant regiment. It can amply prevent the induction of oxidative stress, inflammation, and apoptosis in the hepatorenal system of rats. Therefore, supplementing animal feeds and human foods with SBE-HP enriched in Apigenin may reduce the burden of AFB1 intoxication in developing countries with a shortage of effective antifungal agents.

Acute Toxicity Effect of Crude Leaves Extract of Thevetia peruviana on Full Blood Count and some Organs of Clarias gariepinus Juveniles

Background: Many toxicity studies have shown that heamatological and histological alterations are widely used as good bioindicators in determining the effect of toxicants on fish. This study investigated the acute toxicity effects of the leaf extract of Thevetia peruviana on full blood count parameters and some organs of Clarias gariepinus juveniles”. Methods: One hundred and twenty C. gariepinus mixed sex juveniles were exposed to acute con-centrations (0.63, 1.25, 2.50, 5.00, and 10.00g/L ) of leave extract of T. peruviana in twelve 20 L capacity rectangular glass tanks with six treatments and bi-replicated. Blood for full blood count was collected through cardiac puncture while gills and liver were excised and analyzed for histo-pathological alterations. Results: PCV, RBC, Hb, Neu, and Lym of C. gariepinus juveniles inversely decreased while WBC directly increased with acute concentrations of T. peruviana leaves extract. The microscopic examination of the gills revealed concentration-dependent histo-architectural alterations expressed as epical clubbing, haemorrhage, desquamation, atrophy, and complete erosion of secondary lamel-lae. The liver showed moderate to severe concentration-dependent histopathological lesions typi-fied by hypertrophy, atrophy, necrosis, kupffer cell proliferation, and hepatocellular degenerations. Conclusion: Given the alterations in the blood, gills and liver noted in this study, the invasive growth of the T. peruviana plant should be controlled to minimize unwanted fish kill.

Potential of &lt;i&gt;Zingiber officinale&lt;/i&gt; Extract against Chlorpyrifos Toxicity in Caprine Testicular Cells

Chlorpyrifos, an organophosphate insecticide, is currently under studies due to its reproductive toxicity in non-targeted organisms. The present study on its efficacy as reproductive toxicant, revealed its effect on testicular cells of caprines. CPF was found to decrease cell viability in testicular cells, induced histo-architectural alterations like loss of tubular interactions and empty luminal spaces in testis; initiated DNA damage associated apoptosis as revealed by MTT, Histology and EB/AO fluorescence assay respectively, at both the doses (10 and 50 &amp;#956;M). CPF mediated toxicity induced oxidative stress in testicular cells as revealed by dose- and time-dependent increase in lipid peroxidation and decline in ferric reducing antioxidant power. However, supplementation of Zingiber officinale (ginger) extract reduced the CPF mediated decrease in cell viability, histological defects, incidence of apoptosis, and generated oxidative stress parameters; thus, proving its potential as a therapeutic agent against CPF, preventing testicular cells toxicity mediated reproductive disorders.

Appraisal of sub-chronic exposure to lambada-cyhalothrin and/or methomyl on the behavior and hepato-renal functioning in Oreochromis niloticus: Supportive role of taurine-supplemented feed

The existing study was designed to inspect the toxicological consequences of two pesticides; lambda-cyhalothrin (LCT) and methomyl (MTM) and their combination on Nile tilapia (Oreochromis niloticus) behaviors, oxidative stress, hepato-renal function indices and microarchitectural alterations. In addition, the efficiency of taurine (TUR) to rescue their toxicity was also considered. Juvenile O. niloticus were assigned into eight groups. The control and TUR groups were fed on a basal diet and TUR-enriched (10 g kg1) diet, respectively. The other groups were fed on a basal diet, and exposed to LCT (0.079 µg L–1), MTM (20.39 µg L–1 and (LCT + MTM). The last three groups were (LCT + TUR), (MTM + TUR), and (LCT + MTM + TUR) and fed on a TUR-enriched diet during exposure to LCT and/or MTM for 60 days. The exposure to LCT and/or MTM resulted in several behavioral alterations and stress via enhanced cortisol and nor-epinephrine levels. A significant elevation of serum 8-hydroxy-2- deoxyguanosine, aspartate and alanine aminotransferases, lactate dehydrogenase, Alkaline phosphatase, urea, creatinine was also observed in these groups. Furthermore, reduced antioxidant enzymes activities, including (catlase, glutathione peroxidase, and superoxide dismutase) with marked histopathological lesions in both liver and kidney tissues were detected. The up-regulated Bax and down-regulated Bcl-2 proteins were expressed in the liver and kidney tissues of LCT and/or MTM -exposed groups. Interestingly, all the observed alterations in behaviors, biochemical indices, and histo-architecture of renal and hepatic tissues were mitigated by TUR supplementation. The findings suggest that feeding O. niloticus dietary TUR may help to reduce the negative effects of LCT and/or MTM, and can also support kidney and liver health in O. niloticus, making it a promising aquaculture feed supplement.

Tocopherol Enhances the Antioxidant Defense System and Histomorphometric Parameters in The Gastrointestinal Tract of Rats Treated with Sodium Arsenite.

Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown. Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure.Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer's patches in the intestines, which are all lessened with tocopherol treatment. These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract. Keywords: Tocopherol, arsenic, stomach, ileum, colon.

Myristica Fragrans (Nutmeg) Extract Ameliorated Caffeine-Induced Cardiotoxicity in Male Wistar Rats

Caffeine is the major constituent found in coffee, tea, energy drinks, and chocolate bar among many others. Several studies have reported various effects of caffeine on the cardiovascular system, although there are inconsistencies in these findings. This study, based on these sought to investigate the role of Myristica fragrans on caffeine-induced cardiotoxicity in male Wistar rats. Twenty-five healthy Wistar rats, weighing 130-135 g were randomly assigned into groups (A-E) n=5 each. Group A received 2 mL/kg distilled water as placebo, group B was administered caffeine (40mg/kg), group C received Myristica fragrans only (200mg/kg), group D received caffeine (40mg/kg), and Myristica fragrans (100mg/kg), while group E received caffeine (40mg/kg) and Myristica fragrans (200mg/kg). The rats were orally-gavaged caffeine and Myristica fragrans with the aid of an oral cannula for 21 days. On the 22nd day after the last administration, rats were euthanized sacrificed and the heart tissues were obtained histological procedures. Percentage weight change was significantly decreased (p &lt;0.05), and Lactate dehydrogenase (LDH) activity was significantly increased (p &lt;0.05) in group B relative to the control group. The heart, relative heart weights, and cardiac troponin I were not significantly different (p=0.05) across all experimental groups relative to the control. Assessment of the cardiac histoarchitecture revealed diverse alterations in the caffeine-only group which were ameliorated by administration of 100 and 200 mg/kg Nutmeg extract in groups D and E respectively. Caffeine administration resulted in alteration in cardiac histoarchitecture with 100 and 200mg/kg Myristica fragrans ameliorating these alterations. Nutmeg could serve as a drug lead in the management of cardiac-related conditions.

Histoarchitectural Alterations in Various Tissues of Poecilia sphenops Exposed Three Sub Lethal Concentrations of Atrazine

Histoarchitectural Alterations in Various Tissues of Poecilia sphenops Exposed Three Sub Lethal Concentrations of Atrazine

Hyperactive neutrophils infiltrate vital organs of tumor bearing host and contribute to gradual systemic deterioration via upregulated NE, MPO and MMP-9 activity

Cancer is known to have systemic impact by targeting various organs that ultimately compromises the overall physiology of the host. Several reports have demonstrated the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, their role in mediating systemic effects during cancer progression has not been deciphered so far. Therefore, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern their systemic role, we evaluated neutrophil count and function at different stages of tumor growth in Dalton's Lymphoma mice model. Notably, our results displayed a gradual increase in Ly6G+ neutrophils in peripheral blood and their infiltration in vital organs including liver, lungs, spleen, kidney, lymph nodes and peritoneum of tumor bearing host. We showed remarkable alterations in histoarchitecture and serum enzyme levels that aggravated with tumor progression. We next examined neutrophil function by assessing its granular cargoes including neutrophil elastase (NE), myeloperoxidase (MPO), and matrix metalloproteinases (MMP-8 and MMP-9). Interestingly, blood neutrophils of tumor bearing mice exhibited a marked change in morphology with gradual increase in NE and MPO expression with tumor growth. In addition, we observed upregulated expression of NE, MPO, MMP-8 and MMP-9 in the vital organs of tumor bearing host. Taken together, our results demonstrate heightened infiltration and function of neutrophils in vital organs of tumor bearing host which possibly account for gradual systemic deterioration during cancer progression. Our findings thus implicate neutrophils as a potential therapeutic target that may help to reduce the overall fatality rate of cancer.

Generation and analysis of Prss28 and Prss29 deficient mice using CRISPR-Cas9 genome-editing.

Glands of the uterus are essential for the establishment of pregnancy in mice and their products regulate embryo implantation and stromal cell decidualization critical for pregnancy establishment. Forkhead box A2 (FOXA2) is expressed specifically in the glands and a critical regulator of their differentiation, development and function. Progesterone and FOXA2 regulate members of a serine proteinase gene family (Prss28 and Prss29). Here, CRISPR-Cas9 genome-editing was used to create mice with a heterozygous or homozygous deletion of Prss28 or/and Prss29 to determine their biological roles in uterine function. Female mice lacking Prss28 and Prss29 or both developed normally and were fertile without alterations in uterine histoarchitecture, uterine gland number, or and gene expression. Thus, Prss28 and Prss29 are dispensable for female fertility and do not impact endometrial gland development or uterine function mice.