Association of Polymorphisms in PD-1 and LAG-3 Genes with Acute Myeloid Leukemia.

Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This study aims to explore the correlation between specific genetic variations (SNPs) in the PDCD1 (rs2227981) and LAG3 (rs12313899) genes and the likelihood of developing AML in the Saudi population. Material and methods: total of 98 Saudi AML patients and 131 healthy controls were genotyped for the PDCD1 rs2227981 and LAG3 rs12313899 polymorphisms using TaqMan genotyping assays. A logistic regression analysis was conducted to evaluate the relationship between the SNPs and AML risk using several genetic models. Results: The results revealed a significant association between the PDCD1 rs2227981 polymorphism and increased AML risk. In AML patients, the frequency of the G allele was considerably greater than in healthy controls (OR = 1.93, 95% CI: 1.31-2.81, p = 0.00080). The GG and AG genotypes were associated with a very high risk of developing AML (p < 0.0001). In contrast, no significant association was observed between the LAG3 rs12313899 polymorphism and AML risk in the studied population. In silico analysis of gene expression profiles from public databases suggested the potential impact of PDCD1 expression levels on the overall survival of AML patients. Conclusions: This study provides evidence for the association of the PDCD1 rs2227981 polymorphism with an increased risk for AML in the Saudi population.

Phytochemical, Antioxidant Activity, and Toxicity of Wild Medicinal Plant of Melitotus albus Extracts, In Vitro and In Silico Approaches.

Morocco is known for its high plant biodiversity, but many plants are poorly valorized. For this reason, this study aims to valorize the methanolic and aqueous extracts of Melitotus albus leaves by studying their antioxidant activity and toxicity. The extracts' antioxidant activity is assessed using the FRAP, DPPH, CAT, and ABTS methods. The chemical composition was determined using LC-MS analysis and evaluated using in silico studies. The results revealed that the total polyphenol content of the aqueous extract, 259.26 ± 7.79 (mg GAE/g), is higher than that of the methanolic extract, 131.41 ± 12.64 (mg GAE/g). The antioxidant activity by the methods of DPPH, ABTS, and phosphor molybdenum of aqueous extracts (0.087 ± 0.015, 0.014 ± 0.001 and 6.157 ± 1.050 mg eq vit C/g, respectively) is greater than that of methanolic extracts (0.107 ± 0.02, 0.167 ± 0.03, and 0.453 ± 0.014 mg eq vit C/g, respectively). The reducing power of iron (FRAP) shows that the methanolic extract has a greater reducing power than that of the aqueous extract with a low IC50 (0.011 ± 0.003 and 0.199 ± 0.016 mg/mL, respectively). The study of acute and subacute toxicity shows that the administration of the aqueous extract of M. albus at different doses increases the body weight of rats without modifying their general behavior. The M. albus extract had a 99.99% total phenolic content, as determined by LC-MS, consisting of 12 different components. The primary constituents of the extract are chlorogenic acid (43.68%), catechin/epicatechin (24.82%), quercetin-3-O-glucuronic acid (9.91%), naringin (7.64%), and p-hydroxybenzoic/salicylic acid (2.95%). The in-silico study showed that these compounds can passively permeate through the blood and have a beneficial effect on various organs of the body. Based on these results, M. albus can be used as a medicinal plant in phytotherapy, cosmetics, or as a dietary supplement. The bioactive compounds of these plants will require a lot of further effort in terms of isolation and characterization.

TIM3 and CTLA4 immune checkpoint polymorphisms are associated with acute myeloid leukemia in Saudi Arabia.

BACKGROUND: Immune checkpoints are receptors on the surface of T cells that function crucially in suppressing the immune response, and they are implicated in autoimmunity and cancer diseases. AIM: The present study aimed to investigate the relationship between functional single nucleotide polymorphisms (SNPs) of two immune checkpoint molecules, CTLA-4 and TIM-3, and acute myeloid leukemia (AML) in a Saudi population. METHODS: Two SNPs in CTLA-4 (rs231775, A > G) and TIM-3 (rs10515746, A > C) were genotyped in 229 subjects, including 98 patients and 131 healthy controls, from the Saudi population using TaqMan assay methods. Differential expression of these two genes was performed using in silico analysis. RESULTS: An association was found between polymorphisms in TIM-3 (OR: 6.01; 95% CI: 3.99-9.05, P < 0.0001) and the risk of AML. Inversely, the rs231775 SNP in the CTLA-4 gene was found to protect against AML in allelic, dominant, and additive models (P < 0.05). A significantly higher expression of TIM-3 in the blood of individuals with AML was observed. CONCLUSION: This is the first study focusing on single nucleotide polymorphisms (SNPs) for CTLA-4 and TIM-3 in acute myeloid leukemia patients in a Saudi community and could be a potential new prognostic factor for this disease.

Silver Nanoparticles Decorated with Curcumin Enhance the Efficacy of Metformin in Diabetic Rats via Suppression of Hepatotoxicity.

Hepatotoxicity is one of the significant side effects of chronic diabetes mellitus (DM) besides nephrotoxicity and pancreatitis. The management of this disease is much dependent on the restoration of the liver to its maximum functionality, as it is the central metabolic organ that gets severely affected during chronic diabetes. The present study investigates if the silver nanoparticles decorated with curcumin (AgNP-Cur) can enhance the efficacy of metformin (a conventional antidiabetic drug) by countering the drug-induced hepatoxicity. Swiss albino rats were categorized into six treatment groups (n = 6): control (group I without any treatment), the remaining five groups (group II, IV, V, VI) were DM-induced by streptozocin. Group II was untreated diabetic positive control, whereas groups III was administered with AgNP-cur (5 mg/kg). Diabetic group IV treated with metformin while V and VI were treated with metformin in a combination of the two doses of NPs (5 and 10 mg/kg) according to the treatment schedule. Biochemical and histological analysis of blood and liver samples were conducted after the treatment. The groups V and VI treated with the combination exhibited remarkable improvement in fasting glucose, lipid profile (HDL and cholesterol), liver function tests (AST, ALT), toxicity markers (GGT, GST and LDH), and redox markers (GSH, MDA and CAT) in comparison to group II in most of the parameters. Histological evaluation and comet assay further consolidate these biochemical results, pleading the restoration of the cellular structure of the target tissues and their nuclear DNA. Therefore, the present study shows that the NPs can enhance the anti-diabetic action by suppression of the drug-mediated hepatoxicity via relieving from oxidative stress, toxic burden and inflammation.

Protective Effect of Daidzein against Diethylnitrosamine/Carbon Tetrachloride-Induced Hepatocellular Carcinoma in Male Rats.

Hepatocellular carcinoma (HCC) is the second-largest cause of death among all cancer types. Many drugs have been used to treat the disease for a long time but have been mostly discontinued because of their side effects or the development of resistance in the patients with HCC. The administration of DZ orally is a great focus to address the clinical crisis. Daidzein (DZ) is a prominent isoflavone polyphenolic chemical found in soybeans and other leguminous plants. It has various pharmacological effects, including anti-inflammatory, antihemolytic, and antioxidant. This present study investigates the protective effect of DZ on chemically induced HCC in rat models. The DZ was administered orally four weeks before HCC induction and continued during treatment. Our study included four treatment groups: control (group 1, without any treatment), HCC-induced rats (group II), an HCC group treated with DZ at 20 mg/kg (group III), and an HCC group treated with DZ at 40 mg/kg (group IV). HCC rats showed elevation in all the HCC markers (AFP, GPC3, and VEGF), liver function markers (ALP, ALT, and AST), inflammatory markers (IL-6, TNF-α, and CRP), and lipid markers concomitant with a decrease in antioxidant enzymes and protein. However, groups III and IV demonstrated dose-dependent alleviation in the previous parameters resulting from HCC. In addition, the high dose of DZ reduces many hepatological changes in HCC rats. All study parameters improved with DZ administration. Due to its antioxidant and anti-inflammatory characteristics, DZ is a promising HCC treatment option for clinical use.

Pharmacological Effects of Grape Leaf Extract Reduce Eimeriosis-Induced Inflammation, Oxidative Status Change, and Goblet Cell Response in the Jejunum of Mice.

Coccidiosis is a parasitic infection threatening poultry products globally. Parasite resistance to drugs is one of the barriers to Eimeria control. Natural products are one of the sources of compounds that prevent parasite infections. The current study was, therefore, conducted to evaluate the effect of Vitis vinifera leaf extract on anti-inflammatory response, oxidative status, and goblet cell response against Eimeria papillate infection in mice. Methanol was used as a solvent for phytochemicals. The mice were divided into six groups: The first group was the control. The second group was uninfected and treated with 200 mg/kg of extract to test toxicity, and the third, fourth, fifth, and sixth groups of mice received 1 × 103 sporulated E. papillate oocysts. The third group received no treatment. The fourth and fifth groups were treated daily with 100 and 200 mg/kg of V. vinifera leaf extract, respectively, while the sixth group received 25 mg/kg of toltrazuril daily via gavage. On day 5 p.i., the animals were sacrificed, and jejunum samples were prepared for analyses of histological sections and oxidative stress. The phytochemical analysis using GC-MS of the extract showed the presence of 12 biologically active compounds. The most effective dose was 200 mg/kg, which significantly decreased the number of parasitic stages in the jejunal sections of the mice. The findings demonstrate that E. papillate infection in mice results in significant histopathological changes in the jejunum, including inflammation, epithelial vacuolation, villi loss, and a decrease in goblet cell density. When infected mice received treatment, the histological injury score within the infected jejunum tissue decreased by 63%, and the goblet cell quantity dramatically increased, approaching the control values. Finally, the extract ameliorated the changes in glutathione and malondialdehyde due to E. papillate infection. The extract was proven to have anti-inflammatory properties and reduce the number of oocysts. Overall, the findings show that V. vinifera leaf extract has significant anticoccidial effects in vivo.

Zinc Oxide Nanoparticles Blunt Potassium-Bromate-Induced Renal Toxicity by Reinforcing the Redox System.

Potassium bromate (PB) is a general food additive, a significant by-product during water disinfection, and a carcinogen (Class II B). The compound emits toxicity depending on the extent of its exposure and dose through consumable items. The current study targeted disclosing the ameliorative efficacy of zinc oxide nanoparticles (ZnO NPs) prepared by green technology in PB-exposed Swiss albino rats. The rats were separated into six treatment groups: control without any treatment (Group I), PB alone (Group II), ZnO alone (Group III), ZnO NP alone (Group IV), PB + ZnO (Group V), and PB + ZnO NPs (Group VI). The blood and kidney samples were retrieved from the animals after following the treatment plan and kept at -20 °C until further analysis. Contrary to the control (Group I), PB-treated rats (Group II) exhibited a prominent trend in alteration in the established kidney function markers and disturbed redox status. Further, the analysis of the tissue and nuclear DNA also reinforced the biochemical results of the same treatment group. Hitherto, Groups III and IV also showed moderate toxic insults. However, Group VI showed a significant improvement from the PB-induced toxic insults compared to Group II. Hence, the present study revealed the significant therapeutic potential of the NPs against PB-induced nephrotoxicity in vivo, pleading for their usage in medicines having nephrotoxicity as a side effect or in enhancing the safety of the industrial use of PB.

Disulfiram Enhances the Antineoplastic Activity and Sensitivity of Murine Hepatocellular Carcinoma to 5-FU via Redox Management.

The efficacy of anticancer drug 5-FU is suppressed due to various factors, including severe side effects and decreased insensitivity during prolonged chemotherapy. Elevated endogenous copper (Cu) levels are one of the prominent hallmark features of cancer cells. In the present investigation, this feature was targeted in diethyl nitrosamine-phenobarbital-induced hepatocellular carcinoma (HCC) in a rat model system by an established anticancer drug, 5-FU, co-administered with copper and its chelating agent, disulfiram. After treatment with the test chemicals in HCC-induced rats, blood and liver samples were subjected to biochemical, molecular, and histopathological analyses. The analysis revealed that reactive oxygen species-mediated oxidative stress is the crucial etiological reason for the pathogenesis of HCC in rats, as evidenced by the significantly compromised activity of major antioxidant enzymes and elevated levels of oxidative damaged products with major histological alterations compared to the control. However, the combination of 5-FU with DSF demonstrated a significant improvement in most of the parameters, followed by 5-FU-Cu in the combination-treated groups. The combination treatment improved the histological details and triggered apoptosis in the cancer cells to a remarkable extent, as the levels of cleaved PARP and caspase-3 were significantly higher than those in the HCC rats treated with the drug alone. The present study envisages that manipulating the Cu-level greatly enhances the antineoplastic activity of 5-FU and sensitizes cancer cells to the increased efficacy of the drug.

Novel 3-phenyl-1- (alkylphenyl)-9-oxa-4-azaphenanthren-10-ones as inhibitors of some enzymes: synthesis, characterization, biological evaluation and molecular docking studies.

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, 1H NMR, 13C spectroscopy and elemental analysis. The synthesized Compounds 5a-f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d, 3f, 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively.Communicated by Ramaswamy H. Sarma.

Morphological and Molecular Characterization of Myxobolus nkondjockei sp. nov. (Myxozoa: Myxobolidae), A Parasite of Labeo batesii Boulenger, 1911 (Teleostei: Cyprinidae) from Makombè River in Cameroon.

PURPOSE: Myxozoans are economically important group of metazoan parasites, which can cause diseases in a large variety of commercially important fishes. Increased knowledge on molecular features has shown that traditional descriptive characters may be misleading. Combination of both descriptive and molecular features is therefore necessary for an integrated taxonomic assessment. METHODS: Cyprinid Labeo batesii, sampled in the Makombè River at Nkondjock in Cameroon were examined for myxosporeans. Identification of parasite species was based on morphological and molecular sequence analyses of myxospores. Phylogenetic analysis was performed using maximum likelihood (ML) and Bayesian inference (BI) methods. RESULTS: The scales of L. batesii were infected by Myxobolus nkondjockei sp. nov Their mature myxospores are ovoid in frontal view and lenticular in lateral view, with two rounded ends. These myxospores measured 10.3 (10-10.9) µm length and 8.0 (7.3-8.5) µm width. Myxospores have two ovoid and equal sizes polar capsules. They measured 4.5 (4.0-5.0) µm in length and 2.4 (2-2.9) µm in width. Polar tubules were coiled in 4-5 turns perpendicular to the longitudinal axis of the polar capsules. Phylogenetic analysis of the 18S rDNA sequence show clustering of M. nkondjockei sp. n. close to an undetermined species Myxobolus sp. reported infecting gill lamellas of Labeo rohita from India. CONCLUSION: The morphological, molecular and phylogenetic data provided for M. nkondjockei sp. n. are solid basis for further identification of this myxozoan of which pathogenicity probably plays an economic role at culturing the hosts.

Ameliorative effect of L-carnitine on lambda-cyhalothrin-induced anatomical and reproductive aberrations in albino mice.

The objective of this research was to look at how the pesticide lambda-cyhalothrin (LCT) affected the liver, kidney, testis, and ovary of albino mice; and on morphological and skeletal features of the newborn of treated females. The study also aimed to test the ameliorative effects of L-carnitine (LC) against (LCT). Five sets of mice were created, Group 1 acted as the control, while Group 2 received a high dose of LCT, Group 3 received a high dose of LCT + LC, Group 4 received a low dose of LCT that was a residue of in khat (Qat), and Group 5 received a low dose of LCT + LC. The findings revealed that the treated groups' body weights were reduced significantly, whereas the absolute and relative weights of the liver in all groups were statistically decreased insignificantly. There were histopathological changes in the tissues in groups 2 and 4. While the tissues of the ovary and testis showed recovery in groups 3 and 5. When compared to the control group, the values of the seminiferous tubules parameters were statistically significant in the 3 and 5 groups. The newborn had a high dose of pesticides and showed some malformations in the skeleton. However, in group 3 the skeletal malformation was minimized and in-group 5 the skeleton malformations had completely disappeared. It could be concluded that LCT is highly harmful to mouse tissues and caused neonatal malformations, whereas LC has a marked protective effect against LCT.

Supplementation with selenium nanoparticles alleviates diabetic nephropathy during pregnancy in the diabetic female rats.

The bioactivity of nanoparticles has engendered a promise in scientific communities for developing novel therapeutic strategies. This study investigated the protective effects of selenium nanoparticles (SeNPs) against kidney injury in streptozocin-induced diabetes during pregnant (DDP) rats. The female rats were separated into three groups (n = 8). Group 1 received the vehicle, normal saline. Group 2 received a single intraperitoneal dose of 50 mg/kg of streptozocin. Group 3 received a single intraperitoneal injection of 50 mg/kg of streptozocin, followed by treatment with SeNPs at a dose of 2.5 mg/kg twice a week for 6 weeks (1 week before gestation and continuing for 5 additional weeks). The structure formed by the fabricated SeNPs with citric acid in the presence of ascorbic acid indicated that nano-Se was associated with a carbon matrix. The diabetic group suffered from polyuria, a reduction in body weight, delayed gestation, and only 40% successful pregnancy compared with the control rats. Interestingly, SeNPs significantly reduced the rate of urination, accelerated the start of gestation, and increased the percentage of successful pregnancy in females with DM. Severe changes were observed in the pancreatic ß-cells of the diabetic rats, with darkly stained and fragmented chromatin in nuclei, while SeNPs partially restored the normal morphological features of the pancreatic ß-cells. The concentrations of urea, creatinine, MDA, and glucose were significantly increased in the diabetic rats, while GSH was significantly reduced compared with controls. Interestingly, SeNPs restored all of these parameters to values at or near control levels. SeNPs were capable of improving the histological structure of the kidney in mothers with DDP. Hence, the present work is relevant to GDM demonstrating SeNPs shielding the kidney structure and function in vivo.

Morphological Redescription and Phylogenetical Position of Ceratomyxa truncata Thelohan (1895) and Coccomyxa morovi Léger and Hesse, 1907 (Myxozoa: Myxosporea) Infecting the Gall Bladder of Sardina pilchardus (Walbaum) from Tunisian Coast.

PURPOSE: Two myxosporean species have been, so far, independently reported from the gallbladder of the European pilchard, Sardina pilchardus (Walbaum) (synonym Clupea pilchardus) in the Northern shore of the Mediterranean Sea; Ceratomyxa truncata Thélohan, and Coccomyxa morovi Léger and Hesse, 1907. The two species were described with incomplete morphological data and based only on line drawings of their mature myxospores. METHODS: During a parasitological survey in the Southern shores of the Mediterranean coast in the gulf of Gabès off Tunisia, two coelozoic myxosporean species were found in the European pilchard and described using morphological and molecular phylogenetic tools. Morphological characterization was based on the mature myxospore study and some vegetative stages. The SSU rDNA sequences were performed for molecular and phylogenetic study. RESULTS: The most frequently encountered species belongs to the genus Ceratomyxa Thelohan, 1892. The second species belongs to the genus Coccomyxa. Morphological examinations, allowed us to match these two recorded species with Ceratomyxa truncata and Coccomyxa morovi, respectively, as previously described in the same host species referring to the original manuscripts instead of some morphological differences. Molecular analyses based on the partial SSU rDNA sequences did not much with any of the previously reported myxozoan sequences. Phylogenetic analysis positioned C. truncate in a well-supported clade including Ceratomyxa ssp. from Mediterranean Sea, while C. morovi was positioned on the basis of the subclade grouping all Coccomyxidae species. CONCLUSION: We provided herein a first morphological redescription of Ceratomyxa truncata and Coccomyxa morovi parasite of Sardina pilchardus from the Southern shores of the Mediterranean Sea and we successfully obtained the SSU rDNA sequences of these two species and positioned them in the phylogenetic tree.

Melatonin Alleviated Potassium Dichromate-Induced Oxidative Stress and Reprotoxicity in Male Rats.

Melatonin (ML) is a potent antioxidant that reduces oxidative stress. This study was designed to examine the protective effect of melatonin on potassium dichromate- (PDC-) induced male reproductive toxicity. Forty rats were divided into five groups: the control group, rats administered PDC orally (10 mg/kg body weight) for eight weeks, rats administered ML intraperitoneally at doses of either 2.5 or 5 mg/kg followed by the administration of PDC, and rats administered 5 mg/kg ML only. The treatment of rats with PDC led to a decrease in the levels of plasma sex hormones, glutathione, superoxide dismutase, catalase, carnitine, sperm count, and motility. Testicular malondialdehyde levels, nitric oxide concentrations, and abnormalities increased significantly in the PDC group. Melatonin administration to the PDC-treated rats reduced the increase of malondialdehyde and restored the activity of antioxidant enzymes (superoxide dismutase and catalase), glutathione, and sex hormone levels. Moreover, ML attenuated PDC-induced increase in levels of tumor necrosis factor-alpha or interleukin-6. ML alleviated histopathological changes and an increase of p53-positive immune reaction due to PDC. Furthermore, ML inhibited PDC-induced decrease in the DNA content of spermatogenic cells. This study proposed that melatonin may be useful in mitigating oxidative stress-induced testicular damage due to potassium dichromate toxicity.

Samsum ant venom protects against carbon tetrachloride-induced acute spleen toxicity in vivo.

Many active molecules used in the development of new drugs are produced by ants. Present study assessed antioxidant and anti-inflammatory properties of Samsum ant venom (SAV) extract in carbon tetrachloride (CCL4)-induced spleen toxicity. Toxicity and oxidative stress were measured in four experimental groups: a negative control group without any treatment, a positive control group (CCl4-treated rats; a single dose of 1 ml/kg CCL4), an experimental group of CCl4-treated rats co-treated daily with SAV (100 µl), and a group to determine safe use with rats treated only with SAV (100 µl) daily for 3 weeks. CCl4-treatment led to an elevation in toxicity and oxidative stress. CCl4 significantly elevated malondialdehyde (MDA) levels, as well as expression of inhibitor of κB (IκB) and tumor necrosis factor-α (TNF-α) proteins. On the other hand, a decrease in glutathione (GSH) and catalase (CAT) levels were detected in CCl4-treated rats. Co-treatment with SAV was found to reduce these inflammatory and oxidative parameters. SAV elucidated a significant recovery of MDA concentration as well as a significant restoration in GSH levels compared to CCl4-treated rats; however, SAV increased CAT levels compared to normal rats. Hence, SAV was found to restore splenomegaly induced in CCl4-treated rats. Histopathological analysis also favored the biochemical analysis showing improvement in splenic architecture in CCl4 and SAV co-treated rats. The antioxidant properties of SAV may potentially enhance anti-inflammatory actions and improve spleen structure and function in CCl4-challenged rats.

Curcumin-containing Silver Nanoparticles Prevent Carbon Tetrachloride- induced Hepatotoxicity in Mice.

BACKGROUND: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. METHODS: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. RESULTS: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that the CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPscurcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. CONCLUSION: Administration of AgNPs-curcumin resulted in significant anti-oxidant activity in vivo. This agent has the potential to prevent hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

Determining the time needed for workers to acclimatize to hypoxia.

This study aimed to determine the influence of intermittent hypoxia and the days required for a worker to be acclimatized in high-altitude countries. We conducted an experimental study. Ten nonsmoking male students were randomly recruited from King Saud University. Fourteen days of exposure to intermittent normobaric hypoxia (15%) was the independent variable. Heart rate (HR), respiratory frequency (RF), minute ventilation (VE), respiratory exchange ratio (RER), tidal volume (VT), oxygen uptake (VO2),VO2/kg, VO2/HR, VE/VO2, and VE/VCO2 were the dependent variables. Our results showed that 12 days of exposure to intermittent hypoxia were sufficient for workers to acclimatize to hypoxia based on their respiratory responses (i.e., HR, RF, VE). This type of acclimatization session is very important for workers who are suddenly required to work in such an environment, because prolonged exposure to high altitude without acclimatization leads to cell death due to a lack of oxygen, and this, in turn, puts workers' lives at risk.

The Alleviative Effect of Vitamin B2 on Potassium Bromate-Induced Hepatotoxicity in Male Rats.

Potassium bromate (PB) is a food enhancer, water disinfection by-product, and a proven carcinogen. It elicits toxicities in the living organism due to exposure and in a dose-dependent manner. The present study discourses the ameliorative efficacy of riboflavin (RF) in PB-administered rodents. The animals were distributed into five treatment groups: control (group I), PB alone (group II, 150 mg/kg), RF alone (group III, 2 mg/kg), PB+RF1 (group IV, 150 mg/kg + 2 mg/kg), and PB+RF2 (group V, 150 mg/kg + 4 mg/kg). After the round of the treatment, the animals were sacrificed to collect their blood and liver samples for the detailed analysis. Group II depicted perturbed liver functions evidenced by altered serum and toxicity markers along with the disturbed redox balance. Also, these biochemical results were found harmonious with histopathological analysis and comet assay. However, group III showed no noticeable alteration in the same parameters, whereas the combination groups (IV and V) exhibited dose-dependent amelioration in the PB-induced toxicities. Interestingly, RF favored apoptosis concomitant with suppressing the necrosis in the PB-challenged groups, as shown by the activity of caspase-3 and lactate dehydrogenase. Histopathological analysis and comet assay further consolidate these results. Hence, RF has significant alleviative property against PB-induced hepatotoxicity in vivo that can be used in the consumer items containing the toxicant.

Diabetes-Mediated Toxicity Resulted in the Expression of CD80 and CD86 on Neutrophils after Delayed Wound Healing in Male Rats.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) play an essential role in the innate immune response, and their number increases after prolonged inflammatory diabetic wounds and prolonged wounds in older rats. The expression of CD80 and CD86 on PMNs confirms their participation in acquired immunity, wherein these molecules are involved in antigen presentation. MATERIALS AND METHODS: We investigated CD80 and CD86 expression on PMNs by flow cytometry and analyzed the mRNA expression of neutrophil chemoattractants macrophage inflammatory protein-2 (MIP-2) and MIP-1α by real-time polymerase chain reaction (PCR) in diabetic wound, which was healed by a camel milk peptide (CMP). The animals were allocated to the following wounded groups: control, diabetic (DM), and diabetic treated with CMP (DM-CMP). RESULTS: Alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase levels were elevated in DM rats but decreased in peptide-treated rats. The expression of CD80 and CD86 was significantly higher in DM rats with prolonged wounds than in control rats. The expression of both markers was restored to normal levels in diabetic rats treated with CMP. RT-PCR analysis revealed the upregulation in MIP-2 mRNA expression in DM rats. However, neutrophil number at wounded sites of DM rats declined at day 1 after wounding as compared to that in control rats. MIP-2 mRNA expression and neutrophil number were restored in CMP-treated diabetic rats. CONCLUSION: Prolonged wound stress induced toxicity in DM rats and significantly increased the expression of CD80 and CD86 on PMNs. CMP peptide ameliorated the levels of toxicity markers, CD80 and CD86, and chemoattractant molecules in diabetic rats.

Chemopreventive effect of riboflavin on the potassium bromate-induced renal toxicity in vivo.

Potassium bromate (PB) is a general food additive, flavor enhancer, a by-product of water disinfection, and a class 2 carcinogen. It exerts various toxic effects in a dose- and time-dependent manner in vivo. This study is to explore the chemopreventive efficacy of vitamin B2 (riboflavin, RF) in PB-administered Swiss albino rats. The rats were distributed into five groups: control (group 1), PB alone (group 2, 150 mg/kg), RF alone (group 3, 2 mg/kg), PB + RF1 (group 4, 150 and 2 mg/kg), and PB + RF2 (group 5, 150 and 4 mg/kg). All the rodents were sacrificed after the completion of the treatment cycle. Then, blood and kidney samples were subjected to biochemical analysis. Group 2 demonstrated vivid signs of renal toxicities evidenced by altered renal function markers (urea, creatinine, albumin, glutathione-S-transferase) and redox status parameters (superoxide dismutase, catalase, glutathione reductase, reduced glutathione, lipid, and protein oxidation products). However, group 3 exhibited a slight alteration in many of the parameters while groups 4 and 5 demonstrated dose-dependent chemopreventive efficiency of RF against PB-induced alterations. Besides, RF seemed to facilitate apoptosis as well as inhibition of the necrosis in the PB-pre-challenged groups, as demonstrated by the cleaved PARP and lactate dehydrogenase activity. Also, the histopathological analysis and comet assay validate the biochemical results of the treatment groups significantly. All these results plead that RF has a significant chemopreventive property against PB-induced toxicity in vivo. Therefore, RF is a suitable agent in preventing the PB-induced toxicities at the clinical and industrial levels.