Background: Colorectal cancer is among the most lethal malignancies worldwide and represents the second most commonly diagnosed cancer in both males and females globally. According to the Saudi Health Council (2020), colorectal cancer ranks first among Saudi males and third among Saudi females. The present study aimed to investigate the therapeutic potential of Adansonia digitata nanoparticles against colorectal cancer induced by SW620 human colorectal cancer cells in mice. Results: The findings indicate that Adansonia digitata nanoparticles may represent a potential adjunctive therapeutic strategy for the treatment of colorectal cancer. Conclusions: Adansonia digitata nanoparticles (ADNPs), particularly the encapsulated formulation (ADNPs2), demonstrated promising therapeutic potential in colorectal cancer. Treatment with ADNPs improved colonic histoarchitecture and modulated key inflammatory and apoptotic signaling pathways. Although several molecular markers did not exhibit statistically significant changes, consistent pro-apoptotic trends, downregulation of transforming growth factor-β (TGF-β), and reduced tumor invasion were observed, indicating notable anticancer activity. These findings suggest that ADNPs2 may represent a potential adjunctive strategy for the management of colorectal cancer.
Background: Berberine represents a promising supplement with several health benefits. Thus, this study aimed to investigate the efficacy of berberine in reducing mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female mice.Materials and Methods: A total of 40 virgin female mice were segregated into four groups: an untreated control group, a group treated with a daily oral dose of berberine (BBR) extract (25 mg/kg), a group injected with a single dose of 50 mg/kg DMBA in the breast fat pad, and a group treated with DMBA, similar to the third group. After 1 week of injections, the animals were treated with BBR extract, as in the second group.Results: Animals treated with DMBA for mammary carcinoma induction showed increases in liver enzymes (ALT, AST, and ALP), kidney biomarkers (BUN, UA, and CRT), and an oxidative stress marker (MDA). Meanwhile, DMBA also promoted a decrease in the antioxidant marker (GSH) and a minor elevation in estrogen levels. Conversely, the progesterone levels increased significantly, along with those of proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)). The histopathological analysis revealed carcinoma cells in the breast tissue, with a marked desmoplastic response. Meanwhile, the uterus showed hyperplasia and dysplasia of endometrial epithelia. The immunohistochemical analysis for Ki-67 expression revealed an intense immunoreaction associated with carcinoma proliferation in the breast. In contrast, the treatment with BBR extraction one week after the induction of mammary carcinoma by DMBA resulted in a significant decrease in liver enzymes and kidney biomarkers, as well as a reduced MDA level and a higher GSH level due to oxidative stress reduction, along with a variance in female hormone levels and a decrease in cytokines. Furthermore, the histopathological analysis showed a decline in the occurrence of carcinoma and desmoplastic response in the breast, as well as less hyperplasia and dysplasia of endometrial epithelia, and a lower incidence of Ki-67 expression in the breast.Conclusion: This study observed that berberine extract possessed a potent effect in reducing the mammary carcinoma induced by DMBA in female mice.
This study investigated the potential lung-related side effects of abemaciclib in virgin female mice. Animals were divided into four groups: Group 1 (control) received clean drinking water; Group 2 received abemaciclib orally (50 mg/kg/day) for 28 days; Group 3 was given a single dose of 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg) to induce mammary carcinoma; and Group 4 received DMBA followed by abemaciclib treatment (50 mg/kg/day for 28 days) starting 10 days post-induction. Biochemical, histopathological, and immunohistochemical analyses were performed, including hormonal assays, liver enzymes, kidney biomarkers, oxidative stress markers (malondialdehyde [MDA] and catalase [CAT]), and adiponectin/TNF-α expression. DMBA administration significantly elevated estrogen, progesterone, liver enzymes, kidney biomarkers, and MDA, while reducing CAT activity. Abemaciclib treatment decreased estrogen and progesterone levels but further increased liver enzymes, kidney biomarkers, MDA, and reduced CAT. Breast histopathology in the DMBA group revealed invasive ductal adenocarcinoma with strong desmoplastic reaction, whereas abemaciclib treatment reduced tumor size and stromal reaction. Lung tissue of the DMBA group showed severe inflammation, epithelial hyperplasia, and dysplasia. Abemaciclib-treated lungs exhibited interstitial inflammation, fibrosis, and vascular thrombosis, indicating aggravated pulmonary changes. Immunohistochemically, DMBA reduced adiponectin expression in the breast, which was restored by abemaciclib. Conversely, TNF-α expression in the lung was increased by DMBA and further elevated after abemaciclib. In summary, DMBA successfully induced mammary carcinoma and lung toxicity. While abemaciclib reduced breast tumor burden, it was associated with exacerbated pulmonary toxicity, suggesting the need for careful evaluation of its lung-related side effects.
Introduction: The present study aimed to investigate the capability of Asparagus officinalis (AOE) to ameliorate hepatosplenic toxicity induced by food additive monosodium glutamate (MSG). Materials and Methods: Forty healthy Albino male mice were segregated into four groups; first group took clean water and played as control, second group was treated orally and daily with 500 mg/kg of AOE for 4 weeks, third group received orally and daily 30 mg/kg of MSG for 4 weeks, and fourth group received AOE 1 h before receiving MSG as described previously for 4 weeks. Results: MSG treatment caused a significant increase in white blood cell count, decrease in red blood cell count and HB. Biochemical analysis revealed disturbance of liver enzymes, lipid profile, and kidney biomarkers, besides significant raising of oxidative stress (malondialdehyde) and lowering of antioxidant enzymes (glutathione). Histopathological examination showed marked alterations in the liver as degeneration of hepatocytes and accumulation of infiltrative cells besides hyaline degeneration in spleen. Immunohistochemical analysis exhibited a high incidence of Nr-f2 and tumor necrosis factor (TNF)-α expressions referring to intense oxidative stress and inflammation. Moreover, treatment with AOE before MSG administration with 1 h resulted in modulation of all disturbed previous biochemical domains. Histopathological analysis showed a marked reduction of liver and spleen alterations; also, immunohistochemical analysis displayed less expression of Nr-f2 and TNF-α, indicating a reduction of oxidative stress and inflammation. Conclusion: The present work concluded that AOE could reduce the hepatosplenic toxicity induced by MSG attributed to its rich content of bioactive components such as saponins, flavonoids, and Vitamin C.
Type 1 diabetes encompasses a spectrum of metabolic disorders marked by insulin deficiency, resulting in elevated blood glucose levels, commonly referred to as hyperglycemia. This persistent condition often precipitates lipid profile abnormalities, causing cholesterol alterations, low-and high-density lipoproteins, and triglycerides. The liver is particularly vulnerable to increased oxidative stress and inflammatory responses, which activate the transcription of pro-apoptotic genes and ultimately contribute to hepatocyte damage. This study analyzed the potential therapeutic role of raspberry ketone (RK), a natural antioxidant with antiapoptotic and anti-inflammatory properties, in male albino rats with induced type 2 diabetes. Fifty rats were equally divided into five groups: control, rats orally administered 200 mg /kg Body Weight (BW) RK for 5 days, diabetic rats intramuscularly injected once with 60 mg/kg BW streptozotocin, streptozotocin-induced diabetic rats orally administered 200 mg/kg BW RK for 5 days, and streptozotocin-induced diabetic rats orally administered 100 mg/kg metformin. Streptozotocin treatment significantly affected blood biochemical parameters, lipid profiles, oxidative stress markers, immunotoxicity biomarkers, and DNA damage biomarkers. Conversely, RK efficiently ameliorated the toxic effects of streptozotocin on the liver by reducing the pathological and biochemical changes associated with diabetes through its antioxidant and anti-inflammatory properties. Therefore, incorporating RK into the diet of diabetic patients can help prevent hepatocyte damage associated with diabetes. In conclusion, oral administration of RK exerts hepatoprotective effects by offering antioxidant, antiapoptotic, and anti-inflammatory properties against streptozotocin-induced type 1 diabetes in male rats.
S EMAGLUTIDE (S) is a GLP-1 receptor agonist; Tirzepatide (T) has dual GLP-1/GIP receptor agonism. This research compared their therapeutic effects and adverse reactions in a type 2 diabetes mellitus (T2DM) mouse model. Body weight, blood glucose, lipid profile, insulin, and IGF1 were estimated, as well as histopathological examination and gene expression. S and T independently led to prominent body weight reduction in diabetic mice, as well as enhancements of glucose and lipid profiles. However, histological examination showed that pancreas hemorrhage and intestine ulceration appeared after treatment. Immunohistochemistry and RT-PCR analysis revealed that insulin and glucagon expression were partially restored, CYP2E1 was over-expressed at a lower level after therapy. In conclusion, Semaglutide and Tirzepatide showed similar metabolic advantages; however, they caused significant changes in intestine and pancreatic structure, emphasizing the necessity for careful assessment over the long term.
Myocardial infarction (MI) is a pathological condition associated with various cardiovascular diseases and leads to heart failure. Nuclear factor-kappa B (NF-κB) is upregulated in the infarcted heart. G protein-coupled receptor kinase 5 (GRK5) also plays a complex role in both tissue repair and maladaptive hypertrophy in cardiovascular diseases; however, its effect on NF-κB-mediated inflammation has not yet been elucidated. Thus, this study aims to investigate the effects of Amlexanox (AMX), a potential GRK5 inhibitor, in an animal model of MI by assessing its impact on GRK5-mediated NF-κB/inflammatory processes. Thirty-two male mice were randomly allocated into four groups: control, MI, (MI treated with vehicle (MI + V), and MI + AMX (AMX: 2.5 mg/100 g/day). MI was induced using ISO on days 21 and 22. The cardioprotective impacts of Amlexanox were verified by evaluating cardiac injury, inflammatory biomarker concentrations, and histopathological alterations in cardiomyocytes. MI induction was confirmed by increases in heart weight/body weight ratio (HW/BW) (p < 0.001), troponin (p < 0.001), creatine kinase (p < 0.001), and LDH (p < 0.001). Treatment with AMX resulted in a significant reduction in cardiac injury biomarkers (p < 0.001) and IL-6 (p < 0.05). The protein level of NF-κB(p65) and NF-κB(p105) was significantly increased in cardiac myocytes of the MI group. Treatment with AMX led to a significant decrease in NF-κB(p65) and (p105) expression (p < 0.01 and p < 0.001, respectively), and GRK5 and MEF2α protein levels were also upregulated. In conclusion, AMX shows potential cardioprotective effects by modulating the GRK5/MEF2-mediated NF-κB inflammatory signaling pathway.
Purpose: To determine the effect of PD173074 on mammary carcinoma. Methods: Virgin female mice were randomly divided into 4 groups of 10 mice per group. Group 1(control) received clean water, group 2 received an oral dose of 50 mg/kg PD173074 twice a week, group 3 received a single dose of 50 mg/kg 7,12-Dimethylbenz(a)anthracene (DMBA) in the breast for carcinoma induction, group 4 received DMBA and after that treated with PD173074 one week later for 4 weeks. Hormonal analysis, oxidative stress, levels of cytokines IL6 and TNF-α, and histopathological and immunohistochemical analysis were carried out. Results: Treatment with PD173074 significantly lowered estrogen, progesterone, oxidative stress indices, cytokines IL6, and TNF-α levels (p < 0.05) raised due to carcinoma induction. Pyrido (2,3-d) pyrimidine derivative PD173074 lowered the Nottingham histopathological score and reduced the incidence of invasive ductal carcinoma. Furthermore, immunohistochemical analysis showed that posttreatment with PD173074 significantly decreased K167 expression (p < 0.05). Conclusion: PD173074 significantly reduces estrogen, progesterone, oxidative stress indices, cytokines, TNF-α, Nottingham histopathological score, and KI-67 expression. Additional studies would be required to validate the actual mechanisms of this drug action.
Background Breast cancer remains a significant global health burden despite advancements in treatment. While conventional therapies often induce adverse effects, there is growing interest in exploring natural alternatives. Acacia nilotica, a traditionally used medicinal plant, has shown promise in cancer management. Purpose This study investigated the therapeutic potential of A. nilotica extract and nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in albino rats. Methods The formation of A. nilotica crude solution and nanoparticles was done and characterized via dynamic light scattering (DLS) and Fourier-transform infrared spectroscopy (FTIR). A total of 60 female Wistar albino rats were divided into six groups (10 rats/group) and received care in compliance with the state authorities following the Saudi Arabian rules of animal protection. The animals in the first group were given distilled water, while those in the second group were administered DMBA (50 mg/kg). The third and fourth groups were treated with 10 mg/kg of the A. nilotica crude solution and nanoparticles, respectively. In the fifth and sixth groups, A. nilotica crude solution and nanoparticles were administered with 10 mg/kg after DMBA-induced breast cancer in rats, respectively. After sacrificing the rats, the blood and breast tissues were collected from each rat and processed for histological and apoptotic markers analyses. Results Our findings indicated that the average size of nanoparticles was 162.5 nm in diameter with 0.145 as a polydispersity index (PDI). Functional groups were confirmed via FTIR analysis for A. nilotica crude solution and nanoparticles. Histopathological analysis revealed a marked reduction in tumor size and cellular proliferation in nanoparticle-treated groups. Our data demonstrated that both formulations significantly inhibited tumor growth and induced apoptosis, as evidenced by altered Bcl-2 and BAX expression. Conclusion These findings suggest that A. nilotica nanoparticles warrant further investigation as a potential therapeutic strategy for breast cancer.
Drug addiction is considered a worldwide concern and one of the most prevailing causes of death globally. Opioids are highly addictive drugs, and one of the most common opioids that is frequently used clinically is fentanyl. The potential harmful effects of chronic exposure to opioids on the heart are still to be elucidated. Although β-lactam antibiotics are well recognized for their ability to fight bacteria, its protective effect in the brain and liver has been reported. In this study, we hypothesize that β-lactam antibiotic, ceftriaxone, and the novel synthetic non-antibiotic β-lactam, MC-100093, are cardioprotective against fentanyl induced-cardiac injury by upregulating xCT expression. Mice were exposed to repeated low dose (0.05 mg/kg, i.p.) of fentanyl for one week and then challenged on day 9 with higher dose of fentanyl (1 mg/kg, i.p.). This study investigated cardiac histopathology and target genes and proteins in serum and cardiac tissues in mice exposed to fentanyl overdose and β-lactams. We revealed that fentanyl treatment induced cardiac damage as evidenced by elevated cardiac enzymes (troponin I). Furthermore, fentanyl treatment caused large aggregations of inflammatory cells and elevation in the areas and volumes of myocardial fibers, indicating hypertrophy and severe cardiac damage. Ceftriaxone and MC-100093 treatment, However, induced cardioprotective effects as evidenced by marked reduction in cardiac enzymes (troponin I) and changes in histopathology. Furthermore, ceftriaxone and MC-100093 treatment decreased the levels of hypertrophic genes (α-MHC & β-MHC), apoptotic (caspase-3), and inflammatory markers (IL-6 & NF-κB). This study reports for the first time the cardioprotective effect of β-lactams against fentanyl-induced cardiac injury. Further studies are greatly encouraged to completely identify the cardioprotective properties of ceftriaxone and MC-100093.
Bisphenol A(BPA) is a non-persistent, anthropic compound and continues to be ubiquitous in the environment. Since BPA is estrogenic in nature, its exposure induces adverse cellular responses associated with oxidative stress and inflammation. Hesperetin, a major flavonoid present in lemons and sweet oranges exhibits a broad spectrum of pharmacological effects attributed to its potent anti-inflammatory and antioxidant status. The current study reports the 'green' synthesis of nano hesperetin (NHsp) followed by characterization that included; Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). In accordance with the findings, the mean size of the synthesized nanoparticles was 139.9 nm with a PDI of 0.362. The morphotype was primarily spherical and rod shaped. This was followed by a comparative assessment of the ameliorative efficacy of bulk and nano hesperetin against BPA-induced hepatotoxicity in rat. The findings showed that post-exposure to 250 mg/ kg of BPA for 21 days significantly enhanced the pro-inflammatory cytokines (IL-6, IL-8, IL-1 beta, TNF-alpha), in the serum with a concomitant upregulation in the mRNA expression of Nrf 2(Nuclear factor erythroid 2-related factor) factor in the liver. Treatment with both bulk hesperetin (Hst) and nano hesperetin (NHst) reduced the levels of cytokines and expression of hepatic Nrf2 factor. This was paralleled by the modulatory effects on the histology of liver and kidney which were reversed on treatment. Taken together, the nano hesperetin was more efficacious in alleviating the BPA-induced toxicity. Thus,hesperetin and its nano formulation could be potentially promising nutraceuticals in medicine and industry.
Purpose: To determine the inhibitory effect of Asparagus officinalis extract (AOE) on allergic asthma induced by carrageenan (CGN). Methods: Forty male mice were divided into 4 groups: the 1st group was untreated control; 2nd group was treated orally and daily with 500 mg/kg AOE for one week; the 3rd group was treated with single dose of CGN 2 %w/v (200 mu L/mice) intraperitoneally and left for one week; while the 4th group was treated first with CGN as in 3rd group and treated with AOE as 2nd group after CGN injection for one week. After treatment, the animals were sacrificed and blood samples were subjected to white blood cell count. IL6 and TNF-alpha were measured in the lung homogenate while histopathological analysis was performed for lung samples. Results: A single dose of CGN resulted in significant increase in white blood cell (WBC) count and proinflammatory cytokines (IL6 and TNF-alpha; p < 0.05). Histopathological analysis showed severe lung alterations such as accumulation of infiltration cells that blocked alveolar sacs, over -secretion of collagenous fibers, extracellular matrix and hyaline membranes. Moreover, treatment with AOE after CGN injection significantly reduced WBC count (p = 0) and pro -inflammatory cytokines (IL -6 and TNF-alpha) that were raised by CGN (p = 0). Furthermore, AOE reduced the pathological signs that were induced by CGN leading to improvement of lung function and reduction of collagenous fibers and hyaline membranes. Conclusion: Asparagus officinalis extract reduces the allergic effect and lung pathological signs induced by CGN. Since AOE inhibits the production of inflammatory cytokines, it has the potential to be developed as a source of active pharmaceutical ingredients for the management of lung and airway injury.
One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 μg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM.
Grouper fish are among the most important components of the fisheries of many countries because they are found in warm water throughout the world. There are 15 genera and 159 species known worldwide; 8 genera and 66 species are exclusively found in the western Indian Ocean, Red Sea, and Arabian Gulf. The Summan grouper, Epinephelus summana, constitutes a considerable portion of these fisheries; therefore, this study aimed to evaluate the reproductive strategy of this important fish species. The fish samples were collected monthly for one year (from November 2020 to October 2021), and 217 fish were collected from the Red Sea of Jeddah, Saudi Arabia. The sex ratio, sexual maturation process, and spawning season were analyzed. Across all samples, landing consisted of 36.2 ± 4.7% males, 64.0 ± 5.0% females, and 3.4 ± 1.8% transitional-stage fish, with an overall significantly different male-to-female sex ratio of 1:3.3. Furthermore, males were larger than females. The maturation index (MI), gonadosomatic index (GSI), and ovarian maturation rate (OMR) values fluctuated throughout the year, indicating that E. summana has extended spawning and spawns in batches during different months of the year. However, April to May is the main spawning season, with the highest female GSI recorded. Based on the microscopic histological examination of gonads, the maturation process can be classified into five stages in both males and females. In conclusion, this fish species has a complex reproductive biology. It undergoes sexual transformation and protogynous hermaphroditism, during which individuals mature first as female and then change sex to male. The obtained data is essential for successful fishery stock conservation, management, and aquaculture development.
Background: Recent research has validated the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing glucose levels and exerting a nephroprotective role. Objective: This study aimed to examine the impact of dapagliflozin in preventing sepsis-induced acute kidney injury (AKI) and related consequences. The study used both normal and diabetic rat models to investigate whether the effectiveness of dapagliflozin is influenced by glycemia levels. Methods: Normal and diabetic Wistar albino rats were treated with dapagliflozin for two weeks and then received a single dose of lipopolysaccharide (LPS). After sepsis induction, skin and deep body temperatures were recorded every two hours. Blood and kidneys were collected for analysis using histological examination and biochemical assays. Results: Dapagliflozin attenuated the consequences of sepsis through mitigation of LPS-induced hypothermia and AKI in the normal and diabetic septic groups. Dapagliflozin regulated the serum levels of AKI markers, including creatinine and blood urea nitrogen, as well as ion levels. Dapagliflozin attenuated LPS-induced AKI through modulation of renal inflammation and oxidative stress, which showed well-abundant glomeruli. These results indicated the protective effect of dapagliflozin against LPS-induced hypothermia and AKI, which was likely unrelated to its glucose-lowering properties, as evidenced in the non-diabetic septic group. Conclusion: The outcomes suggest that dapagliflozin has a potential impact in preventing sepsis-induced hypothermia and AKI via modulation of inflammation and oxidative stress, irrespective of glycemic levels.
Nanosized lanthanum oxide particles (La2O3) are commonly utilized in various industries. The potential health risks associated with La2O3 nanoparticles, cytotoxic effects at varying doses and time intervals, and the mechanisms behind their induction of behavioral changes remain uncertain and necessitate further investigation. Therefore, this study examined in vivo hepatotoxicity, considering the quantity (60, 150, and 300 mg/kg) and time-dependent induction of reactive oxygen species (ROS) over one week or 21 days. The mice received intraperitoneal injections of three different concentrations in Milli-Q water. Throughout the experiments, no physical changes or weight loss were observed among the groups. However, after 21 days, only the highest concentration showed signs of anxiety in the activity cage ( p < 0.05). Subsequently, all animals treated with La2O3 NPs exhibited a significant loss of learning and memory recall using the Active Avoidances test, after 21 days ( p < 0.001). Markers for anti-reactive oxygen species (ROS) such as superoxide dismutase ( SOD ) were significantly upregulated in response to all concentrations of NPs after seven days compared to the control group. This was confirmed by a significant increase in glutathione peroxidase ( Gpx1 ) and pro-apoptotic Caspase-3 expression at the lowest and highest doses. Additionally, both transcription and protein levels of the anti-apoptotic BCL-2 surpassed P53 protein in a dosage-dependent manner, indicating activation of the primary anti-apoptosis pathway. After 21 days, P53 levels exceeded BCL-2 protein levels, confirming a significant loss of BCL-2 mRNA, particularly at the 300 mg/kg concentration. Furthermore, a higher transcription level of Caspase-3 , SOD , and Gpx1 was observed, with the highest values detected at the 300 mg/kg concentration, indicating the activation of cell death. Histopathological analysis of the liver illustrated apoptotic bodies resulting from La2O3 NP concentration. The investigation revealed multiple inflammatory foci, cytoplasmic degeneration, steatosis, and DNA fragmentation consistent with increased damage over time due to higher concentrations. Blood samples were also analyzed to determine liver enzymatic changes, including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and lipid profiles. The results showed significant differences among all La2O3 NP concentrations, with the most pronounced damage observed at the 300 mg/kg dose even after 21 days. Based on an animal model, this study suggests that La2O3 hepatotoxicity is likely caused by the size and shape of nanoparticles (NPs), following a dose and time-dependent mechanism that induces the production of reactive oxygen species and behavioral changes such as anxiety and memory loss.
Tivozanib is a triple vascular endothelial growth factor receptor inhibitor, recently approved for the treatment of refractory advanced renal cell carcinoma. Clinical studies showed that around 46% of patients who received tivozanib suffer from hypertension in all grades. Thus, the present study was conducted to identify the role of angiotensin-II (AngII) in the mechanism underlying tivozanib-induced vascular toxicity and hypertension. C57BL/6 male mice received tivozanib (1 mg/kg) with or without losartan (10 or 30 mg/kg) for 3 weeks. Blood pressure was recorded every 3 days, and proteinuria was measured every week. On day 21, all mice were euthanized, and samples were harvested for further analysis. Tivozanib elevated blood pressure until systolic blood pressure reached 163 ± 6.6 mmHg on day 21 of treatment with low urination and high proteinuria. AngII and its receptors, endothelin-1, and oxidative stress markers were significantly increased. While nitric oxide (NO) levels were reduced in plasma and aortic tissues. AngII type 1 receptor blockade by losartan prevented these consequences caused by tivozanib and kept blood pressure within normal range. The results showed that AngII and ET-1 might be potential targets in the clinical studies and management of hypertension induced by tivozanib.
Green synthesized silver nanoparticles (AgNPs) have been used against antibiotic-resistant bacteria and chemo-resistant cancer cells. We synthesized AgNPs from Acacia nilotica pods, evaluating their antibacterial activity against eight bacterial strains and anticancer efficiency against two colon cancer cell lines, SW620 and SW480. Expression levels of eight genes (β-catenin, APC, TP53, Beclin1, DKK3, Axin, Cyclin D1, and C-myc) were checked by a reverse transcription-polymerase chain reaction in cancer cells before and after treatment with A. nilotica extract and A. nilotica-AgNPs. Prepared nanoparticles were characterized through ultraviolet-visible (UV-vis), Zetasizer, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Fourier transform infrared spectroscopy (FTIR) was used to identify the functional group in extracts. At first, AgNPs were confirmed by a sharp peak of surface plasmon resonance at 375 nm. The Z-average size was 105.4 nm with a polydispersity index of 0.297. TEM showed particle size of 11–30 nm. The prepared AgNPs showed promising antibacterial activity against bacterial strains and cytotoxic activity against the cancer cell lines. Expression levels of all the genes were affected by extract and AgNPs treatment. Overall, this study recommended both A. nilotica pods and A. nilotica-AgNPs as attractive candidates for antibacterial and anticancer applications.