Background and Aim: This study assessed the renal toxicity of monosodium glutamate (MSG) and, for the first time, jointly examined the potential nephroprotective effects of the olive-derived compounds hydroxytyrosol (HT) and oleuropein (OLE) in an aged rat model. By doing so, it sought to address a notable gap in the existing literature by clarifying the protective roles of HT and OLE against MSG-induced renal injury. Experimental Approach: A total of 60 aged male Sprague-Dawley rats (>= 20 months old) were randomly allocated into six experimental groups. Control, MSG (600 mg/kg/day), HT (10 mg/kg/day), OLE (200 mg/kg/day), and combined treatment (MSG+HT/MSG+OLE) groups. All compounds were administered orally for 28 days. Kidney tissues were collected for biochemical and histopathological evaluation. Oxidative stress markers, antioxidant status, DNA damage, and apoptosis-related parameters were assessed, and histopathological alterations were examined using hematoxylin-eosin staining. Key Findings: Significant intergroup differences (P < 0.05) were detected for all evaluated biochemical parameters, including Total Antioxidant Capacity, Total Oxidant Capacity, Oxidative Stress Index, 8-hydroxy-2 '-deoxyguanosine, Malondialdehyde, Catalase, and Caspase-3. Histopathologically, MSG administration induced marked renal damage characterized by glomerular hypertrophy, mesangial cell proliferation, tubular epithelial degeneration, hyaline cast formation, vascular hyperemia, interstitial edema, and focal or extensive coagulative necrosis. In contrast, co-treatment with HT or OLE markedly reduced the severity and distribution of these lesions. Conclusion: The findings confirm the nephrotoxic effects of MSG and demonstrate the nephroprotective properties of both HT and OLE in a rat model, indicating potential mechanisms through which these olive-derived compounds alleviate MSG-induced renal damage.
Background and aimSmp24 and Smp43 are cationic antimicrobial peptides from the Egyptian scorpion Scorpio maurus palmatus. Prior studies showed their cytotoxic effects on various cancer cell lines, including blood, liver, lung, and breast cancers. This study explored the mechanisms of Smp24 and Smp43 in glioma (U87MG) and prostate cancer (PC3) cells.MethodsCytotoxicity was assessed after 24-h treatment (2.5-40 & micro;M) using CellTiter-Glo (R) for ATP levels and LDH assays for membrane integrity. At IC50 concentration, nuclear morphology was examined by Hoechst 33342/PI dual staining, and apoptosis by Annexin V/PI and cell cycle were analyzed by flow cytometry. Gene expression of apoptosis markers (CASP3, CASP8, CASP9, PARP1) was measured by RT-PCR. Protein activation of caspase-3 and PARP-1 was analyzed by Western blot, with caspase-3 involvement confirmed using the inhibitor Ac-DEVD-CHO.Key findings and conclusionBoth peptides reduced viability and induced cytotoxicity in a dose-dependent manner, as evidenced by decreased ATP levels and increased LDH release. Morphological apoptosis features were observed with Hoechst/PI staining and confirmed by Annexin V/PI staining. In addition, PC3 cells only showed G2/M arrest. RT-PCR indicated upregulation of apoptosis markers, and Western blot confirmed caspase-3 activation and PARP-1 cleavage. Furthermore, Ac-DEVD-CHO attenuated peptide-induced cytotoxicity, supporting caspase-dependent apoptosis. Taken together, this study shows that Smp24 and Smp43 exhibit potent cytotoxicity against glioma and prostate cancer cells through caspase-dependent apoptosis, emphasizing their potential as the novel candidates for cancer therapy.
Xylazine is a potent alpha-2 adrenergic agonist widely used in veterinary medicine and increasingly recognized as an adulterant in illicit drug markets. Accidental pediatric exposure remains rare. We report the case of a 10-year-old boy who presented four hours after being unintentionally struck by a veterinary dart containing 30 mg of 2% xylazine hydrochloride. On admission, he exhibited central nervous system depression (Glasgow Coma Scale 13), marked bradycardia (45 beats/min), and mild hyperglycemia (121 mg/dL). Intravenous atropine (0.5 mg) failed to improve the bradycardia. The patient was managed with supportive care in a pediatric intensive care unit. Heart rate and neurological status returned to baseline within 12 hours, and glucose levels normalized by 30 hours. He was discharged on the fourth hospital day without sequelae. This case highlights that low-dose parenteral xylazine exposure may produce significant toxicity in children, including atropine-resistant bradycardia.
Background and aim: Cisplatin is a successful medicinal drug and an efficient chemotherapeutic agent that has a dose-dependent hepatotoxicity. The present study aimed to examine the hepatoprotective function of cirsimaritin against cisplatin-mediated liver injury and to determine whether cirsimaritin affects the antitumor activity of cisplatin. Experimental approach: Adult male Wistar rats were pretreated with cirsimaritin (50 or 100 mg/kg, p.o.) for 7 days before a single i.p. injection of cisplatin (7.5 mg/kg). Biochemical, histological, oxidative, and molecular endpoints were evaluated. The anticancer activity of cisplatin alone or in combination with cirsimaritin was measured in MCF-7 breast cancer cells by MTT assay. Key findings: The injection of cisplatin resulted in a marked rise in serum ALT and AST levels (p < 0.001), an increase that was significantly inhibited by cirsimaritin at 50 mg/kg (p < 0.01) and 100 mg/kg (p < 0.001). The increased serum triglycerides and total cholesterol (p < 0.001) were significantly attenuated by 100 mg/kg of cirsimaritin (p < 0.05). Hepatic malondialdehyde (MDA) and NOx (nitrate/nitrite), which were elevated by cisplatin (p < 0.001), were decreased by cirsimaritin in a dose-dependent manner (p < 0.01 and p < 0.001, respectively), whereas GSH, which was downregulated by cisplatin (p < 0.001), was upregulated by cirsimaritin (p < 0.01 for 50 mg/kg; p < 0.001 for 100 mg/kg). Histopathology confirmed cirsimaritin-mediated structural restoration. In Western blot analysis, cirsimaritin downregulated nuclear factor-kappa B (NF-kappa B) (p < 0.001) and upregulated phosphorylated Akt (p-Akt) expression (p < 0.01). In MCF-7 cells, cirsimaritin (25 and 50 & micro;M) potentiated cisplatin-induced cytotoxicity did not antagonize cisplatin cytotoxicity. Conclusion: Our findings also indicate that cirsimaritin induces dose-dependent hepatoprotection against cisplatin toxicity without decreasing its anticancer activity, thus making it a good candidate as adjuvant therapy in oncology.
Background and aimSnake venom metalloproteinases (SVMPs) are abundant multidomain enzymes with diverse biological functions. This study aimed to purify and characterize a novel SVMP, CcVMP-III, from Cerastes cerastes venom and assess its protective effects in pulmonary embolism murine model.Experimental approachCcVMP-III (110 kDa) was purified by chromatographic techniques and partially sequenced using N-terminal and LC-MS/MS analyses. Biological activities were evaluated using coagulation parameters (aPTT, TT, PT), clot degradation, and fibrin plate lysis. Thromboprotective efficacy was assessed using a thrombin-induced pulmonary embolism model.Key findings CcVMP-III was identified as a class-III SVMP containing metalloproteinase, disintegrin-like, and cysteine-rich domains. It selectively prolonged aPTT and TT without affecting PT and exhibited strong fibrinolytic and thrombolytic activities. In vivo, it significantly prevented pulmonary thrombus formation, demonstrating marked thromboprotective efficacy.ConclusionThese findings emphasize the potential of CcVMP-III as a promising thromboprotective agent that may mitigate morbidity and mortality associated with thromboembolic events.
Background and aimAmong the variety of biologically active phytocompounds, polyphenols such as tannin have been found to effectively inhibit the growth of Fusarium oxysporum. Using a range of assays, the effects of gallic and tannic acid as well as seaweed crude tannin extracts (CTE) and their column chromatographic fractions 1 and 2 were investigated.Experimental approachExtraction of the tannin from seaweeds and separation using a Sephadex LH-20 column and thin-layer chromatography, then identifying the bioactive principles through GC-MS, and determination of the level of tannin using an HPLC C18 column can be accomplished. The antifungal activity was determined using diffusion bioassay, minimum inhibitory concentration (MIC), and conidial population count of F. oxysporum. The mechanism of action of the tannins was recorded by measuring the levels of F. oxysporum mycelial cellulase, amylase, protease, lipase, and xylanase.Key findingsTannic acid has greater effects than gallic acid. Turbinaria ornata CTE significantly reduced the growth of F. oxysporum. Stoechospermum marginatum tannin fraction 1 showed the highest level of antifungal activity. For crude and fractions, the MIC values are 0.6 and 0.12%, respectively. F. oxysporum growth curve lacks a stationary phase. In comparison with brown algal crude tannins, the development of F. oxysporum conidia was dramatically inhibited by gallic acid and tannic acids. When compared to other tannin fractions that were assessed, conidial production was significantly reduced by Sargassum wightii tannin F2. The results demonstrated a dose-dependent reduction of enzyme activities of F. oxysporum by seaweeds CTE. At higher concentrations, T. ornata significantly reduced amylase and pectinase activities, whereas S. wightii reduced protease, cellulase, and xylanase activities, and S. marginatum reduced lipase activity.ConclusionsTo reduce cotton wilt in the field, use column chromatographic fractions of CTE from S. wightii, S. marginatum, and T. ornata in the near future.
Experimental approachProtein cocktails were isolated from the umbrella and oral arms of A. aurita. Cytotoxicity was evaluated using MTT assays on normal colon epithelial (CCD841CON) and colorectal cancer (WiDr, HT29) cell lines. Cell migration and invasion were assessed using wound healing and 3D Matrigel-based invasion assays.Key findingsThe oral arms-derived protein cocktail selectively reduced proliferation in WiDr and HT29 cells (IC5.: 271.26 and 142.54 mu g/mL), without affecting CCD841CON cells. Migration and invasion were significantly suppressed in cancer cells, while normal epithelial cells were unaffected.ConclusionOral arms-derived venom proteins from A. aurita demonstrate selective cytotoxic and anti-invasive effects on colorectal cancer cells, indicating potential as a natural anticancer agent.
Background and AimThe groundwater quality assessment was carried out around the industrial area of the Rai block of Sonipat district, India, consecutively for three seasons during 2021 and 2022.Experimental ApproachCadmium, chromium, nickel, copper, iron, zinc, pH, temperature, TDS, EC and turbidity, were analyzed. SPSS 22 Trial version software was used for the descriptive statistics, correlation, and ANOVA.Key FindingsSeasonal trend indicated that TDS, EC and turbidity peaked during the monsoon season in both 2011 and 2022, reflecting enhanced runoff and infiltration process. pH exhibited maximum values in the pre-monsoon season of 2021 and the monsoon season of 2022, suggesting variable buffering and dilution effects. The concentrations of heavy metal ions were observed in the pre-monsoon season of 2021 and the POM season of 2022 due to seasonal differences in recharge and metal mobilization.ConclusionsHighlevels of TDS, EC, turbidity and heavy metals contamination rendered the groundwater non-potable, posing a potential risk to human health. Therefore, the application of appropriate treatment technologies like ion-exchange, adsorption and filtration is recommended to improve the groundwater quality and make it suitable for drinking purpose.
Background and aimIbotenic acid, a neurotoxin found in poisonous mushrooms, induces neurotoxic effects; however, comprehensive in vivo toxicity data remain scarce. This study aimed to systematically evaluate the toxic effects of ibotenic acid using a murine model.Experimental approachWe established a murine model and systematically evaluated its toxic effects using blood biochemical, histopathological examination, and immunohistochemistry.Key findingsIbotenic acid exhibited dose- and time-dependent toxicity. At 16 mg/kg, mice exhibited reduced activity, somnolence, and tremors, accompanied by transient changes in glucose, urea, and calcium levels that normalized within 240 min. No mortality was observed at this dose. In contrast, 33 mg/kg induced severe toxicity within 75 min, marked by significant abnormalities in ALT, UA, CK, GLU, K, and Ca levels, as well as mortality. Histopathology revealed no overt tissue damage, but showed upregulated c-fos expression at an early stage. High-dose exposure caused a significant reduction of Nissl bodies within the cerebral cortex and hippocampus. Neither neuronal density nor the number of astrocytes and microglia varied significantly across dose groups.ConclusionsThis study systematically elucidates the toxic effects of ibotenic acid, demonstrating its dose- and time-dependent impact, revealing that short-term exposure can cause behavioral abnormalities, biochemical disorders, and neuronal damage.
Background and aimHydrogen sulfide (H2S) is a common gas with an unpleasant odor similar to rotten eggs. The extent of injury from inhaled H2S depends on the gas concentration. Chronic exposure to H2S has been reported to cause immunotoxicity and inflammatory effects in the lung. However, the molecular mechanisms underlying lung injury induced by continuous, low-concentration H2S exposure remain unclear.Experimental approachTwenty male ICR mice, 6-7 weeks old, were randomly assigned to two groups. The control group was exposed to clean air (21.9% O2, 0 ppm H2S), while the H2S group was exposed to air containing H2S (21.9% O2, 5 +/- 1 ppm H2S) for 21 days.Key findings and conclusionsInhaled H2S induced pulmonary injury and fibrosis, promoted the release of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1 beta), and inhibited the anti-inflammatory cytokine IL-10. Additionally, H2S inhalation altered the expression of occludin, a tight junction-related protein. These findings enhance understanding of H2S-associated occupational health risks.
Background and aim: The Rhinella marina cane toad from Central and South America is an introduced pest that is now widely distributed throughout Australia. While the cane toad skin secretions are widely known to contain bufadienolides which are digoxin-like compounds, this research investigated other cardioactive compounds that were also present. Experimental approach: Solubilized cane toad skin secretion and HPLC separated fractions were tested in mouse isolated hearts using the Langendorff method. Key findings: Cane toad secretions caused a significant increase in developed pressure, cardiac contraction and heart rate in mouse isolated hearts when compared to digoxin alone (p < 0.05) and was inhibited by the beta-adrenoceptor antagonist propranolol (10 nM, p < 0.05). NMR analysis of HPLC seprated fractions revealed the presence of epinephrine and bufadienolides. Conclusions: The results show that multiple cardioactive agents are present in cane toad secretions with the most profound pharmacological effects caused by epinephrine.
Background and AimScorpion venoms are complex biochemical arsenals, yet research has predominantly focused on neurotoxic peptides, overlooking non-protein constituents such as lipids. This study provides the first high-resolution lipidomic characterization of the venoms of two medically significant Egyptian scorpions, Androctonus amoreuxi and Androctonus bicolor, to elucidate their species-specific lipid profiles and potential bioactivities.Experimental ApproachVenoms were milked via electrostimulation. Lipids were isolated using a methyl tert-butyl ether (MTBE) protocol and analyzed using untargeted UHPLC-MS/MS in positive and negative ionization modes. Identified lipids were functionally annotated and mapped to biological pathways using the KEGG database.Key FindingsThe venom lipidomes were remarkably diverse, with 548/527 and 479/502 distinct lipid species identified in A. amoreuxi and A. bicolor in the positive/negative modes, respectively. The dominant lipid classes included ceramides (Cer), phosphatidylcholines (PC), triglycerides (TG), and sphingomyelins (SM), with pronounced interspecies variations. A. amoreuxi venom was enriched in ceramides, while A. bicolor was characterized by higher phosphatidylethanolamine (PE) and unique phosphatidylserine (PS). KEGG analysis revealed significant enrichment in glycerophospholipid metabolism, choline metabolism in cancer, and neuroimmune signaling pathways (e.g. retrograde endocannabinoid signaling), suggesting their roles in inflammatory modulation, cell proliferation, and neuropharmacology.Conclusions and Impact StatementThis study expands current understanding of scorpion venom composition by revealing its underexplored lipidomic dimension. The identified lipids were computationally predicted to be molecular participants in apoptosis, neuroimmune modulation, and oncogenic signaling. Although functional validation and potential minor hemolymph contamination warrant further investigation, these findings provide a biochemical foundation for venom-based drug discovery, positioning lipid components as emerging scaffolds for next-generation biotherapeutics development.
