Increase In MDA Levels Research Articles

TLR2/TLR5 Signaling and Gut Microbiota Mediate Soybean-Meal-Induced Enteritis and Declined Growth and Antioxidant Capabilities in Large Yellow Croaker (Larimichthys crocea)

Soybean meal, renowned for its high yield, cost efficiency, and protein richness, serves as a pivotal plant-based alternative to fish meal. However, high soybean meal inclusion in Larimichthys crocea diets is linked to enteritis and oxidative damage, with unknown mechanisms. Our study aims to elucidate the molecular basis of soybean-meal-induced enteritis and its impact on intestinal microbiota in L. crocea. To this end, four isonitrogenous and isolipidic diets with varying soybean meal levels (0% FM, 15% SBM15, 30% SBM30, and 45% SBM45) were administered to L. crocea for 8 weeks. The results indicated that the SBM30 and SBM45 treatments significantly hindered fish growth, digestive efficiency, and protein utilization. Furthermore, high soybean meal levels (SBM30 and SBM45) activated intestinal Toll-like receptors (TLR2A, TLR2B, TLR5, and TLR22), stimulating C-Rel and mTOR protein expression and elevating ERK phosphorylation. This led to increased pro-inflammatory cytokine production (IL-1β, IL-6, and TNF-α) and decreased anti-inflammatory cytokine expression (IL-4/13A, IL-4/13B, and TGF-β), suggesting a potential signaling pathway for soybean-meal-induced enteritis. Furthermore, enteritis induced by high soybean meal levels led to oxidative damage, evident from increased MDA levels and decreased antioxidant enzyme activities (SOD and CAT). The SBM30 and SBM45 treatments increased Firmicutes and Bacteroidetes abundance in fish gut microbiota, while Proteobacteria abundance decreased. This microbiota shift may enhance soybean meal nutrient utilization, yet high soybean meal concentrations still impair growth. A soybean-meal-rich diet promotes harmful bacteria like Rhodococcus and depletes probiotics like Ralstonia, increasing disease risks. L. crocea has limited tolerance for soybean meal, necessitating advanced processing to mitigate anti-nutritional factors. Ultimately, exploring alternative protein sources beyond soybean meal for fish meal replacement is optimal for L. crocea.

Assessment of reproductive, genotoxic, and cytotoxic effects of leachate-contaminated water in male mice

Leachate-contaminated water (LCS) poses significant health risks due to its heavy metal content and altered physicochemical properties. This study examined the physicochemical parameters and heavy metal levels in LCS and assessed its reproductive toxicity, genotoxicity, and cytotoxic effects in exposed mice. Groups of mice (n = 5) were orally administered 100 μL of 30 % and 70 % LCS (v/v) twice daily for 35 days. Drinking water served as a negative control, and cyclophosphamide (Cyp) (20 mg/kg bw) as a positive control. On day 36, the mice were weighed, sacrificed, and their testicular weight, sperm count, sperm morphology, viability, acrosome integrity, and serum testosterone were examined. Oxidative stress in the testes, histopathological changes, and serum markers for liver and kidney function (SGOT, SGPT, and creatinine) were also assessed. Genotoxic effects were evaluated using a micronuclei (MN) assay. Analysis of the leachate showed altered physicochemical parameters and elevated heavy metal levels. Exposure to LCS led to a significant decrease in relative testis weight, sperm count, normal sperm morphology, viability, acrosome integrity, and serum testosterone levels. It also caused a notable increase in MDA levels and a decrease in catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) levels, along with histological changes in the testes of LCS-treated mice compared to controls. Additionally, there was a significant rise in MN formation in RBCs and elevated levels of liver enzymes and creatinine, indicating liver and renal toxicity. Histological alterations in the liver and kidneys were also observed in LCS-exposed mice. These findings suggest that LCS induces reproductive toxicity, genotoxicity, and cytotoxicity in male subjects.

Estrogen replacement therapy reverses spatial memory loss and pyramidal cell neurodegeneration in the prefrontal cortex of lead-exposed ovariectomized Wistar rats

BackgroundAlthough menopause is a component of chronological aging, it may be induced by exposure to heavy metals like lead. Interestingly, lead exposure, just like the postmenopausal state, has been associated with spatial memory loss and neurodegeneration; however, the impact of hormone replacement therapy (HRT) on menopause and lead-induced spatial memory loss and neurodegeneration is yet to be reported. AimThe present study investigated the effect and associated mechanism of HRT on ovariectomized-driven menopausal state and lead exposure-induced spatial memory loss and neurodegeneration. Materials and methodsThirty adult female Wistar rats were randomized into 6 groups (n = 5 rats/group); the sham-operated vehicle-treated, ovariectomized (OVX), OVX + HRT, lead-exposed, OVX + lead, and OVX + Lead + HRT groups. Treatment was daily via gavage and lasted for 28 days. ResultsOvariectomy and lead exposure impaired spatial memory deficit evidenced by a significant reduction in novel arm entry, time spent in the novel arm, alternation, time exploring novel and familiar objects, and discrimination index. These findings were accompanied by a marked distortion in the histology of the prefrontal cortex, and a decline in serum dopamine level and pyramidal neurons. In addition, ovariectomy and lead exposure induced metabolic disruption (as depicted by a marked rise in lactate level and lactate dehydrogenase and creatinine kinase activities), oxidative stress (evidenced by a significant increase in MDA level, and decrease in GSH level, and SOD and catalase activities), inflammation (as shown by significant upregulation of myeloperoxidase activity, and TNF-α and IL-1β), and apoptosis (evidenced by a rise in caspase 3 activity) of the prefrontal cortex. The observed biochemical and histological perturbations were attenuated by HRT. ConclusionsThis study revealed that HRT attenuated ovariectomy and lead-exposure-induced spatial memory deficit and pyramidal neurodegeneration by suppressing oxidative stress, inflammation, and apoptosis of the prefrontal cortex.

Repurposing flubendazole for glioblastoma ferroptosis by affecting xCT and TFRC proteins.

New uses of old drugs hold great promise for clinical translation. Flubendazole, an FDA-approved antiparasitic drug, has been shown to target p53 and promote apoptosis in glioblastoma (GBM) cells. However, its damaging mechanism in GBM remains elusive. Herein, we explored the ferroptosis-inducing ability of flubendazole on GBM cells. After treating glioma cell lines U251 and LN229 with the flubendazole (DMSO <1‰), cell viability was inhibited in a concentration-dependent manner (IC50 for LN229 = 0.5331 μM, IC50 for U251 = 0.6809 μM), attributed to the induction of ferroptosis, as evidenced by increased MDA levels, accumulation of ROS and lipid peroxides, change in mitochondrial membrane potential and structure. Protein analysis related to ferroptosis showed upregulation of TFRC, DMT1 and p53, alongside downregulation of xCT, FHC and GPX4 (p < 0.05). All-atom docking studies demonstrated that flubendazole bound closely with xCT, and TFRC, validating its role in inducing glioma ferroptosis via modulation of these proteins. Notably, flubendazole could damage the glioblastoma stem cells (GSC) that are typically resistant to other therapies, thereby possessing advantages in stopping glioma recurrence. This study delved into the mechanisms of flubendazole-induced ferroptosis in glioma, broadening its application and providing new ideas for new uses of other old drugs.

The Potential Health Risks of Catha edulis Forsk (Khat) Consumption on Some Vital Organs

Abstract Introduction/Objective Introduction: Catha edulis Forsk (Khat) leaves are widely chewed by adults in the Arabian Peninsula and the Horn of Africa for their mild stimulating properties. Objectives To investigate the impact of an aqueous extract of Catha edulis Forsk leaves on the proper functioning of vital organs. Methods/Case Report Methods: Materials and methods: Twenty-five female albino rats were divided into two groups: a control group and a treated group which received a daily gavage of 1 ml of aqueous Khat extract with a concentration of 700 mg/kg body weight for four weeks. The effects of this treatment on selected organs, including the brain, hippocampus, heart, and ovaries, were assessed using various measurements and analyses. Results (if a Case Study enter NA) Results: Results: The antioxidant evaluation showed a significant increase in MDA levels in the khat group and a significant decrease in GSH, SOD, and CAT levels compared to the control group. There was a significant decrease in IL-4 and a significant increase in TNF-α and TGF-β1 compared to the control group. In contrast, the cardiac enzymes; Troponin, CK, CPK, and GOT showed a significant increase compared to the control group. The results of the hormonal assay indicated a significant increase in LH, FSH, and testosterone levels, along with a significant decrease in estrogen in the khat group compared to the control group. Furthermore, the histological investigations revealed significant changes in tissue architecture in the studied organs. In the heart, the treated group exhibited an intact, thick pericardium, along with markedly apoptotic cardiac muscle fibers and others with pyknotic nuclei and mildly congested blood vessels and capillaries. The examination of brain tissues in the treated group showed thick meninges with mild inflammatory infiltrate, marked astrogliosis with degenerated neurons in the cerebral cortex, inflammatory infiltrate with abscess formation and mildly congested blood vessels and eosinophilic plaque-like area in the deep cortex, and scattered degenerated neurons and some neurons with nuclear vacuoles and average glial cells in the white matter. In the ovaries, sections showed primary, secondary, and antral follicles, scattered cystically dilated follicles with atrophied lining, and multiple corpora lutea in the edematous stroma with scattered apoptotic stromal cells. Conclusion Based on these findings, long-term use of khat as a chewing material may harm vital organs.

Curcumin promotes ferroptosis in hepatocellular carcinoma via upregulation of ACSL4

BackgroundFerroptosis, a novel iron-ion-dependent metabolic cell death mode with lipid peroxides as the main driving substrate, plays an irreplaceable role in the development and preventive treatment of hepatocellular carcinoma. Curcumin has potent pharmacological anti-tumor effects.Aim of the studyWe aimed to evaluate the ex vivo and in vivo cancer inhibitory activity of curcumin and its specific mechanism of action.Materials and MethodsWe used the hepatocellular carcinoma cell lines HepG2 and SMMC7721 to assess the direct inhibition of hepatocellular carcinoma proliferation by curcumin in vitro and a tumor xenograft model to evaluate the in vivo cancer inhibitory effect of curcumin.ResultsIn this study, we found that ferroptosis’s inhibitors specifically reversed the curcumin-induced cell death pattern in HCC. After curcumin intervention, there was a substantial increase in MDA levels and iron ion levels, and a decrease in intracellular GSH levels. Meanwhile, the expression of GPX4 and SLC7A11 was significantly reduced at the protein levels, while ACSL4 and PTGS2 expression was significantly increased.ConclusionsThis study showed that curcumin significantly decreased the proliferation of HCC cells and significantly increased the sensitivity of ferroptosis. These results suggest that ACSL4 is a viable target for curcumin-induced ferroptosis in treating HCC.

Neuroinflammation and oxidative redox imbalance drive memory dysfunction in adolescent rats prenatally exposed to Datura Stramonium

Although there have been reports indicating that Datura Stramonium (D. stramonium) may induce anticholinergic and neuropsychiatry effects, the compound is still being used for recreational and medicinal purposes while ingestion during pregnancy has been documented. Intriguingly, minimal studies have investigated the potential neurotoxic impact of D. stramonium exposure at various stages of gestation, including its potential implication on neurophysiological well-being later in life. The present study, therefore, examined spontaneous working memory and the expression of specific neurochemicals modulating crucial neural processes in adolescent rats exposed to high and low D. stramonium doses during different stages of gestation. Pregnant rats were orally infused with 150- or 500- mg/kg/day of D. stramonium either during mid- (second week; days 8–14) or late- (third week; days 15–21) gestation, while control rats received PBS at dosing periods. Behavioral characterization of offspring between postnatal days (PD) 40 and 41 in the Y-maze revealed that D. stramonium perturbed spatial working memory in rats, although locomotor activity was generally unaltered. In addition to SOD and nitric oxide downregulation, induction of oxidative stress in the hippocampus and prefrontal cortex (PFC) of young adult rats prenatally exposed to D. stramonium was corroborated by depletion of key antioxidant regulatory elements glutathione peroxidase, glutathione reductase and catalase, which was accompanied by lipid peroxidation shown by increased MDA levels. Whereas increased expression of acetylcholinesterase and LDH was seen in adolescent rats prenatally infused D. stramonium, acetylcholine levels were downregulated in both hippocampal and PFC lysates, suggesting cholinergic and metabolic dysfunctions. Immunohistochemical labelling of GFAP and IBA-1 revealed increased expression of reactive astrocytes and microglia respectively, while the accompanying TNFα upregulation in both the hippocampus (dentate gyrus) and PFC causally linked intrauterine D. stramonium exposure with neuroinflammatory responses postnatally. Overall, our data correlated postnatal spatial working memory dysfunction evoked by D. stramonium exposure during critical stages of embryonic development to oxidative redox impairment, cholinergic disruption and neuroinflammatory perturbations in rats.

Biochemical responses of crayfish exposed to imidacloprid: assessment of oxidative stress, osmoregulatory response and neurotoxicity

ABSTRACT Among the nicotinoid insecticides, imidacloprid (IMI) may affect non-target invertebrates like aquatic crustaceans by entering the aquatic environment through rainfall. Nevertheless, there are not sufficient studies on the toxicity mechanism of IMI in crayfish. Here, we investigated the effects of IMI on oxidative stress, osmoregulatory, and neurotoxicity biomarkers. The 96-hour lethal concentration value (96 h-LC50) of IMI was determined to be 0.932 mg AI L−1. Four concentrations of IMI (0.932, 0.466, 0.233 and 0.117 mg AI L−1) were applied to crayfish for 96 h. Na+/K+-ATPase, Mg2+-ATPase, Ca2+-ATPase, and total ATPase activities had almost significantly concentration-related inhibition in both gill and muscle tissues (p < 0.05). Compare with control in hepatopancreas, the activities of GST, SOD and GPx were increased, while the activities of AChE, CES and GR were decreased (p < 0.05). As non-enzymatic parameters, a statistically significant (p < 0.05) increase in MDA levels and a decrease in GSH levels were observed in the hepatopancreas compared to the control group, which was not related to the concentration. In conclusion, it can be said that the study's biomarkers are highly helpful and that commercially consumed crayfish are a significant non-target organism in the assessment of IMI toxicity.

Neuroprotective Effects of Bryophyllum pinnatum against Ketamine-Induced Neurotoxicity in Wistar Rats: Neurochemical, Oxidative Stress, and Histological Investigation

Background: This study evaluated the neuroprotective effects of Bryophyllum pinnatum (B. pinnatum) in ketamine-induced neurotoxicity in Wistar rats, focusing on neurochemical and oxidative stress markers, as well as histological changes in the hippocampus and cerebral cortex. Methods: Sixty male Wistar rats were divided into six groups. Group 1 received normal saline (2ml), Group 2 was administered ketamine (20mg/kg), and Group 3 received risperidone (0.5mg/kg). Groups 4, 5, and 6 were treated with B. pinnatum at 50mg/kg, 100mg/kg, and 200mg/kg, respectively for a duration of 21 days after induction of toxicity. Neurochemical markers (dopamine, glutamate, GABA, serotonin, noradrenaline, acetylcholine), oxidative stress markers (GSH, MDA, SOD, CAT, GPx), and histological analysis of brain tissues were evaluated after treatment periods of one, two, and three weeks. Results: Ketamine administration significantly reduced dopamine, GABA, serotonin, and noradrenaline levels while increasing acetylcholine and glutamate levels (p&lt;0.05). B. pinnatum treatment reversed these effects in a dose-dependent manner, particularly at high doses. Oxidative markers showed reduced GSH and increased MDA levels with ketamine, which B. pinnatum mitigated significantly (p&lt;0.05). Histologically, ketamine caused neuronal degeneration and microstructural distortion in the hippocampus and cerebral cortex, which were markedly reduced by B. pinnatum, especially at 200mg/kg, showing well-preserved neuronal structures. Conclusion: B. pinnatum demonstrates significant neuroprotective effects against ketamine-induced neurotoxicity by modulating neurochemical and oxidative markers and preserving histological integrity in brain tissues, suggesting its potential therapeutic application in neurotoxic conditions.

Coconut oil affects aging-related changes in Mongolian gerbil liver morphophysiology

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.

Tannin-Rich Fraction of Cyperus esculentus Protects against Lead-Induced Testicular Toxicity in Male Wistar Rats through ITS Antioxidant Properpty

Aims: Lead as a common environmental toxic metal, causes many histological, physiological and biomedical abnormalities in human and animals. This study evaluated the antioxidant potential of tannins on serum level of testosterone, LH and FSH and histology of the testes of male Wistar rats. Materials and Methods: Twenty-five adult male Wistar rats were divided into five (5) groups, (n=5). Group NS was administered normal saline only, Group PBO was administered with 30mg/kg body weight (BW) of lead, group LDTPB was administered with 50 mg/kg BW of tannins and 30mg/kg BW of lead, group MDTPB was administered with 100mg/kg BW of tannins and 30mg/kg BW of lead, group HDTPB was administered 150mg/kg BW of tannins and 30mg/kg BW of lead orally for 28 days. The animals were sacrificed and testes were harvested on day 29 of the experiment and histological and histochemistry studies done using the H&amp;E and VVG staining respectively. Sperm parameters (motility, concentration), sex hormones (Testosterone, LH, FSH) and antioxidant activities were also determined. Results: There was Leydig cell proliferation and an increase series of spermatogenesis of the testes in the rats of groups administered with lead and tannins different doses (LDTPB, MDTPB and HDTPB) when compared with rats administered with lead only. Rats in groups LDTPB, MDTPB and HDTPB had a significant increase in levels of serum testosterone (p&lt;0.05) when compared with positive control group (2). There was increase in levels of FSH in MDTPB and HDTPB groups when compared with positive control (2). Increased MDA levels were observed in the rats given lead only, PBO when compared to NS group. The rats given lead and tannins significant growth of seminiferous epithelium, improved sperm quality, and had decreased MDA levels. Conclusion: This study demonstrated the protective role of tannins fraction of Cyperus esculentus on lead-induced testicular toxicity in male Wistar rats.

Insights into the response mechanisms of Tetradesmus obliquus to aged polylactic acid and tetracycline exposure via transcriptome analysis and physiological evaluations

Microplastics (MPs) and antibiotics, identified as emerging pollutants, are extensively prevalent in aquatic environments and display prolonged durability. Unlike conventional plastics, biodegradable plastics are more susceptible to decomposition in the environment, resulting in the generation of microplastics and posing potential risks to the aquatic ecosystems. In this study, we assessed growth inhibition, chlorophyll a content, malondialdehyde content (MDA), and antioxidant enzyme activities. These measurements were integrated with transcriptome analysis to explore the response mechanisms of virgin and aged polylactic acid (vPLA and aPLA) and tetracycline (TC) following 14-day exposure to Tetradesmus obliquus, either individually or in combination. The findings indicated that exposure to vPLA did not significantly impact the growth of T. obliquus. Conversely, aPLA demonstrated growth-promoting effects on T. obliquus, particularly in the latter incubation stages. Moreover, a 14-day exposure significantly increased the chlorophyll a content and the activities of superoxide dismutase (SOD), catalase glutathione (CAT) and glutathione S-transferase (GST) within the algal cells. Apart from 1 mg L−1, the TC concentrations of 2.5, 5.0, and 10 mg L−1 exhibited significant toxic effects on T. obliquus, including growth inhibition, decreased chlorophyll a content, elevated activities of SOD, CAT, and GST, and increased MDA levels. Exposure to a combination of 300 mg L−1 aPLA and 5.0 mg L−1 TC, compared to solely 5 mg L−1 TC, demonstrated a notable reduction in TC toxicity to T. obliquus in the presence of aPLA. This was indicated by elevated algal cell density and chlorophyll a content, as well as a decrease in MDA content. Transcriptome analysis indicated an enrichment of differentially expressed genes (DEGs) in pathways linked to porphyrin metabolism, photosynthesis, carbon fixation, and metabolism within the aPLA + TC combined exposure. The study aid in expanding our knowledge of the potential ecological risks posed by biodegradable plastics and accompanying pollutants in aquatic environments.

Aged fragmented-polypropylene microplastics induced ageing statues-dependent bioenergetic imbalance and reductive stress: In vivo and liver organoids-based in vitro study

Ageing is a nature process of microplastics that occurrs daily, and human beings are inevitably exposed to aged microplastics. However, a systematic understanding of ageing status and its toxic effect is currently still lacking. In this study, plastic cup lids-originated polypropylene (PP) microplastics were UV-photoaged until the carbonyl index (CI), a canonical indicator for plastic ageing, achieved 0.08, 0.17, 0.22 and 0.28. The adverse hepatic effect of these aged PPs (aPPs) was evaluated in Balb/c mice (75 ng/mL water, about 200 particles/day) and human-originated liver organoids (LOs, 50 particles/mL, ranged from 5.94 to 13.15 ng/mL) at low-dose equivalent to human exposure level. Low-dose of aged PP could induce hepatic reductive stress both in vitro and in vivo, by elevating the NADH/NAD+ratio in a CI-dependent manner, together with hepatoxicity (indicated by increased AST secretion and cytotoxicity), and disrupted the genes encoding the nutrients transporters and NADH subunits accompanied by the restricted ATP supply, declined mitochondrial membrane potential and mitochondrial complexI/IV activities, without significant increase in MDA levels in the liver. These changes in the liver disrupted systematic metabolism, representing a circulatory panel of increases in the lactate, triglyceride, Fgf21 levels, and decreases in the pyruvate level, linked the reductive stress to the declined body weight gain but elevated hepatic NADH contents following aPPs exposure. Additionally, assessing by the LOs, it was found that digestion drastically accelerated the ageing of aPPs and worsen the energy supply upon mitochondria, representing a “scattergun effect” induced by the formation of micro- and nano-plastics mixture toward NADH/NAD+imbalance.

Indole-3-acetic acid exposure leads to cardiovascular inflammation and fibrosis in chronic kidney disease rat model

Indole-3-acetic acid (IAA), a protein-bound uremic toxin, has been linked to cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study explores the influence of IAA (125 mg/kg) on cardiovascular changes in adenine sulfate-induced CKD rats. HPLC analysis revealed that IAA-exposed CKD rats had lower excretion and increased circulation of IAA compared to both CKD and IAA control groups. Moreover, echocardiography indicated that CKD rats exposed to IAA exhibited heart enlargement, thickening of the myocardium, and cardiac hypertrophy in contrast to CKD or IAA control group. Biochemical analyses supported the finding that IAA-induced CKD rats had elevated serum levels of c-Tn-I, CK-MB, and LDH; there was also evidence of oxidative stress in cardiac tissues, with a significant decrease in SOD and CAT levels, as well as an increase in MDA levels. The gene expression analysis found significant increases in ANP, BNP, β-MHC, TNF-α, IL-1β, and NF-κB levels in IAA-exposed CKD groups in contrast to the CKD or IAA control group. In addition, higher cardiac fibrosis markers, including Col-I and Col-III. The findings of this study indicate that IAA could trigger cardiovascular inflammation and fibrosis in CKD conditions.

Alliin mitigates the acute kidney injury by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

Acute kidney injury (AKI) is a clinical syndrome that is characterized by a sudden loss of kidney function, leading to severe metabolic disorders, multiple organ failure, and even death. Recent studies have strengthened the evidence for ferroptosis in AKI development. Alliin, a sulfur-containing amino acid with multiple pharmacological functions, was claimed with promising antioxidant and anti-inflammation effects in protecting organ damages. Herein, Alliin's potential in AKI treatment was investigated by exploring its impact on ferroptosis, providing a new strategy for clinical AKI treatments. Cecal ligation and puncture (CLP) modeling was performed on rats, followed by treated with 7.5 and 15mg/kg/day of alliin for 6days. A declined survival rate, severe renal pathological changes, renal dysfunction, and enhanced inflammatory state were observed in CLP-treated rats, which were remarkably alleviated by alliin. Moreover, increased MDA levels, declined SOD activity, and downregulated Nrf2, GPX4, and xCT in CLP-treated rats were notably reversed by alliin. To explore potential mechanisms of alliin, NRK-52E cells were stimulated with 1μg/mL LPS for 24h, followed by culturing with 30 and 100μM of alliin for 24h. Reduced cell viability, enhanced apoptosis, increased ROS production, boosted MDA level, and declined SOD activity were observed in LPS-stimulated NRK-52E cells, accompanied by downregulated Nrf2, GPX4, and xCT, which were strikingly ameliorated by alliin. Additionally, the influence of alliin on cell viability, oxidative stress (OS), and ferroptosis in LPS-stimulated NRK-52E cells were markedly abolished by silencing Nrf2. Collectively, alliin mitigated AKI by suppressing ferroptosis via regulating the Nrf2/GPX4 axis.

Protective Effects of Syringic Acid Against Oxidative Damage, Apoptosis, Autophagy, Inflammation, Testicular Histopathologic Disorders, and Impaired Sperm Quality in the Testicular Tissue of Rats Induced by Mercuric Chloride.

Mercury (Hg) is one of the most toxic heavy metals that damage testicular tissue. Mercury chloride (HgCl2) is one of the most toxic forms of mercury that can easily cross biological membranes. Syringic acid (SA) is a natural flavonoid found in many vegetables and fruits. In this study, the effects of SA against HgCl2-induced testicular damage in rats were determined by biochemical, histopathological, and spermatological analyses. For this study, a total of 35 Spraque Dawley rats were used. Rats were divided into five groups as control, HgCl2, SA 50, HgCl2 + SA 25, and HgCl2 + SA 50. HgCl2 was administered intraperitoneal (IP) at a dose of 1.23 mg/kg/bw, while SA was administered by oral gavage at doses of 25 and 50 mg/kg/bw. The rats were then sacrificed, and testicular tissues were removed. HgCl2 caused an increase in MDA level and a decrease in SOD, CAT, and GPx activity and GSH level in the testicular tissue of rats. HgCl2 is involved in the increase of eIF2-α, PERK, ATF-4, ATF-6, CHOP, NF-κB, TNF-α, IL-1β, Apaf-1, Bax, and Caspase-3 mRNA expression. HgCl2 caused a decrease in sperm motility, an increase in the rate of abnormal sperm and sperm DNA fragmentation in rats. However, SA oral administration dose-dependently inhibited endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis and preserved epididymal sperm quality and testicular histoarchitectures. In conclusion, SA had protective effects against HgCl2-induced testicular oxidative damage, inflammation, endoplasmic reticulum stress, and apoptosis.

Studies on the ameliorative potential of Rheum webbianum rhizome extracts on 1,2-dimethylhydrazine (DMH) induced colorectal cancer and associated hepatic and haematological abnormalities in swiss albino rats

Ethnopharmacological relevanceRheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. Aim of the studyThis study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. Materials and methodsFour types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. ResultsCell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml. Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. ConclusionThis study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.

The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.

Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality

In this study, it was aimed to determine the effect of sinapic acid (SNP), a polyphenol with antioxidant, anti-inflammatory and antibacterial properties, on testicular damage caused by vancomycin (VCM), a widely used antibiotic against gram positive bacteria. A total of 35 male Sprague Dawley rats were used in the study, divided into five groups: control, VCM, SNP, VCM + SNP 10, and VCM + SNP 20. Following a week of oral administration, the rats were euthanized under sevoflurane anesthesia. While the VCM group had a significant increase in MDA levels, the SNP administration inhibited the increase in MDA levels. VCM led to a significant decrease in GSH levels, SOD, CAT, and GPx activity in the testicular tissue of rats, while SNP administration increased these antioxidant levels. SNP administration decreased the mRNA expression levels of VCM induced Nrf-2, HO-1, and NQO1 in testicular tissue while increasing the levels of MAPK14, MAPK15, JNK, P53, Apaf-1, Caspase-3, Caspase-6, Caspase-9, and Beclin-1 mRNA transcript levels. The VCM group showed a significant increase in Bax and NF-κB levels in testicular tissue, while Bcl-2 levels decreased. VCM significantly decreased sperm motility and increased the percentage of damaged sperm in rats. Histopathological results revealed that VCM caused disruption of basement membranes and disorganization of seminiferous tubules, but SNP administration preserved testicular histology. As a result, VCM increased oxidative stress, apoptosis, and autophagy in the testicular tissue of rats, altered testicular histopathology, and decreased sperm quality, while SNP decreased these effects.

Cardioprotective effect of CB1 receptor antagonist AM251 against β receptor-stimulated myocardial infarction via modulation of NF-kB signaling pathway in diabetic mice

We substantiated the effect of AM251, a cannabinoid receptor-1 (CB1R) antagonist, against β-receptor stimulated myocardial infarction (MI) in streptozotocin (STZ)-induced diabetic mice via modulation- of the NF-kB signaling pathway. The different parameters were assessed such as ECG, hemodynamic, cardiac injury markers, oxidative stress parameters, pro-inflammatory cytokines, and histopathological abnormalities. Mice were fed a high-fat diet for 30 days. On day 7, to trigger diabetes, 150 mg/kg of STZ was injected intraperitoneally. On day 10, to determine whether diabetes developed, the blood level of glucose was monitored. From days 11–30, diabetic mice were injected with either CB1R agonist oleamide or antagonist AM251 or both, with concurrent administrations of β-agonist isoproterenol on days 28 and 29 to induce MI. In comparison to normal, the myocardial infarcted diabetic animals demonstrated alterations in ECG, hemodynamic profiles, and diminished enzymatic activities (CK-MB, LDH, SOD, GSH, catalase), with concurrently increased MDA levels, which indicated increased oxidative stress in the myocardium. Additionally, higher concentrations of cytokines that signal myocardial inflammation, such as IL-1β, IL-6, and TNF-α, were also noted. Furthermore, elevated myonecrosis, edema, and cell infiltration which is confirmed by histopathology of heart tissue. Treatment with AM251 significantly ameliorated myocardial redox status, reduced cytokines, and repaired enzymatic activities leading to subsequent recovery in cardiac function. AM251 effectively suppressed myonecrosis and edema. This study also showed that AM251 protects against myocardial inflammation and oxidative stress triggered by isoproterenol by blocking NF-kB signalling pathway. However, upregulation of the CB1R through oleamide showed significant cardiac toxicity. Conversely, the concurrent administration of oleamide and AM251 failed to induce cardiotoxic effects in isoproterenol-induced MI in diabetic mice which indicates downregulation of the CB1R might be associated with the cardioprotective effect.