Protective effects of herbal compounds against cyclophosphamide-induced organ toxicity: a pathway-centered approach

Drug and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 43

Published: Jan. 23, 2025

Cyclophosphamide is a key component of numerous chemotherapeutic protocols, demonstrating broad-spectrum efficacy against various malignancies and non-cancerous conditions. This review examines CPM's metabolic pathways, therapeutic applications, its resulting organ-specific toxicities. Despite clinical benefits in treating nephrotic syndrome, encephalomyelitis, breast cancer, ovarian other diseases, CPM associated with significant adverse effects on the kidneys, liver, heart, lungs, intestines. The discussion delves into molecular mechanisms underlying these toxicities, highlighting dysregulation signaling including Nrf2, NF-κB, MAPK/ERK, AKT. In addressing challenges, recent studies have identified herbal drugs phytochemicals capable mitigating CPM-induced toxicity. Notable compounds such as cinnamaldehyde, baicalin, quercetin, curcumin demonstrated protective effects. Integrating formulations therapy proposed to enhance patient safety treatment efficacy. underscores influence apoptosis inflammation which lead alterations biomarkers. Phytochemicals may exert by restoring disrupted pathways normalizing altered compilation presented this serves valuable resource for researchers exploring products potential A gap current literature lack trials evaluating that mitigate toxicity vivo. Rigorous are necessary establish cancer treatment. Such research will clarify role natural remedies complementing conventional therapies, ultimately improving outcomes.

Language: Английский

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Phytochemicals as Potential Lead Molecules against Hepatocellular Carcinoma

Current Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 31(32), P. 5199 - 5221

Published: Jan. 12, 2024

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, accounting for 85-90% cancer cases and a leading cause cancer-related mortality worldwide. The major risk factors HCC include hepatitis C B viral infections, along with chronic diseases, such as cirrhosis, fibrosis, non-alcoholic steatohepatitis associated metabolic syndrome. Despite advancements in modern medicine, there continuous rise annual global incidence rate HCC, it estimated to reach >1 million by 2025. Emerging research phytomedicine chemotherapy has established anti-cancer potential phytochemicals, owing their diverse biological activities. In this review, we report phytochemicals that have been explored combating hepatocellular possess great be used an alternative or conjunction existing treatment modalities. An overview pre-clinical observations, mechanism action molecular targets some these also incorporated.

Language: Английский

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Capsaicin Ameliorates the Cyclophosphamide-Induced Cardiotoxicity by Inhibiting Free Radicals Generation, Inflammatory Cytokines, and Apoptotic Pathway in Rats

Life, Journal Year: 2023, Volume and Issue: 13(3), P. 786 - 786

Published: March 14, 2023

Cyclophosphamide is an antineoplastic agent that has a broad range of therapeutic applications; however, it numerous side effects, including cardiotoxicity. Furthermore, chili peppers contain substance called capsaicin, having antioxidant and anti-inflammatory effects. Thus, this research paper focuses on the potential mechanism capsaicin's cardioprotective activity against cyclophosphamide-induced cardiotoxicity by measuring expression oxidative inflammatory marker such as interleukins caspases. The following groups rats were randomly assigned: only vehicle given for 6 days (control group); cyclophosphamide 200 mg/kg intraperitoneal 4th day (positive control capsaicin 10 orally followed treatment; 20 six maximum amount alone (20 mg/kg) days. Using ELISA kits, was found administration significantly increased levels lactate dehydrogenase, troponin-I (cardiac cell damage marker), lipid peroxidation, triglyceride, interleukin-6, tumor necrosis factor-alpha, caspase 3. However, markedly reduced enzymes catalase glutathione levels. Both doses could reverse cardiac markers, shown significant decline in (lactate dehydrogenase troponin-I). In addition, cytokine (interleukin-6 factor-alpha), 3, triglycerides. treatment raised content catalase. capsaicin-treated group restored parameter's imbalance generated considerable protection cardiomyocyte harm from male Wistar rats. These protective effects might be beneficial negative impacts when used to treat cancer immune-mediated diseases.

Language: Английский

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Histopathological and Biochemical Assessment of Morin Hydrate’s Protective Role against Cyclophosphamide-Induced Multi Organ Toxicity

Toxicology International, Journal Year: 2025, Volume and Issue: unknown, P. 111 - 128

Published: March 12, 2025

Cyclophosphamide, an extensively used antineoplastic drug, exhibits therapeutic efficacy. However, it is associated with a significant number of side effects, reproductive toxicity being the most severe effect. In this study, we examined potential effects morin hydrate, bioactive flavonoid multiple pharmacological properties, on organ damage caused by cyclophosphamide in male rats. The rats were divided into four groups: Sham, CYP control, MH per se, and CYP+MH. Cyclophosphamide was administered intraperitoneally at dose 40 mg/kg days 0, 7, 14, 21, 28 hydrate (100 body weight, PO route daily for groups 3 4). On 29th day, euthanized, liver, lung, intestinal samples collected evaluation. Parameters such as relative serum markers, haematological parameters, antioxidant levels, histopathological examination to evaluate damage. control group showed decrease liver Total Erythrocyte Count (TEC), Leukocyte (TLC), Haemoglobin (Hb), Packed Cell Volume (PCV), lymphocytes, while exhibiting increased lung neutrophils, monocytes, eosinophils, Aspartate Transaminase (AST), Alanine (ALT), Alkaline Phosphatase (ALP) levels. Oxidative stress Malondialdehyde (MDA), elevated, Superoxide Dismutase (SOD) activity reduced glutathione (GSH) concentration decreased lungs, intestines group. Histopathological revealed marked congestion, infiltration mononuclear cells, alveolar damage, hyperplasia Type II pneumocytes lungs; pyknotic nuclei, vacuolar degeneration, necrosis liver; mucosal ulceration, degenerated villi, epithelial degeneration intestine. contrast, CYP+MH improvements weights, enzymes, oxidative histopathology compared These findings suggest that effectively counteracts CYPinduced rats, possibly due its free radical scavenging properties. Major Findings: study found cyclophosphamide-induced Specifically, treatment improved hematological tissue alone. protective are likely hydrate's

Language: Английский

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Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4838 - 4838

Published: May 19, 2025

Chemotherapy-induced renal encephalopathy (RE) is a disease characterized by cognitive impairment of the brain caused impaired kidney function for which there no definitive treatment. Icariin (ICA), main active component Epimedium, has good nervous system protection and anti-neuroinflammation effect, but its effect on injury insufficiency as result chemotherapy remains unclear. In this study, we demonstrated that 100 mg/kg ICA can not only successfully interface with serotonin regulate hormone levels also ameliorates damage in cyclophosphamide (CTX)-induced RE mouse models inhibits inflammation, oxidation, apoptosis regulating NF-κB, keap1-Nrf2, pathways. order to further study protective RE, used CTX-induced HT22 HEK293 cell models, intervention showed could prevent expression apoptosis-related proteins caspase-3, Bcl-2, Bax BDNF. Overall, our provides basis investigation therapeutic potential treatment neurodegenerative diseases context dysfunction, studies are needed at later stage fully elucidate underlying molecular mechanisms.

Language: Английский

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Capsaicin: a spicy way in liver disease

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 30, 2024

The incidence of liver disease continues to rise, encompassing a spectrum from simple steatosis or non-alcoholic fatty (NAFLD) steatohepatitis (NASH), cirrhosis and cancer. Dietary habits in individuals with may significantly impact the treatment prevention these conditions. This article examines role chili peppers, common dietary component, this context, focusing on capsaicin, active ingredient peppers. Capsaicin is an agonist transient receptor potential vanilloid subfamily 1 (TRPV1) has been shown exert protective effects diseases, including injury, NAFLD, fibrosis These are attributed capsaicin's anti-oxidant, anti-inflammatory, anti-steatosis anti-fibrosis effects. reviewed different molecular mechanisms effect capsaicin diseases.

Language: Английский

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"Yajieshaba" prevents acute alcoholic liver injury and repairs the intestinal mucosal barrier

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 318, P. 116921 - 116921

Published: July 23, 2023

An essential factor related to the acute alcoholic liver injury is damage intestinal mucosal barrier. Yajieshaba (YJSB) a commonly used formulation of Dai people in China and protects liver.This study investigated whether YJSB can prevent by regulating barrier.The mice received 0.39 g/kg, 1.17 3.51 g/kg dose for 7 days, mouse model was established single instillation 56% alcohol. Plasma biochemical markers were analyzed, identified histopathology, lipopolysaccharide (LPS), nuclear factor-k-gene binding (NF-κB), hepatic inflammatory factors, oxidative stress factors reactive oxygen species (ROS) content analyzed. The morphological changes histology observed H&E staining, ultrastructure ileal cells transmission electron microscopy. Immunofluorescence Western blot determine expression levels transporters enzymes involved Claudin 1, Occludin zona occludens 1 (ZO-1) homeostasis intestine.The findings showed that reduced aspartate aminotr ansferase (AST), alanine aminotransferase (ALT) total bile acid (TBA), both which are indicators function had protective effect against injury. In homogenate, level LPS, NF-κB, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) interleukin-6 (IL-6), decreased superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) catalase (CAT) ROS. results hematoxylin eosin (H&E) staining microscopy analysis revealed degree tissue intracellular organelles, implying reduce "attack factor" causes barrier damage, increase "defense immunohistochemistry blotting could claudin occludin, ZO-1 proteins, suggesting mechanism action alcohol involves upregulation barrier-related proteins repair damaged barrier.YJSB block other harmful substances blood protect resisting

Language: Английский

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Protective Effect and Mechanism of L‐Theanine on Acute Alcoholic Liver Injury in Mice

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Scope Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L‐theanine (LTA), compound found in tea leaves, mitigates the AALI‐induced oxidative stress and inflammation. However, its relationship with alcohol metabolism liver‐protective mechanism remains unexplored. Methods results This study investigates protective mechanisms of LTA against AALI mice. The demonstrate that tissue damage reduces serum levels aspartate aminotransferase alanine aminotransferase, triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor‐α, interleukin‐6, interleukin‐1β. enhances activity ethanol‐metabolizing enzymes decreases ethanol acetaldehyde levels. Mechanistically, accelerates upregulating hepatic expression ADH6, ALDH1B1, ALDH2, CAT, ACSS1 mRNA protein mice, downregulates CYP2E1 promoting antioxidative activities thus reducing accumulation ROS. attenuated inflammation inhibiting phosphorylation nuclear factor‐kappa B inhibitor alpha (IκBα) downregulating NF‐κB p65, TNF‐α, IL‐1β, IL‐6 mRNA, protein. Conclusion beneficial dietary supplement protects modulating TNF‐α/NF‐κB pathway.

Language: Английский

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Cyclophosphamide-induced multiple organ dysfunctions: unravelling of dose dependent toxic impact on biochemistry and histology

Toxicology Research, Journal Year: 2024, Volume and Issue: 13(6)

Published: Nov. 5, 2024

Abstract Background: Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated. Aim: This study aimed investigate dose dependent impact of cyclophosphamide liver, kidney, brain testis emphasizing serum tissue biochemical histological alterations. Materials methods: Experimental design consisted five groups albino rats. Group 1–5 were administered vehicle for consecutive days. On 6th day, group 1 received only termed as control; 2–5 through intraperitoneal route at the rate 50, 100, 150 200 mg/kg dose, respectively. After 24 h last administration, rats euthanised; biochemistry; histology, sperm count motility performed. Results: Serological, indices exhibited deviations from their regular status a marker toxicity in testis. Tukey’s HSD post hoc test revealed maximum damage with cyclophosphamide.

Language: Английский

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Atorvastatin protects against cyclophosphamide-induced thyroid injury in rats via modulation of JNK/ ERK/ p38 MAPK signaling pathway

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 111061 - 111061

Published: Oct. 14, 2023

Language: Английский

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