Archives of Toxicology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 27, 2024
Язык: Английский
Journal of Biochemical and Molecular Toxicology, Год журнала: 2024, Номер 38(10)
Опубликована: Сен. 20, 2024
Abstract Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, found abundantly in plants. This study evaluated the protective of esculetin against DOX‐induced hepatotoxicity rat livers. Forty‐eight rats were randomly divided into six groups with eight each group: control (I), DOX (II), (III, 50 mg/kg), (IV, 100 DOX+esculetin (V, and (VI, mg/kg). The administration effectively mitigated alterations measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that treatment significantly reduced Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, Casp9 while increasing Foxo3 . These findings suggest esculetin, antioxidant anti‐inflammatory effects, might be therapeutic option for protecting hepatotoxicity.
Язык: Английский
Процитировано
8
PeerJ, Год журнала: 2024, Номер 12, С. e17094 - e17094
Опубликована: Март 29, 2024
Liver disease is a common and serious threat to human health. The progression of liver diseases influenced by many physiologic processes, including oxidative stress, inflammation, bile acid metabolism, autophagy. Various factors lead the dysfunction these processes basing on different pathogeny, pathology, clinical manifestation, pathogenesis, are grouped into categories. Specifically, Sirtuin1 (SIRT1), member sirtuin protein family, has been extensively studied in context injury recent years confirmed significant role disease. SIRT1 found play critical regulating key injury. Further, seems cause divers outcomes types diseases. Recent studies have showed some therapeutic strategies involving modulating SIRT1, which may bring novel target. To elucidate mechanisms underlying sirtuin1 its potentiality as target, this review outlines signaling pathways associated with injury, discusses advances targeting
Язык: Английский
Процитировано
5
Pharmacognosy Magazine, Год журнала: 2025, Номер unknown
Опубликована: Янв. 5, 2025
Background Hyperoside is a potential liver cell and mitochondrial protector, but there no evidence to suggest that hyperoside can effectively treat doxorubicin (DOX) related toxicity. Purpose This study aims determine the role of in DOX toxicity damage vivo vitro. Methods A mouse model was induced by intraperitoneal injection DOX, administered orally for treatment. During this period, weight food intake mice were recorded. The morphology tissue observed hematoxylin eosin staining. Oxidative stress inflammatory status through serum factors oxidative markers. Mitochondrial determined degree DNA damage. Western blotting reverse transcription polymerase chain reaction (RT-PCR) used detect expression pyroptosis genes cells. Results DOX-induced status, function damage, hepatocyte necrosis mice. Further research suggests beneficial effect achieved inhibiting Conclusion indicates improves
Язык: Английский
Процитировано
0
Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 14, 2025
Abstract Doxorubicin (DOX) is a highly potent broad-spectrum anticancer drug, but it has severe side effects, including hepatotoxicity. Therefore, we evaluated the efficacy of febuxostat (FBX), specific inhibitor xanthine oxidase and antioxidant, in blocking hepatotoxicity associated with DOX rats. Rats were treated FBX (10 or 15 mg/kg/day orally for 2 weeks) given (15 mg/kg as single dose at 7th day, intraperitoneal) to induce The results indicated that could reduce pathological alterations liver tissues induced by ameliorate inappropriate changes function biomarkers (AST, ALT, ALP) serum, oxidative stress parameters (catalase, superoxide dismutase, NOX1, NQO-1, HO-1, Keap-1, Nrf2) inflammatory markers (NF-κB p65, TNF-α, NLRP3). Additionally, attenuated p53, BAX, cytochrome C, caspase-9, caspase-3 levels restrain cell apoptosis. In addition, therapy was found increase protein SIRT-1 AMPK liver. These findings demonstrate can caused rats through mechanisms counteract stress, inflammation,
Язык: Английский
Процитировано
0
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 24, 2025
Doxorubicin (DOXO) is a powerful anthracycline chemotherapeutic drug, but its clinical usage has been limited by deleterious effects on different organs, particularly hepatotoxicity. The aim of this study was to establish the combined aerobic interval training (AIT) and curcumin supplementation mitigating oxidative damage endoplasmic reticulum (ER) stress-mediated apoptosis in rat model DOXO-induced Fifty-six male Sprague–Dawley rats were randomly split into six groups: control (CON), vehicle, doxorubicin (Dox), + (Dox-C), AIT (Dox-A), (Dox-AC). DOXO intraperitoneally injected weekly (4 mg/kg/week) for five weeks. Curcumin (100 mg/kg/day) min at 80–90% VO2max intermitted 3 active rest 65–75% VO2max) conducted times week Finally, hepatic tissue blood samples collected assess histopathological changes, liver biomarkers, protein expression stress, ER markers. Tissue sections revealed that significantly improved hepatotoxicity induced DOXO, as evidenced positive alterations serum markers (P < 0.05). Both reduced DOXO-triggered damage, 0.05), with latter showing slightly higher effectiveness. Consequently, combination exhibits protective against chronic demonstrating relatively greater efficacy increasing antioxidant capacity reducing stress apoptosis.
Язык: Английский
Процитировано
0
Future Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 11(1)
Опубликована: Апрель 14, 2025
Abstract Background Doxorubicin (DOX) has long been a foundational drug in cancer therapeutics. Despite its proven efficacy, the persistent challenge of mitigating associated side effects, notably hepatotoxicity and neurotoxicity, underscores necessity for intervention. Luteolin (LUT) is naturally derived flavonoid with spectrum bioactive characteristics, involving anti-apoptotic, antioxidant, anti-inflammatory, anti-cancer attributes. This study investigates possible protective effect LUT against DOX-induced focusing on modulation endoplasmic reticulum (ER) stress pathways miRNA 199a- 5p expression. Forty-eight male Sprague Dawley rats were assigned to six groups: control, (200 mg/kg), DOX (3.5 mg/kg, i.p.) administered twice per week 3 weeks, three treatment groups that received daily oral gavage at doses 50, 100, 200 mg/kg weeks alongside DOX. Results Behavioral assessments revealed best improvements co-treated high dose paralleled by mitigation neurodegeneration cortex hippocampal areas brain. The hepatoprotective mg/kg) demonstrated notable decrease liver enzymes restoration hepatocytic architecture, coupled upregulation miRNA-199a-5p suppression glucose-regulated protein 78 (GRP78). inhibited ER via suppressing inositol-requiring enzyme 1 alpha (IRE1α)/protein kinase R-like (PERK)/eukaryotic initiation factor 2 (eIF2α)/activating transcription 6 (ATF6) axes, thereby inhibiting apoptosis. Conclusions efficacious alleviating hepatic injury neurotoxicity dampening pathways. Graphical abstract
Язык: Английский
Процитировано
0
PLoS ONE, Год журнала: 2024, Номер 19(9), С. e0310364 - e0310364
Опубликована: Сен. 12, 2024
Each year thousands of people suffer across the globe due to higher cancer incidence and mortality rates. Additionally, treatment option for patients is also costly, often drugs from lower efficacy with more side effects. The DNA topoisomerase can function as an established target because Human Topoisomerase (Top1) regulates genetic transcription during post-mitotic phase plays a critical role in supercoiling replication repair. Therefore, drug therapy, blocking Top1 may be crucial inhibiting proliferation cells. Here, TCM (traditional Chinese medicine) compounds have been screened through virtual screening. medicine library’s screening process made it possible narrow down compound list 29 based on binding energy (-7.1 -9.3Kcal/mol), while following Lipniski filtering, MM/PB (GB) SA filtering was used screen remaining 22 top four were chosen free energy. compounds; CID-65752 (T2972: Rutaecarpine), CID-5271805 (T4S2126: Ginkgetin), CID-9817839 (T2S2335: Dehydroevodiamine) CID-51106 (T3054: Daurisoline) had comparatively -8.2, -8.5, -8.3 -8.2 respectively molecular docking than other compounds. Among these compounds, no toxic profile two found ADMET filtering. Moreover, SASA (solvent accessible surface area), Rg (radius gyrations), RMSD (root mean square deviation), RMSF fluctuation) drug-protein complex reveals stability rigidity dynamics simulation study. However, studies need validated experimental approaches develop potent effective drugs.
Язык: Английский
Процитировано
3
Tissue and Cell, Год журнала: 2023, Номер 84, С. 102182 - 102182
Опубликована: Июль 26, 2023
Язык: Английский
Процитировано
8
Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2023, Номер 397(6), С. 3897 - 3906
Опубликована: Ноя. 16, 2023
Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness using natural materials as chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential renal syndrome protection. five equal groups fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while II got an intraperitoneal injection doxorubicin (18 mg/kg bwt). Group III CBD (26 bwt) IV 1 ml and V trimetazidine (10 bwt), addition a single dose on 11th day both (IV, V). administration led noticeable improvement oxidative stress parameters (SOD GSH) by significantly lowering enzyme activity (ALT AST), well serum creatinine urea, IL-6, MDA, confirming anti-inflammatory accuracy linked significant IL6R DNA frequency concentration line with histopathology results. As result its antioxidant capabilities, may have protective quality, medication could be related controlling problems.
Язык: Английский
Процитировано
8
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 277, С. 134135 - 134135
Опубликована: Июль 26, 2024
Язык: Английский
Процитировано
1