BMC Pharmacology & Toxicology最新文献

Background: Doxorubicin (Dox) is a highly effective chemotherapy drug used to treat various cancers. However, its clinical application is limited by liver toxicity, which is mainly caused by oxidative stress, inflammation, and mitochondrial damage. Myricetin, a natural flavonoid present in many fruits and vegetables, has demonstrated antioxidant and anti-inflammatory activities, making it a potential protective agent against such toxicity.

Methods: This study aimed to evaluate the protective effects of myricetin on Dox-induced liver damage in rats. Thirty-six male Sprague-Dawley rats were divided into six groups: a negative control, a Dox-only group (20 mg/kg, given intraperitoneally on day 10), a myricetin-only group (20 mg/kg, dissolved in corn oil, given orally for 10 days), high-dose (HD) myricetin + Dox (20 mg/kg), low-dose (LD) myricetin + Dox (10 mg/kg), and corn oil control. Biochemical, hematological, oxidative, and histological parameters were evaluated 24 h after Dox injection.

Results: Dox increased serum alanine transaminase (75.6 ± 3.2 U/L), aspartate transaminase (237.6 ± 15.3 U/L), alkaline phosphatase (491.3 ± 16.4 U/L), liver-to-body weight ratio (4.38 ± 0.08%), total oxidant status (TOS, about two-fold compared to the control), and TNF-α (9.94 ± 0.82 U/mL), while decreasing total antioxidant capacity (T-AOC) by 35.2%, and bile acids by 24.0%. Myricetin coadministration, especially at higher doses, significantly reversed these changes. Histopathological evaluation confirmed myricetin's hepatoprotective effect, showing attenuation of hepatocellular degeneration, sinusoidal congestion, and inflammatory infiltration.

Conclusion: Myricetin demonstrated protective effects against Dox-induced liver damage through its antioxidant and anti-inflammatory properties. Further research is warranted.

Background: The present investigation assessed the potential ameliorating effect of zinc oxide resveratrol nanoparticles against Levofloxacin-induced liver damage in rats.

Methods: Fifty adult Wistar rats were split up into five groups at random. (n = 10). GI, (control): was orally gavaged with distilled water; G II (LFX): was orally given levofloxacin (LFX) (40 mg/kg BW). G III was orally administered zinc oxide resveratrol nanoparticles (Zn- RSV) (20 mg/kg BW). G IV: was given Zn-RSV as GIII and LFX as GII simultaneously (LFX + Zn-RSV). GV: was given LFX as GII and zinc oxide (20 mg/kg BW) (LFX + Zn). All treatments were given every other day for two months.

Results: Administration of zinc oxide resveratrol nanoparticles (Zn-RSV NPs) significantly mitigated levofloxacin (LFX)-induced hepatotoxicity in rats. Compared to LFX-treated groups through improved liver function via lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine levels. Also, reduced oxidative stress markers, decreased malondialdehyde (MDA) and nitric oxide (NO) levels in hepatic tissue and enhanced antioxidant defenses, increased superoxide dismutase (SOD) and catalase activities, restoring them to near-normal levels. Modulated apoptosis: Downregulated pro-apoptotic BAX expression and upregulated anti-apoptotic Bcl-2 expression, promoting cell survival. Zn-RSV NPs alleviated histopathological changes through mitigated LFX-induced degenerative and necrotic changes in hepatic tissue, preserving tissue architecture.

Conclusions: This study revealed that zinc oxide resveratrol nanoparticles modulated levofloxacin-induced hepatic damage by lowering inflammation and oxidative stress while increasing the activity of antioxidant enzymes in rat hepatic tissue.

Background: Parabens (PBs) are associated with an increased risk of breast cancer, yet their underlying molecular mechanisms remain poorly understood. This study aimed to comprehensively elucidate the targets and mechanisms of PBs in breast cancer by integrating network toxicology, bioinformatics, Mendelian randomization (MR), molecular docking, and other complementary methodologies.

Results: Network toxicology analysis identified 2,851 potential PB targets, with 172 significantly linked to breast cancer. Pathway enrichment revealed that PBs predominantly influence the Phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway and the cell cycle pathway. Two-sample MR identified TELO2 as a significant risk factor for both malignant and benign breast cancer (malignant: IVW OR = 1.06, 95% CI: 1.001-1.126, p = 0.047; benign: IVW OR = 1.13, 95% CI: 1.009-1.270, p = 0.034). Bioinformatics analysis demonstrated that TELO2 expression was significantly elevated in breast cancer tissues (p < 0.05) and exhibited high diagnostic accuracy (AUC: 0.803 in TCGA and 0.876 in GSE20685). Furthermore, mediation analysis revealed that modulating natural killer T (NKT) cells significantly mediated the TELO2-breast cancer link, with a mediation proportion of 20.46%. Molecular docking confirmed stable binding interactions between PBs and the TELO2 protein. Moreover, an mRNA-microRNA (miRNA)-long non-coding RNA (lncRNA) regulatory network centered on TELO2 identified 19 miRNAs and 189 lncRNAs as potential regulators of its expression.

Conclusions: Our integrative findings suggest that parabens may exert deleterious effects in the context of breast cancer by specifically targeting the TELO2 gene and its associated regulatory networks and pathways. These findings not only advance our understanding of the environmental drivers of BC but also pave the way for future research aimed at mitigating the disease's health burden through targeted interventions against harmful environmental exposures.