Extensive uses of silver nanoparticles (Ag NPs) in different industries result in exposure to these nanoparticle imperatives in our daily lives. Resveratrol is found in many plants as a natural compound. The present study aimed to estimate the renal toxic effects of Ag NPs in adult male albino rats and the underlying relevant mechanisms while studying the possible role of resveratrol in ameliorating these effects. Thirty adult albino rats were split into 5 groups; control, vehicle, resveratrol (30 mg/kg), Ag NPs (300 mg/kg), and resveratrol + Ag NPs groups. The treatments were given orally for 4 weeks. Ag NPs group displayed a reduction in kidney weight ( absolute and relative), excess in urinary levels of kidney injury molecule, neutrophil gelatinase-associated lipocalin, cystatin, and blood kidney biomarkers (creatinine, urea, and potassium), increases in oxidative stress markers with the reduction in antioxidant markers, and decreases in serum sirtuin 1(SIRT1) level. Upregulation of interleukin 1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 gene expressions with downregulation of nephrin and podocin gene expressions in renal tissues were also observed. These changes were associated with histological alterations of the glomeruli and tubules, and increased area percentage of collagen fiber. A significant increase in the optical density of transforming growth factor-beta 1 and claudin-1 immunostaining was detected in the Ag NPs group when compared to other groups. All these changes were alleviated by the usage of resveratrol through its anti-oxidant, anti-inflammatory, and activation of SIRT1 recommending its use as a renoprotective agent.

Introduction: Diethyl nitrosamine (DEN), a known carcinogen, has been used for validating the RasH2 and P53 transgenic models in chemical testing and has been shown to enhance primary liver tumor growth in the ATT-Myc transgenic mouse model of liver cancer. Material and Methods: to better understand the mechanism of hepatocellular carcinoma acceleration following DEN, BHT and vehicles treatments in ATT-Myc, transgenic and non-transgenic, mice. We employed an exon array, RT-PCR, Western blotting, and IHC to investigate the complex interplay between the c-Myc transgene and other growth factors in treated mice versus control transgenic and non-transgenic mice. Results: Notably, DEN treatment induced a 12-fold increase in c-Myc expression compared to non-transgenic mice. Furthermore, tumor growth in the DEN group was strongly associated with increased proliferation of transformed or carcinogenic hepatocytes, as evidenced by proliferative cell nuclear antigen and bromodeoxyuridine expression. Internally, the loss of c-Met signaling, enriched transcription factors, and the diminished expression of antioxidants, such as superoxide dismutase (SOD1) and NRF2, further enhanced c-Myc-induced liver tumor growth as early as four months post-DEN treatment. Discussion: Extensive tumor growth was observed at 8.5 months, coinciding with the downregulation of tumor suppressors such as p53. In contrast, at these time points, ATT-Myc transgenic mice exhibited only dysplastic hepatocytes without tumor formation. Additionally, the antioxidant butylated hydroxytoluene maintained c-Met expression and did not promote liver tumor formation. Conclusions: the persistent upregulation of c-Myc in the ATT-Myc liver cancer model, at both the gene and protein levels following DEN treatment inhibited the ETS1 transcription factor, further exacerbating the decline of c-Met signaling, SOD1, and NRF2. These changes led to increased reactive oxygen species production and promoted rapid liver tumor growth.

purpose: Busulfan is an antineoplastic drug that produces pulmonary fibrosis. This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.Methods: Twenty-four adult male rats were divided into four groups: control, α-lipoic acid (ALA), busulfan, and busulfan plus α-lipoic acid. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA were assessed using qRT-PCR.Results: administration of ALA significantly ameliorated BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.Conclusion: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

The journal retracts and amends the authorship list of the article titled “ATT-Myc Transgenic Mouse Model and Gene Expression Identify Genotoxic and Non-Genotoxic Chemicals That Accelerating Liver Tumor Growth in Short-Term Toxicity”