Molecular insights into the antioxidative and anti-inflammatory effects of P-coumaric acid against bisphenol A-induced testicular injury: In vivo and in silico studies.

This study investigated the protective effects of p-coumaric acid (PCA) against bisphenol A (BPA)-induced testicular toxicity in male rats. The rats were divided into control, BPA, BPA+PCA50, BPA+PCA100, and PCA100 groups. Following a 14-day treatment period, various analyses were conducted on epididymal sperm quality and testicular tissues. PCA exhibited dose-dependent cytoprotective, antioxidant, and anti-inflammatory effects, ameliorating the decline in sperm quality induced by BPA. The treatment elevated antioxidant enzyme activities (SOD, GPx, CAT) and restored redox homeostasis by increasing cellular glutathione (GSH) and reducing malondialdehyde (MDA) levels. PCA also mitigated BPA-induced proinflammatory responses while reinstating anti-inflammatory IL-10 levels. Apoptotic parameters (p53 and p38-MAPK) were normalized by PCA in BPA-treated testicular tissue. Immunohistochemical and immunofluorescent analyses confirmed the cytoprotective and anti-inflammatory effects of PCA, evidenced by the upregulation of HO-1, Bcl-2, and Nrf-2 and the downregulation of the proapoptotic gene Bax in BPA-induced testicular intoxication. PCA corrected the disturbance in male reproductive hormone levels and reinstated testosterone biosynthetic capacity after BPA-induced testicular insult. In silico analyses suggested PCA's potential modulation of the oxidative stress KEAP1/NRF2/ARE pathway, affirming BPA's inhibitory impact on P450scc. This study elucidates BPA's molecular disruption of testosterone biosynthesis and highlights PCA's therapeutic potential in mitigating BPA's adverse effects on testicular function, showcasing its cytoprotective, anti-inflammatory, and hormone-regulating properties. The integrated in vivo and in silico approach offers a comprehensive understanding of complex mechanisms, paving the way for future research in reproductive health and toxicology, and underscores the importance of employing BPA-free plastic wares in semen handling.

The Synthetic Antimicrobial Peptide Derived From Melittin Displays Low Toxicity and Anti-infectious Properties.

The low stability and nonspecific toxicity are the main limiting factors for the clinical applications of melittin (MLT). This study aimed to design and synthesize new analogs of MLT to increase stability, reduce toxicity, and retain their antimicrobial properties against bacterial pathogens. At first, peptide analogs were designed computationally by inducing single mutations in MLT peptides and evaluating their physicochemical properties. The stability of the analogs with the highest scores was determined by Gromacs software. In vitro assays were performed to examine the antimicrobial activity and toxicity of the selected analogs. Two peptide analogs, M1 and M2, were selected based on the SVM score in cell PPD. The M1 analog was created by replacing alanine with leucine on the 15th. The M2 analog was designed by substituting alanine with leucine and isoleucine with arginine at the 15th and 17th positions. According to the Gromacs results, the M2 peptide indicated more stability. RMSD and RMSF results showed no undesirable fluctuations during the 200 ns MD simulation. The MIC and MBC values for the M1 peptide were calculated in a range of 8-128 µg/ml, while the M2 peptide limited the bacterial growth to 32-128 µg/mL. Both peptides indicated less toxicity than natural MLT, based on MTT assay results. The hemolytic activity of the M1 analog was more than M2 at 16 µg/mL concentration. M1 peptide displayed the highest selectivity index against S. aureus and A. baumannii, which were approximately 5.27-fold improvements compared to MLT. In conclusion, we introduced two analogs of MLT with low toxicity, low hemolytic activity, and higher stability, along with retaining antimicrobial properties against gram-negative and positive bacteria.