No abstract

Sonawane et al.: Epididymal Toxicity Associated with Vincristine Vincristine, a major player in front line combination chemotherapy of cancer reduces testosterone levels contributing to reproductive toxicity. Much is known about testicular toxicity of vincristine as compared to its effect on epididymis; hence, the present study aimed to evaluate the epididymal toxicity associated with vincristine treatment, which also contributes to the overall reproductive toxicity associated with vincristine. Vincristine was intraperitoneally injected to adult male Wistar rats of proven fertility with a dose of 40 mg/kg/day dissolved in 0.5 ml of physiological saline for 30 days. The epididymal weight was found to be unaltered after treatment whereas sperm count was reduced signifi cantly. Signifi cant changes were noted in ion concentrations of cauda and caput of epididymis with changes in protein profi le of the tissue, sperm and luminal protein from cauda and caput region, which plays a signifi cant role in sperm maturation and sperm transport. Infertility associated with vincristine could be attributed to its effects on various epididymal proteins involved in sperm protection and various stages of sperm development such as cytoplasmic extrusion and membrane stabilization, which had contributed to the abnormal sperm count and impaired function.

AIDS (Acquired immunodeficiency syndrome) is one of the chronic and potentially life-threatening epidemics across the world. Hitherto, the non-existence of definitive drugs that could completely cure the Human immunodeficiency virus (HIV) implies an urgent necessity for the discovery of novel anti-HIV agents. Since integration is the most crucial stage in retroviral replication, hindering it can inhibit overall viral transmission. The 5 FDA-approved integrase inhibitors were computationally investigated, especially owing to the rising multiple mutations against their susceptibility. This comparative study will open new possibilities to guide the rational design of novel lead compounds for antiretroviral therapies (ARTs), more specifically the structure-based design of novel Integrase strand transfer inhibitors (INSTIs) that may possess a better resistance profile than present drugs. Further, we have discussed potent anti-HIV natural compounds and their interactions as an alternative approach, recommending the urgent need to tap into the rich vein of indigenous knowledge for reverse pharmacology. Moreover, herein, we discuss existing evidence that might change in the near future. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00203-023-03461-8.

Vincristine is major player in front line

Chlorination is a widely used process for disinfecting drinking water, but the emergence of chlorine-resistant bacteria has become a significant concern. While previous research has focused on identifying chlorine-resistant organisms, there has been limited investigation into the mechanisms behind chlorine resistance. Some bacterial isolates that display resistance to chlorine treatment may protect themselves using various mechanisms, including biofilm production, antibiotic resistance, horizontal transfer of antibiotic resistance genes, or producing antioxidant enzymes. Given that chlorination employs hypochlorous acid (HOCl), which is an extremely potent oxidizing agent, the most critical mechanism to investigate is antioxidant enzymes. This study investigated the antioxidant profile of eight chlorine-resistant isolates (three of the Serratia sp. and five of the Acinetobacter) after chlorine exposure. The profiles, both between and within species, were noticeably different. Among the isolates, Acinetobacter junii NA 3-2 showed a significant increase in the specific activity of superoxide dismutase, catalase, and ascorbate peroxidase after exposure to 20 ppm chlorine. In the guaiacol peroxidase (GPX) assay, only isolates belonging to Serratia marcescens showed GPX activity, and Serratia marcescens 3929-1 showed significant increase after exposure to 20 ppm of chlorine. None of the isolates belonging to Acinetobacter spp. showed GPX activity. Additionally, almost all control samples exhibited some enzyme activity, which may explain their survival against chlorine treatment in reservoirs. Principal component analysis revealed no strain-dependent similarities, while the balance of scavenging enzymes changed, as demonstrated in the heat map. Thus, this study suggests that antioxidant enzymes may be one mechanism of protection for some bacterial species against oxidative stress from chlorination, resulting in chlorine resistance. Understanding the mechanism of chlorine resistance is critical to identifying potential solutions. This study highlights the need to consider more modern approaches to disinfecting drinking water.