The research progress on the impact of antibiotics on the male reproductive system.

Antibiotics are extensively utilized in the livestock and poultry industry and can accumulate in animals and the environment, leading to potential health risks for humans via food and water consumption. Research on antibiotic toxicity, particularly their impact as endocrine disruptors on the male reproductive system, is still in its nascent stages. This review highlights the toxic effect of antibiotics on the male reproductive system, detailing the common routes of exposure and the detrimental impact and mechanisms of various antibiotic classes. Additionally, it discusses the protective role of food-derived active substances against the reproductive toxicity induced by antibiotics. This review aims to raise awareness about the reproductive toxicity of antibiotics in males and to outline the challenges that must be addressed in future research.

Targeted Detoxification of Aflatoxin B1 in Edible Oil by an Enzyme-Metal Nanoreactor.

Mycotoxin contamination is an important issue for food safety and the environment. Removing mycotoxins from food without losing nutrients and flavor components remains a challenge. In this study, a novel strategy was proposed for the targeted removal of aflatoxin B1 (AFB1) from peanut oil using an amphipathic enzyme-metal hybrid nanoreactor (PL-GOx-Fe3O4@COF) constructed with covalent organic frameworks (COFs) which can selectively adsorb AFB1. Due to the confined space provided by COFs and the proximity effect between GOx and Fe3O4, the detoxification of AFB1 is limited in the nanoreactor without affecting the composition and properties of the oil. The detoxification efficiency of AFB1 in the chemoenzymatic cascade reaction catalyzed by PL-GOx-Fe3O4@COF is six times higher than that of the combination of free GOx and Fe3O4. The AFB1 transformation product has nontoxicity to kidney and liver cells. This study provides a powerful tool for the targeted removal of mycotoxins from edible oils.

Ciprofloxacin and enrofloxacin can cause reproductive toxicity via endocrine signaling pathways.

Ciprofloxacin (CIP) and enrofloxacin (ENR) are veterinary antibiotics commonly utilized to treat and prevent animal diseases. Environmental and dietary antibiotic residues can directly and indirectly affect the reproductive development of animals and humans. This article investigated the reproductive toxicity of CIP in male zebrafish, showing that it could decrease the spermatogonial weight and damage the spermatogonial tissue. The sex hormone assays showed that CIP decreased fshb and lhb gene expression and plasma testosterone (T). In addition, transcriptome analysis indicated that the effect of CIP on zebrafish might be related to the endocrine signaling pathways. ENR, which was selected for further study, inhibited mouse Leydig (TM3) and Sertoli (TM4) cell proliferation and caused cell cycle arrest. The sperm concentration, serum luteotropic hormone (LH) and follicle-stimulating hormone (FSH), and T levels decreased in adolescent mice after ENR treatment for 30d in vivo. Hematoxylin and eosin (H&E) staining showed that ENR exposure potentially induced testicular injury, while the real-time quantitative PCR (qPCR) results indicated that ENR inhibited the mRNA expression of key genes in the Leydig cells (cyp11a1, 3ß-HSD, and 17ß-HSD), Sertoli cells (Inhbß and Gdnf) and spermatogenic cells (Plzf, Stra8 and Dmc1). In conclusion, these findings indicated that ENR exposure might influence the development of the testes of pubescent mice.

Combination of oxytetracycline and quinocetone synergistically induces hepatotoxicity via generation of reactive oxygen species and activation of mitochondrial pathway.

Oxytetracycline (OTC) and Quinocetone (QCT) are antimicrobials, whose residues have been found in food and environment. These two are sometimes used simultaneously in livestock and aquaculture, potentially resulting in the simultaneous consumption of multi-antimicrobials by consumers. However, the combined toxic effects of this phenomenon have yet to be addressed. Since the liver is a major target of both OTC and QCT, we tested their hepatotoxic effect using both cell cultures and animal models. Results showed that the QCT (5-25 µM) or OTC (20-100 µM) treatments alone caused dose-dependent reductions in cell numbers, while their combination strongly further enhanced inhibitory effects. Mechanistically, the combination enhanced the generation of reactive oxygen species (ROS) and activated mitochondrial cell death pathways. It also showed that the combination of OTC (800 mg/kg, i.g., 5d) and QCT (5000 mg/kg, i.g., 5d) resulted in significantly enhanced liver toxicity in C57BL/6N mice, the serum alanine transaminase (ALT) and aspartate transaminase (AST) were significantly increased by the OTC/QCT. These findings indicate the necessity of considering the combined toxicity of these two antimicrobials in safety assessments.

The combination of T-2 toxin and acrylamide synergistically induces hepatotoxicity and nephrotoxicity via the activation of oxidative stress and the mitochondrial pathway.

T-2 toxin is a common fungal toxin, which is not only widely found in wheat, barley, corn, and other food crops and their related products, but also in various animal feeds. Acrylamide (ACR) is mainly formed by the free amino acid, asparagine and reducing sugars, such as glucose and fructose, and is commonly found in potato chips, French fries, toast, coffee, and other foods. Therefore, people are highly likely to consume food via their daily diets that are contaminated with both T-2 toxin and ACR. Since liver and kidneys were possible toxic targets of both T-2 toxin and ACR, this study assessed whether combined exposure could increase hepatotoxicity and nephrotoxicity using both cell cultures and animal models. We used L02 and MARC-145 cells and treated with T-2 toxin (5-15 nM) and ACR (1-3 mM) alone or in combination with a fixed ratio of 1:200 (T-2 toxin/ACR). ACR (50 mg/kg, i.g., 5d) and T-2 toxin (5 mg/kg, i.g., 5d) were used to assess the biochemical, proteins and histplogical changes in C57BL/6N mice. Results showed the combination resulted in synergistic cytotoxicity in vitro, while significantly increasing liver and kidney toxicity in vivo. Mechanistically, T-2 toxin decreased Manganese superoxide dismutase expression, while ACR reduced catalase expression. These two mechanisms were converged in response to the combination, leading to enhanced oxidative stress generation. The findings highlighted the necessity to consider the combined toxicity during the safety assessment of these food-borne contaminants.