Endocrine disruptive toxicity of cypermethrin in Labeo catla: Involvement of genes and proteins related to the HPG axis.

Cypermethrin (CYP) is a synthetic pyrethroid abundantly used in agriculture and aquaculture. It is an established potent endocrine disruptor to fish, yet the molecular mechanism behind its reproductive toxicity remains unclear. In this study, fish Labeo catla (Catla) was exposed to environmentally relevant concentration of CYP (0.7 µg/L) and 0.14 µg/L for 30 days. The changes in circulating sex steroids, genes, and hormones linked to the hypothalamic-pituitary-gonadal (HPG) axis, stress response and associated histological alterations were studied. Significant decline (P < 0.05) in serum 17 beta (ß) estradiol (E2), 11 ketotestosterone (11-KT), and brain (FSH and GnRH) were observed in 0.7 µg/L dose of CYP. These effects may be due to the down-regulated expression of the upstream genes of the HPG axis i.e. Kiss 1 and Kiss 2, which further downregulates the expression of the GnRH gene. The decreased level of E2 and 11-KT also affects the vitellogenin (Vtg) gene expression, reducing the production of Vtg, a crucial protein for ovarian development. Principal component analysis (PCA) revealed the relationship between CYP and the biosynthesis of sex steroids. The toxic effect of CYP was also visible in antioxidant enzyme assay and related histological alterations. Overall, the study elucidated that long-term exposure to CYP, even at an environmentally relevant dose, may affect reproductive potential and fish recruitment. The study provides important insights into molecular mechanisms underlying CYP-induced endocrine disruption in fish, and it also raises questions about CYP's potential toxicity at environmentally relevant concentration in terms of understanding ecological risk.

Emerging contaminant triclosan incites endocrine disruption, reproductive impairments and oxidative stress in the commercially important carp, Catla (Labeo catla): An insight through molecular, histopathological and bioinformatic approach.

Triclosan (TCS), a broad-spectrum antimicrobial agent is ubiquitous in aquatic ecosystems; however, the mechanisms regarding TCS-induced reproductive toxicity in the teleost still remains uncertain. In this context, Labeo catla were subjected to sub-lethal doses of TCS for 30 days and variations in expression of genes and hormones comprising the hypothalamic-pituitary-gonadal (HPG) axis along with alterations in sex steroids were evaluated. Moreover, manifestation of oxidative stress, histopathological alterations, in silico docking and the potential to bioaccumulate were also investigated. Exposure to TCS may lead to an inevitable onset of the steroidogenic pathway through its interaction at several loci along the reproductive axis: TCS stimulated synthesis of kisspeptin 2 (Kiss 2) mRNAs which in turn prompts the hypothalamus to secrete gonadotropin-releasing hormone (GnRH), resulting in elevated serum 17ß-estradiol (E2) as a consequence; TCS exposure increased aromatase synthesis by brain, which by converting androgens to oestrogens may raise E2 levels; Moreover, TCS treatment resulted in elevated production of GnRH and gonadotropins by the hypothalamus and pituitary, respectively resulting in the induction of E2. The elevation in serum E2 may be linked to abnormally elevated levels of vitellogenin (Vtg) with harmful consequences evident as hypertrophy of hepatocytes and increment in hepatosomatic indices. Additionally, molecular docking studies revealed potential interactions with multiple targets viz. Vtg and luteinizing hormone (LH). Furthermore, TCS exposure induced oxidative stress and caused extensive damage to tissue architecture. This study elucidated molecular mechanisms underlying TCS-induced reproductive toxicity and the need for regulated use and efficient alternatives which could suffice for TCS.

Antibacterial properties and in silico modeling perspective of nano ZnO transported oxytetracycline-Zn2+ complex [ZnOTc]+ against oxytetracycline-resistant Aeromonas hydrophila.

Emergence of antibiotics resistance has threatening consequences not only for human health but also for animal health issues in agriculture. Several animal pathogenic bacteria have developed antibiotic resistance and managing same has tremendous cost repercussions and may lead to total harvest loss. Hence in the present study, efforts are made to revitalize an old antibiotic molecule, oxytetracycline (OTc), through nanodelivery approaches using zinc oxide nanoparticles (nZnO) to confront OTc resistant fish pathogenic bacteria Aeromonas hydrophila. OTc was impregnated in nZnO through in situ precipitation method to develop OTc loaded ZnO nanoparticles (OTc@nZnO) with average size of 99.42 nm. Spectroscopic investigation of same revealed complexation of Zn2+ with amide and aromatic carbonyl moieties of OTc [ZnOTc]+. The complex performed better against A. hydrophila with 7-15 mm inhibition zone as compared to nil for bare OTc at same dose. OTc also showed MIC of 150 µg ml-1 and for OTc@nZnO it was 7.02 µg ml-1 with faster killing rate (k, -0.95). In silico docking simulation suggest that [ZnOTc]+ had low binding affinity (LBE > -5.00 kcal mol-1) toward TetR(E) and TetA(E) proteins of A. hydrophila as compared to OTc (LBE < -8.00 kcal mol-1). This study postulates that [ZnOTc]+ released from OTc@nZnO can escape TetR(E) and TetA(E) resistance proteins and bind at 30S ribosomal subunit with high affinity (<-11.00 kcal mol-1) to exert antibacterial properties. In the recent scenario of recurrent antimicrobial resistance, the develop antibiotic-nanocomposites could come out as potential solution, however further study is required for its feasibility for use in animal health care.