Abstract
Objective: Roundup (RUP) is a prominent utilized worldwide herbicide. Possible toxicity of RUP is a considerable debate. We studied the possible mode of RUP cytotoxicity and the antitoxic effects of Eucalyptus camaldulensis (EUC) in male of Bufo regularis.
 Methods: We were analyzed EUC extract scavenging activity and determined the bioactive compounds. In addition, we measured the lipid peroxidation (LPO), histopathological changes, and gene expression in the liver. Frogs were divided into negative control, EUC, RUP, and combined RUP and EUC treated (RUP+EUC) groups. Data were represented as mean±SD and considered statistically significant when p<0.05.
 Results: Treatment of animals with RUP increased LPO and numerous pathological changes with an increased number of melanomacrophages (MMCs). In addition, RUP-treated group revealed downregulation of different genes associated with immunity and mitochondrial activity. On the other side, RUP+EUC-treated group showed restoration of the normal hepatic structure and ultrastructural integrity for a considerable extent. The current study evidenced immune system dysregulation through recombinant activating gene 1 downregulation and overexpression of CX chemokine receptor type-4 and cytochrome c oxidase subunit I.
 Conclusion: The current data represent a direct evidence for the toxicity of RUP that experimentally verified by the histopathological changes, elevated LPO, and imbalanced gene expression. Moreover, aggregation of MMCs pointed to the faced immunological challenges due to RUP toxicity. We are emphasizing that uncontrolled use of RUP is potentially hazardous to the living organisms and man. The application of natural antagonists such a plant extract (e.g., EUC) can reduce biological toxicity.
Highlights
Pesticides are typically used as insecticides, algaecides, and herbicides [1]
Determination of bioactive secondary metabolites and phytochemical screening using gas chromatography–mass spectrometry (GC-MS) analysis The Eucalyptus camaldulensis (EUC) methanolic extract revealed rich contents of flavonoids approximately 453.67±36 mg QE/g extract and polyphenols 329.12±12.1 mg GAE/g extract (Fig. 2)
Its sensitivity to environmental hazardous chemicals is extraordinary, to herbicides which have been implicated as a main cause of subsidizing in a considerable decrease of amphibians [17]
Summary
Pesticides are typically used as insecticides, algaecides, and herbicides [1]. Herbicides undoubtedly provoke a substantial increase in the agriculture welfare and escalate the yield of economic crops, which lowering hunger. They commonly endure in the agricultural areas for prolonged periods, showing various physiological side effects to human and pets [2]. Survival rate of modern amphibians directly influenced by herbicides suppresses their disease fighting ability and severely inhibits larval progress. As well, it changes morphology and physiology and inevitably provokes DNA mutations [5]
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