Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats

Ibtissem, Ben Amara; Hajer, Ben Saad; Hakim, Ahmed; Elwej, Awatef; Kallel, Choumous; Boudawara, Ons; Mounir, Zeghal Khaled; Zeghal, Najiba

doi:10.4314/ahs.v17i1.20

Cited by 17 publications

(9 citation statements)

References 23 publications

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“…Additionally, investigators found that AOPPs were significantly increased in the plasma and the liver of methylglyoxal treated rats, and the elevated AOPPs could be significantly reduced by treated with resveratrol and carnosine . In addition to the above‐mentioned studies, an increase in liver AOPPs was also noted in methylthiophanate‐, acrylamide‐ and difenoconazole‐treated rats . Although many studies have referred to the profound effects of AOPPs on the progression of diverse liver damages, there have been few studies investigating the potential mechanisms.…”

Section: Data Sourcesmentioning

confidence: 99%

Advanced oxidation protein products play critical roles in liver diseases

Zhao

Zhang

Ouyang

et al. 2019

Eur J Clin Investigation

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There is a complex oxidant and antioxidant system that maintains the redox homoeostasis in the liver. While suffering from exogenous or endogenous risk factors, the balance between oxidants and antioxidants is disturbed and excessive reactive oxygen species are generated, resulting in oxidative stress. Oxidative stress is prevalent in various liver diseases and is thought to be involved in their pathophysiology. Advanced oxidation protein products are generated under conditions of oxidative damage and are newly described protein markers of oxidative stress. Previous studies have underscored the universal pathogenic roles of oxidation protein products in various diseases. However, investigations into how these products participate in the development of liver diseases have been superficial and insufficient. In this review, we highlight the current understanding of the roles of advanced oxidation protein products in liver disease pathogenesis and the underlying mechanisms. Moreover, we summarize the current studies on advanced oxidation protein products in infectious and noninfectious, acute and chronic liver diseases. Different strategies for targeting these advanced oxidation protein products and future perspectives, which may pave the way for developing new therapeutic strategies, will also be discussed here.

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Section: Data Sourcesmentioning

confidence: 99%

Advanced oxidation protein products play critical roles in liver diseases

Zhao

Zhang

Ouyang

et al. 2019

Eur J Clin Investigation

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“…The overproduction of oxygen free radicals can lead to redox alterations through the disturbance of the activity of enzymes that are involved in the oxidative stress situation (Nesnow et al, 2011; Sureshbabu et al, 2015). In this context, many studies have shown that oxidative stress leading to the induction of ROS production is a possible mechanism of pesticide toxicity (Ben Amara et al, 2017; Hamdi et al, 2019). The current study demonstrated that all three doses of CuQ altered GSH and MDA levels, and antioxidant enzymes such as SOD, CAT, GPx, and GST in both kidney and liver of treated animals compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Lipid peroxidation and changes in major antioxidant markers in copper quinolate fungicide-exposed rats

Baali,

Kirane-Amrani,

Tichati

et al. 2023

Toxicol Ind Health

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The present study investigated the toxic effects of sub-chronic exposure to copper quinolate (CuQ) fungicide on liver and kidney function. Twenty-four adult male Wistar rats were equally divided into a control group, and three treated groups received, respectively, by oral gavage, three increasing doses of CuQ: 47; 67.1; and 94 mg/kg b.w corresponding, respectively, LD50/100, LD50/70, and LD50/50 daily for 8 weeks. CuQ resulted in a significant increase in the serum enzymatic activity of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the serum levels of urea, creatinine, uric acid, and malondialdehyde, along with a marked decrease in alanine aminotransferase (ALT) activity, and the contents of total protein and albumin compared to those of the control group. Furthermore, glutathione content and the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) decreased significantly in a dose-dependent manner with respect to CuQ. The adverse effects of CuO were supported by the histopathological evaluations of liver and kidney tissues. Conclusively, sub-chronic CuQ exposure was shown to induce kidney and liver oxidative damage and dysfunction.

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“…However, its widespread use is contributing to the gradual emergence of pathogen resistance to such fungicides . Meanwhile, toxic residues produced by methyl-thiophanate also contribute to ever-growing environmental issues and pose potential risks to human health . Therefore, there is an urgent need to develop novel high-efficiency, eco-friendly, and durable fungicides.…”

Section: Introductionmentioning

confidence: 99%

Novel Design of Citral-Thiourea Derivatives for Enhancing Antifungal Potential against Colletotrichum gloeosporioides

Zeng

Zou

Huang

et al. 2023

J. Agric. Food Chem.

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Although much progress has been made in developing botanical fungicides to combat fungal diseases in crops, there remains a great need to improve the efficiency and long-term safety of these fungicides. This study proposes a novel strategy for designing citral-thiourea derivatives that feature such desirable properties. The motivation of the work herein was to enhance the antifungal activity of citral against C. gloeosprioides by exploiting the synergistic effect that arises from combining citral and thiourea compounds, thereby producing citral-thiourea derivatives that exhibit good long-term safety. The results revealed that the generated compounds e1, e3, e6, e18, and g showed remarkable antifungal activities against C. gloeosprioides, with corresponding EC50 values reaching 0.16, 1.66, 1.37, 4.76, and 4.60 mg/L, respectively, showing that the compounds significantly outperformed both the positive control kresoxim-methyl and the commercially available fungicide carbendazim. Furthermore, compound g showed stronger protective efficacy against C. gloeosprioides than carbendazim on mango fruit at 25 mg/L. Investigating the preliminary structure–activity relationship (SAR) of the compounds also revealed that the citral-thiourea derivatives exhibited higher antifungal activities against C. gloeosprioides compared to citral and thiourea compounds. This reinforcement of antifungal activity observed in the derivatives was found to be attributable to the two characteristics of low molecular size and the presence of a fluorine atom in the meta-position of the benzene ring. Beyond this, it was determined from QSAR that two molecular descriptors (the Kier–Hall index (order 3) and Tot dipole of the molecules) were negatively related to the antifungal activity of the citral-thiourea derivatives, while one other (the maximum resonance energy of a C–H bond) was positively related to their antifungal activity. More importantly, the citral-thiourea derivatives with high antifungal activities (i.e., compounds e1, e3, e6, e14, e15, e18, and g) exhibited negligible cytotoxicity to LO2 and HEK293T cell lines. The antifungal mechanism of the generated citral-thiourea derivatives was investigated by scanning electron microscopy (SEM) and relative conductivity. The derivatives were found to affect mycelial morphology and increase fungal cell membrane permeability, thereby resulting in the destruction of fungal cell membranes. These promising results provide novel insights into the study and potential application value of citral-thiourea derivatives as high-efficiency antifungal agents against C. gloeosprioides.

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Oxidative stress and histopathological changes induced by methylthiophanate, a systemic fungicide, in blood, liver and kidney of adult rats

Cited by 17 publications

References 23 publications

Advanced oxidation protein products play critical roles in liver diseases

Advanced oxidation protein products play critical roles in liver diseases

Lipid peroxidation and changes in major antioxidant markers in copper quinolate fungicide-exposed rats

Novel Design of Citral-Thiourea Derivatives for Enhancing Antifungal Potential against Colletotrichum gloeosporioides

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