FNT has different negative effects on environmental area and human beings. Therefore, determination of residues of FNT in different matrixes is a very important subject to preserve environment and public health (Bolat et al. 2018). It has been observed that organophosphorus pesticides can induce some degenerative changes and negative effects primarily on the kidney, liver, and other organ systems in studies on various types of experimental animals (Khan 2006; Galal et al. 2019).
Oxidative stress is a situation where the balance between the oxidant and antioxidant systems in the cell is disrupted and oxidants increase. The pathogenesis of many diseases occurs due to oxidative stress (Mondal et al. 2021a; Bahar and Eraslan 2023). Lipid peroxidation (LPO), primarily an important consequence of oxidative damage, is a condition that damages the cell membrane caused by the increase of cellular free oxygen radicals. MDA, one of the most important compounds resulting from lipid peroxidation, is occurs by the peroxidation of polyunsaturated fatty acids in the cell membrane (Mondal et al. 2021a). The increase in FNT in this study is a proof that it causes cell damage. Simultaneously, the MDA level, which increases the toxicity induced by xenobiotic, reacts with DNA, RNA and proteins in cells and probably may causes liver and kidney tissue damage.
Among the antioxidant enzymes, GSH-Px, SOD, and GST are the first defense systems against oxidative injury (El-Shenawy 2010). In previous studies, researchers frequently used GST, CAT, SOD, and GPx antioxidant enzymes to detect cellular oxidative damages (Bas and Kalender 2016; Kalender et al. 2015). SOD converts superoxide anion (O− 2) to hydrogen peroxide (H2O2), while CAT and GPx convert H2O2 into molecular oxygen and water (Othmene et al. 2020). Glutathione (GSH) is known as an important antioxidant that takes part in many reactions within the cell. Glutathione collects and conjugates endogenously formed electrophiles formed during lipid peroxidation. GST participates in the reduction of hydrogen peroxidase (Goel et al. 2005). GST is known to play a role in detoxification and inactivation of toxic plant allelochemicals and insecticides (Francis et al. 2005). Declined GSH-Px and GST activities may be caused by the depletion of GSH which is used a substrate for both of the enzymes. Previous studies noted the decrease in these enzymes during the liver damage induced by OP (Milosevic et al. 2018). The enzyme inhibition seen in this study may be due to the damage of FNT to the structures involved in the antioxidant enzyme system.
Galal et al. (2019) found that an important improvement an oxidative stress biomarker in renal, hepatic and brain tissue of FNT-intoxicated rats. Milosevic et al. reported a decrease in SOD, CAT, GSH-Px, and GST activities in the FNT-treated group (Milosevic et al. 2018). Similarly, antioxidant enzyme activity decreases due to the toxic effect of FNT on the cell.
AChE is an enzyme that eliminates the neurotransmitter acetylcholine (ACh) into choline and acetic acid. Oral toxicity of FNT produced a marked reduction in AChE activity in the liver and kidney tissue (Alam et al., 2019). Excessive suppression of AChE activity causes the accumulation of the neurotransmitter ACh and the effective stimulation of postsynaptic cholinergic receptors, changing postsynaptic cell function, and cholinergic stimulant (Galal et al. 2019). Apart from its ability to facilitate fast neuronal communications between different neuronal sites in the nervous system of vertebrates, ACh system is broadly localized in the other non-neuronal sites such as endothelial tissues, immunological cells, muscles and reproductive organs (Mega et al. 2022). In this study, it was shown that FNT inhibited AChE. This led to a decrease in the enzyme level because FNT caused inhibition the by binding to the enzyme. In agreement with previous pesticide studies (Mega et al. 2022), FNT exposure was associated with increased liver and kidney AChE activity thereby resulting in increased Ach mediated organ damage. However, gallic acid treatment significantly attenuated the effect of FNT on ACh activity.
Histopathology could be used as a keeping track of environmental pollutions or look at specific cellular response in the key organs. Previous studies have shown that organophosphates lead to histopathological changes in many tissues (Othmene et al. 2020, Uzunbayir and Apaydin 2021). In this study, we observed that the FNT induction caused liver and kidney tissue damages. One of the main organs affected by toxic substances is the kidneys, especially the proximal tubules seem to be more affected (Mosa et al. 2019). The liver is mainly responsible for the first detoxification of toxic substances and has the main role in metabolism in terms of energy levels. As a result, it is exposed to many free radical effects (Mondal et al. 2021a). When mice were given FNT, abnormal size and shape of hepatic cells and tubular vascular degeneration and lumen dilatation of kidney cells were observed (Somia et al., 2012). Pesticides produce harmful effects on many organs (Wahed et al. 2019; Bahar and Eraslan 2023). Previous studies have shown that xenobiotic induces renal toxicity due to the production of oxygen free radicals such as H2O2 and O2_. While these free radicals cause damage to the membranes of the tubule cells, they also disrupt the structure of the glomerular basement membrane (Savin et al. 1985; Martınez- Salgado et al. 2002; Zheng et al. 2022). Inflammation, oxidative damage, and cell death are the main mechanisms of tissue damage and organ dysfunction (Mittal et al. 2014; Nasiri et al. 2021; Tekeli et al. 2023), which are well supported by our results. Therefore, increasing serum levels of creatinine, urea, uric acid, and BUN in our study seems reasonable due to the reduced filtration rate.
Changes in liver function upon acute or chronic exposure to toxicants have been reported (Gali et al. 2023). Parameters such as ALP, ALT, AST, and LDH are indicators of liver damage. Additionally, the measurement of serum uric acid and creatinine levels is important for the evaluation of both kidney and liver diseases (Elkhadragy and Moneim 2017; Bas et al. 2021; Mondal et al. 2021a). The latest studies have shown that the improvement in ALT, ALP, AST leads to serious injury in the vital organs, which causes enzymes to enter the blood (Laghari et al. 2020; Uzunhisarcıklı et al. 2021; Aslanturk and Kalender 2022). This may be the cause of the damage to the liver tissue. ALT and AST are enzymes that are involved in transamination reactions. Especially in the case of necrosis, which causes cellular destruction, an increase in the serum number of these enzymes occurs (Wahed et al. 2019; Mondal et al. 2021a; Uzunhisarcıklı et al. 2021; Aslanturk and Kalender 2022). Because of the cell membrane destruction observed in this study, intracellular enzymes may have leaked into the blood. In addition, it appears that the potent nephroprotective and hepatoprotective activity of GA may be attributed to its high polyphenol and flavonoid contents.
In the present study, FNT-treated rats also exhibited significantly decreases WBC and increases in thrombocyte counts. Several studies have shown that OP insecticides can induce hematological changes in experimental animals (Uzun et al. 2010; Uzun et al. 2013). It is an important blood parameter used in hematology toxicology studies. Some researchers showed that OPs caused polycythemia, neutrophilia, thrombocytosis, hepatic and renal derangement in rats. Thrombocytosis observed in the exposed groups could be due to hepatobiliary disease caused by FNT as revealed in this study, which is in broad agreement with previous reports (Awotunsin et al. 2021). The hematopoietic system is sensitive to many toxins, heavy metals, pesticides. Hematological indices such as red blood cells count, white blood cells count, hemoglobin level, and many other parameters were being used to determinant disease and as indications for alterations during stressful toxic conditions (Donmez et al. 20191).
Antioxidant-rich substances including gallic acid, quercetin, baicalin, vitamins and other natural agents are used to protect against environmental pollutants toxicity (Uzun et al. 2010; Donmez et al. 2019; Tekeli et al. 2023). Gallic acid has many properties such as anti-depressant, anti-bacterial, anticancer, antioxidant, and anti-obesity effects (Mondal et al. 2021b). Some researchers reported that gallic acid was found to be the most predominant phenolic acid in both mango peel and pulp with phytotoxic and insect growth regulatory activities (Shivashankar and Sumatki 2022). In previous studies, gallic acid has been shown to have a therapeutic effect on experimental animal tissues antioxidant enzymes via preventing free radical formation. Researchers showed that GA inhibited ROS formation and lipid peroxidation and attenuated glyoxal-induced renal cytotoxicity (Hashemzaei et al. 2020). The protective activity of GA may have related to the suppression of apoptosis based on the ability of polyphenols and flavonoids to protect against stress-induced apoptosis in the tissues. In this study, it was seen that gallic acid had a healing effect on both liver and kidney parameters which is thought to have had this effect with its cleansing properties.